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Acuna N, Park SY, Le Marchand L, Hébert JR, Boushey C, Wilkens LR, Wu AH, Setiawan VW. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort. Am J Clin Nutr 2023; 117:46-54. [PMID: 36789943 PMCID: PMC10196603 DOI: 10.1016/j.ajcnut.2022.11.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/28/2022] [Accepted: 11/04/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Certain dietary patterns (i.e., low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with the risk of gastric cancer. However, it is unclear whether overall diet quality assessed by predefined indices that consider the complexity of dietary intake is associated with gastric cardia and distal adenocarcinoma. OBJECTIVES To examine the association of a variety of diet indices with the risk of gastric cardia and distal adenocarcinoma and assess whether there are any subgroups that may benefit from better diets to reduce the risk of gastric adenocarcinoma. METHODS Dietary indices of interest included the Alternative Healthy Index (AHEI)-2010, Healthy Eating Index (HEI)-2015, the Dietary Approach to Stop Hypertension, alternate Mediterranean diet (aMED), and the energy-adjusted Dietary Inflammatory Index. RESULTS After an average follow-up time of 19.2 years, there were 836 incident cases of gastric distal adenocarcinoma and 207 cases of gastric cardia adenocarcinoma. We did not observe any significant associations between the dietary indices and gastric cancer for either anatomic site. Among former aspirin users, we observed an inverse association between aMED with distal cancer (HRQ5 vs. Q1: 0.64; 95% CI: 0.33, 1.23; P-trend = 0.03). Never smokers, who showed high-quality diet according to AHEI-2010, exhibited a 40% decreased risk of gastric distal cancer compared with those with the poorest-quality AHEI-2010 diet (HRQ5 vs. Q1: 0.60; 95% CI: 0.41, 0.88; P-trend = 0.08). CONCLUSIONS In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among former aspirin users and never smokers, there could be a reduction of gastric distal adenocarcinoma risk with a higher adherence to a Mediterranean diet.
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Affiliation(s)
- Nicholas Acuna
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Song-Yi Park
- Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, HI, USA
| | - Loïc Le Marchand
- Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, HI, USA
| | - James R Hébert
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Carol Boushey
- Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, HI, USA
| | - Lynne R Wilkens
- Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, HI, USA
| | - Anna H Wu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - V Wendy Setiawan
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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McMahon NF, Brooker PG, Pavey TG, Leveritt MD. Nitrate, nitrite and nitrosamines in the global food supply. Crit Rev Food Sci Nutr 2022; 64:2673-2694. [PMID: 36168920 DOI: 10.1080/10408398.2022.2124949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Inorganic nitrate provided by either nitrate salts or food supplements may improve cardiometabolic health. However, current methods to assess dietary nitrate, nitrite and nitrosamine consumption are inadequate. The purpose of this study was to develop a reference database to estimate the levels of nitrate, nitrite and nitrosamines in the global food supply. A systematic literature search was undertaken; of the 5,747 articles screened, 448 met the inclusion criteria. The final database included data for 1,980 food and beverages from 65 different countries. There were 5,105 unique records for nitrate, 2,707 for nitrite, and 954 for nitrosamine. For ease of use, data were sorted into 12 categories; regarding nitrate and nitrite concentrations in food and beverages, 'vegetables and herbs' were most reported in the literature (n = 3,268 and n = 1,200, respectively). For nitrosamines, 'protein foods of animal origin' were most reported (n = 398 records). This database will allow researchers and practitioners to confidently estimate dietary intake of nitrate, nitrite and nitrosamines. When paired with health data, our database can be used to investigate associations between nitrate intake and health outcomes, and/or exercise performance and could support the development of key dietary nitrate intake guidelines.
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Affiliation(s)
- Nicholas F McMahon
- School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Queensland, Australia
| | - Paige G Brooker
- School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Queensland, Australia
| | - Toby G Pavey
- School of Exercise and Nutrition Sciences, Queensland University of Technology, Kelvin Grove, Queensland, Australia
| | - Michael D Leveritt
- School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Queensland, Australia
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Sekaran A, Dey D, Singh A, Das P. Pathology of Malignant Lesions of the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:699-782. [DOI: 10.1007/978-981-16-6395-6_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Khan NA, Ahmad SN, Dar NA, Masoodi SR, Lone MM. Changing Pattern of Common Cancers in the Last Five Years in Kashmir, India: A Retrospective Observational Study. Indian J Med Paediatr Oncol 2021. [DOI: 10.1055/s-0041-1740047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Introduction Cancer is emerging as a major health problem worldwide. Profile and pattern of cancers vary as per the geographic, ethnic, and sociocultural background of the population. It is imperative to know the change in the pattern of cancer in the population to formulate an effective strategy for its control and management.
Objective To study the changing trends and epidemiological distribution of common cancer types in an ethnic population of Northern India.
Materials and Methods In this retrospective observational study, we audited records of 22,188 patients with histologically documented cancer registered between January 2014 and December 2018 in the regional cancer center of a tertiary care institute in North India. For all identified patients, medical records were reviewed for demographic information (age of diagnosis, sex, type of cancer, and select risk factors). The data analysis was done using IBM SPSS Statistics for Windows from IBM Corp. Data were expressed as frequencies with percentages. The incidence and trends were depicted through tables, and line diagrams were used to show the changes (if any) over the last 5 years.
Results The most common cancer reported in the last 5 years was lung cancer, overall (10.6%; 95% confidence interval [CI], 10.2–11.0) as well as in men (14.8%; 95% CI, 14.2–15.4) and breast cancer in females (13.5%; 95% CI, 12.8–14.2). The top five cancers reported at our center were lung (10.6%), esophagus (9.1%), stomach (9.0%), breast (6.0%), and colon (3.8%). Compared with that, the top five cancers reported from our center in 2012 were esophagus and gastroesophageal junction (17.2%), lung (11.9%), stomach (9.7%), colorectal (7.1%), and breast (6.5%). Prostate cancer was reported in 3.4% of cases, which was much higher than that reported in 2012 (1.7%). Surprisingly, thyroid cancer (6.4%) was the fourth commonest cancer reported in females, while it did not figure in the top 10 cancers in the 2012 report. Expectantly, cervix cancer did not figure among the top 10 cancers in women.
Conclusion There is a change in the pattern of cancers. Lung and breast have emerged as the most commonly occurring cancers in men and women, respectively, whereas there was a slight downward trend in the incidence of esophageal cancer.
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Affiliation(s)
- Nazir Ahmad Khan
- Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, Jammu and Kashmir, India
| | - Syed Nisar Ahmad
- Department of Medical Oncology, Sheri Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, Jammu and Kashmir, India
| | - Nazir Ahmad Dar
- Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, Jammu and Kashmir, India
| | - Shariq Rashid Masoodi
- Department of Endocrinology, Sheri Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, Jammu and Kashmir, India
| | - Mohammad Maqbool Lone
- Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, Jammu and Kashmir, India
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A decade in unravelling the etiology of gastric carcinogenesis in Kashmir, India – A high risk region. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue. MEDICINES 2020; 7:medicines7040018. [PMID: 32252407 PMCID: PMC7235778 DOI: 10.3390/medicines7040018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 03/26/2020] [Accepted: 03/28/2020] [Indexed: 12/13/2022]
Abstract
Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.
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Liu AH, Bondonno CP, Russell J, Flood VM, Lewis JR, Croft KD, Woodman RJ, Lim WH, Kifley A, Wong G, Mitchell P, Hodgson JM, Blekkenhorst LC. Relationship of dietary nitrate intake from vegetables with cardiovascular disease mortality: a prospective study in a cohort of older Australians. Eur J Nutr 2018; 58:2741-2753. [PMID: 30238316 DOI: 10.1007/s00394-018-1823-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 09/12/2018] [Indexed: 12/30/2022]
Abstract
PURPOSE Short-term trials indicate inorganic nitrate and nitrate-rich vegetables may have vascular health benefits. However, few observational studies have explored the relationship between nitrate intake and long-term cardiovascular disease (CVD) outcomes. The primary aim of this study was to investigate the association of nitrate intake from vegetables with CVD mortality in a sample of older Australians. METHODS A subgroup of participants without diabetes or major CVD at baseline (1992-1994) were included from the Blue Mountains Eye Study, a population-based cohort study of men and women aged ≥ 49 years. Diets were evaluated using a validated food frequency questionnaire at baseline, 5 years and 10 years of follow-up. Vegetable nitrate intake was estimated using a comprehensive vegetable nitrate database. Cox proportional hazard regression was used to explore the association between vegetable nitrate intake and CVD mortality. RESULTS During 14 years of follow-up, 188/2229 (8.4%) participants died from CVD. In multivariable-adjusted analysis, participants in quartile 2 [69.5-99.6 mg/day; HR 0.53 (95% CI 0.35, 0.82)], quartile 3 [99.7-137.8 mg/day; HR 0.51 (95% CI 0.32, 0.80)], and quartile 4 [> 137.8 mg/day; HR 0.63 (95% CI 0.41, 0.95)] of vegetable nitrate intake had lower hazards for CVD mortality compared to participants in quartile 1 (< 69.5 mg/day). CONCLUSIONS In older Australian men and women, vegetable nitrate intake was inversely associated with CVD mortality, independent of lifestyle and cardiovascular risk factors. These findings confirm a recent report that intake of vegetable nitrate lowers the risk of CVD mortality in older women and extend these findings to older men.
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Affiliation(s)
- Alex H Liu
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia
| | - Catherine P Bondonno
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Joanna Russell
- School of Health and Society, Faculty of Social Sciences, The University of Wollongong, Wollongong, Australia
| | - Victoria M Flood
- Faculty of Health Sciences, The University of Sydney, Sydney, NSW, Australia.,Western Sydney Local Health District, Westmead Hospital, Westmead, NSW, Australia
| | - Joshua R Lewis
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Centre for Kidney Research, Children's Hospital at Westmead, Westmead, NSW, Australia.,School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Kevin D Croft
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia
| | - Richard J Woodman
- Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, SA, Australia
| | - Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Annette Kifley
- Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Germaine Wong
- Centre for Kidney Research, Children's Hospital at Westmead, Westmead, NSW, Australia.,School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Paul Mitchell
- Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Jonathan M Hodgson
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Lauren C Blekkenhorst
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
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DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case-Control Study Outcome from Kashmir, India. Anal Cell Pathol (Amst) 2018; 2018:3806514. [PMID: 30225185 PMCID: PMC6129361 DOI: 10.1155/2018/3806514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 06/03/2018] [Accepted: 06/05/2018] [Indexed: 01/25/2023] Open
Abstract
Coding polymorphisms in several DNA repair genes have been reported to affect the DNA repair capacity and are associated with genetic susceptibility to many human cancers, including gastric cancer. An understanding of these DNA repair gene polymorphisms might assess not only the risk of humans exposed to environmental carcinogens but also their responses to different therapeutical approaches, which target the DNA repair pathway. In the present study, polymorphic variants of two DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in association with gastric cancer susceptibility in the Kashmiri population. A total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were included in the study. The genotyping for XRCC1 and XPD genes was carried out by polymerase chain reaction-restriction fragment length polymorphism. We found that tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49–119.7). However, we did not find any association of polymorphism of XRCC1 Arg399Gln (OR = 1.56; 95% CI: 0.32–7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10–2.19) with GC risk in the study population. The combination of genotypes and gender stratification of XRCC1 and XPD genotypic frequency did not change the results. Consumption of large volumes of salt tea was also not associated with gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln are not associated with the risk of gastric cancer in the Kashmiri population. However, replicative studies with larger sample size are needed to substantiate the findings.
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Zaidi SF. Helicobacter pylori associated Asian enigma: Does diet deserve distinction? World J Gastrointest Oncol 2016; 8:341-350. [PMID: 27096029 PMCID: PMC4824712 DOI: 10.4251/wjgo.v8.i4.341] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 11/23/2015] [Accepted: 01/22/2016] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world’s population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with virulent H. pylori strains, however further affirmation studies are desperately needed to achieve conclusive outcomes.
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Qasim I, Bhat IA, Masoodi KZ, Shah ZA. Role of +405C>G and +936C>T polymorphisms of the vascular endothelial growth factor gene and risk of esophageal cancer in the Kashmiri population. Asian Pac J Cancer Prev 2015; 16:97-101. [PMID: 25640399 DOI: 10.7314/apjcp.2015.16.1.97] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The gene for the vascular endothelial growth factor (VEGF), which promotes angiogenesis and permeability, is polymorphic. The aim of the present study was to evaluate the relationship between +936C>T and +404C>G polymorphism of VEGF with risk of esophageal cancer in the Kashmiri population in India. MATERIALS AND METHODS 150 esophageal cancer patients and 150 unrelated healthy controls were genotyped for two VGEF SNPs (+405C/G, and +936C/T) using DNA extracted from prospectively collected blood samples by the PCR-RFLP method. RESULTS For the VEGF +936C>T polymorphism a significant association of CT and combined CT+TT genotypes was observed with increased risk of esophageal cancer (p=0.021; 0.024). For the +405C>G polymorphism we observed significantly increased frequency of GG genotype in cases as compared to controls and also the +405 GG Genotype was observed to have a two fold risk(OR=2.7356; 95%CI=1.1409- 6.5593; p=0.020). The combined genotypes of GG-CC and GG-CT of +405C>G and +936C>T were found to be significantly associated with increased risk of esophageal cancer (p=0.0376; 0.0099). CONCLUSIONS From the results of the present study a significant association of +936C>T and +405C>G polymorphisms with increased esophageal cancer risk exists in the Kashmiri population.
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Affiliation(s)
- Iqbal Qasim
- Department of Immunology and Molecular Medicine Sheri Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India E-mail : zaff
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Erratum: Salt tea consumption and esophageal cancer: A possible role of alkaline beverages in esophageal carcinogenesis. Int J Cancer 2015; 137:E2-8. [DOI: 10.1002/ijc.29550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Revised: 08/20/2014] [Accepted: 08/21/2014] [Indexed: 11/12/2022]
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Yun YX, Dai LP, Wang P, Wang KJ, Zhang JY, Xie W. Association of polymorphisms in X-ray repair cross complementing 1 gene and risk of esophageal squamous cell carcinoma in a Chinese population. BIOMED RESEARCH INTERNATIONAL 2015; 2015:509215. [PMID: 25710005 PMCID: PMC4331318 DOI: 10.1155/2015/509215] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 11/30/2014] [Accepted: 12/02/2014] [Indexed: 11/17/2022]
Abstract
OBJECTIVES To investigate the association between three single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing 1 gene (XRCC1) and the risk of esophageal squamous cell carcinoma (ESCC) in Chinese population. METHODS A case-control study including 381 primary ESCC patients recruited from hospital and 432 normal controls matched with patients by age and gender from Chinese Han population was conducted. The genotypes of three XRCC1 polymorphisms at -77T>C (T-77C), codon 194 (Arg194Trp), and codon 399 (Arg399Gln) were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP). Unconditional logistic regression model and haplotype analysis were used to estimate associations of these three SNPs in XRCC1 gene with ESCC risk. RESULTS Polymorphisms at these three sites in XRCC1 gene were not found to be associated with risk for developing ESCC; however the haplotype C(codon 194)G(codon 399)C(-77T>C) was significantly associated with reduced risk of ESCC (OR: 0.62, 95% CI: 0.40-0.96) upon haplotype analysis. CONCLUSION These results suggested that the gene-gene interactions might play vital roles in the progression on esophageal cancer in Chinese Han population and it would be necessary to confirm these findings in a large and multiethnic population.
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Affiliation(s)
- Yu-Xia Yun
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
- Department of Immunization Planning, Centers for Disease Control and Prevention of Puyang City, Puyang, Henan 457000, China
| | - Li-Ping Dai
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Peng Wang
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Kai-Juan Wang
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Jian-Ying Zhang
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Wei Xie
- Department of Radiology, The First Affiliated Hospital & Department of Epidemiology, College of Public Health and Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China
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Malakar M, Devi KR, Phukan RK, Kaur T, Deka M, Puia L, Sailo L, Lalhmangaihi T, Barua D, Rajguru SK, Mahanta J, Narain K. p53 codon 72 polymorphism interactions with dietary and tobacco related habits and risk of stomach cancer in Mizoram, India. Asian Pac J Cancer Prev 2014; 15:717-23. [PMID: 24568485 DOI: 10.7314/apjcp.2014.15.2.717] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study was carried out to investigate the interaction of p53 codon 72 polymorphism, dietary and tobacco habits with reference to risk of stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach cancer cases and 210 age, sex and ethnicity matched healthy population controls were included in this study. MATERIALS AND METHODS The p53 codon 72 polymorphism was detected by PCR-RFLP and sequencing. H. pylori infection status was determined by ELISA. Information on various dietary and tobacco related habits was recorded with a standard questionnaire. RESULTS This study revealed that overall, the Pro/ Pro genotype was significantly associated with a higher risk of stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype. In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50; 95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2) among older people (>60 years). However, no such associations were observed in males and in individuals <60 years of age. Smoke dried fish and preserved meat (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR, 4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared to non-consumers. Significant gene-environment interactions exist in terms of p53 codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI, 1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21). CONCLUSIONS In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.
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Affiliation(s)
- Mridul Malakar
- Regional Medical Research Centre, NE Region (Indian Council of Medical Research), Dibrugarh, India E-mail :
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Malik MA, Srivastava P, Zargar SA, Mittal B. Phospholipase C epsilon 1 (PLCE1) haplotypes are associated with increased risk of gastric cancer in Kashmir Valley. Saudi J Gastroenterol 2014; 20:371-377. [PMID: 25434319 PMCID: PMC4271013 DOI: 10.4103/1319-3767.145330] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Accepted: 07/18/2014] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIM Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley. PATIENTS AND METHODS The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant. RESULTS The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea. CONCLUSION These results suggest that variation in PLCE1 may be associated with GC risk in Kashmir Valley.
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Affiliation(s)
- Manzoor A. Malik
- Department of Ocular Biochemistry, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
| | - Priya Srivastava
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
| | - Showkat A. Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
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Dar NA, Bhat GA, Shah IA, Iqbal B, Rafiq R, Nabi S, Lone MM, Islami F, Boffetta P. Salt tea consumption and esophageal cancer: a possible role of alkaline beverages in esophageal carcinogenesis. Int J Cancer 2014; 136:E704-10. [PMID: 25209106 DOI: 10.1002/ijc.29204] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Revised: 08/20/2014] [Accepted: 08/21/2014] [Indexed: 01/26/2023]
Abstract
Salt tea is the most commonly used beverage in Kashmir, India, where esophageal squamous cell carcinoma (ESCC) is the most common cancer. Salt tea is brewed in a unique way in Kashmir, usually with addition of sodium bicarbonate, which makes salt tea alkaline. As little information about the association between salt tea drinking and ESCC was available, we conducted a large-scale case-control study to investigate this association in Kashmir. We recruited 703 histologically confirmed cases of ESCC and 1664 controls individually matched to cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Participants who consumed >1,250 ml day(-1) showed an increased risk of ESCC (OR = 2.60, 95% CIs = 1.68-4.02). Samovar (a special vessel for the beverage preparation) users (OR = 1.77, 95% CIs 1.25-2.50) and those who ate cereal paste with salt tea (OR = 2.14, 95% CIs = 1.55-2.94) or added bicarbonate sodium to salt tea (OR = 2.12, 95% CIs = 1.33-3.39) were at higher risk of ESCC than others. When analysis was limited to alkaline tea drinkers only, those who both consumed cereal paste with salt tea and used samovar vessel were at the highest risk (OR = 4.58, 95% CIs = 2.04-10.28). This study shows significant associations of salt tea drinking and some related habits with ESCC risk.
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Affiliation(s)
- Nazir Ahmad Dar
- Department of Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir, India
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Nganje TN, Hursthouse AS, Edet A, Stirling D, Adamu CI. Assessment of the Health Risk, Aesthetic and Agricultural Quality of Rainwater, Surface Water and Groundwater in the Shale Bedrock Areas, Southeastern Nigeria. ACTA ACUST UNITED AC 2014. [DOI: 10.1007/s12403-014-0136-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Mishra A, Meherotra R. Head and Neck Cancer: Global Burden and Regional Trends in India. Asian Pac J Cancer Prev 2014; 15:537-50. [DOI: 10.7314/apjcp.2014.15.2.537] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Malik MA, Umar M, Gupta U, Zargar SA, Mittal B. Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley. Asian Pac J Cancer Prev 2014; 15:4319-4323. [PMID: 24935391 DOI: 10.7314/apjcp.2014.15.10.4319] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. MATERIALS AND METHODS We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. RESULTS The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. CONCLUSIONS Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India E-mail : ,
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Malik MA, Gupta A, Zargar SA, Mittal B. Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis. Tumour Biol 2013; 34:3049-3057. [PMID: 23765761 DOI: 10.1007/s13277-013-0870-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 05/15/2013] [Indexed: 12/19/2022] Open
Abstract
Genetic alterations in the deleted in colorectal carcinoma (DCC) gene have been a priori reported to associate with metastasis in variety of human cancers. We investigated the association between potentially functional SNPs in DCC and susceptibility to esophageal (EC) and gastric (GC) cancers in Kashmir Valley. We genotyped two SNPs DCC rs714 (A>G) and DCC rs2229080 (C>G) of DCC in 135 EC patients, 108 GC patients, and 195 controls matched by age and sex in Kashmir Valley by polymerase chain reaction-RFLP method. Risk for developing EC and GC was estimated by binary logistic regression by using SPSS. We also performed a meta-analysis on DCC rs714 (A>G) and evaluated the association between the DCC rs714 (A>G) polymorphisms and cancer risk. A significant difference in DCC rs714 (A>G) genotype distribution between EC and GC cases and corresponding control groups was observed (odds ratio (OR) = 1.92; P = 0.03; P-trend = 0.04; false discovery rate (FDR) Pcorr = 0.03: OR = 2.15; P = 0.02; P-trend = 0.01; FDR Pcorr = 0.03). But no such association was observed in DCC rs2229080 (C>G). Further, DCC rs714 (A>G) AA genotype showed significantly increased risk for both gastric squamous cell carcinoma (OR = 5.63; P = 0.02; FDR Pcorr = 0.01) and gastric adenocarcinoma (OR = 2.15; P = 0.02; FDR Pcorr = 0.01). Smoking and salted tea are independently associated with both EC and GC, but gene-environment interaction did not further modulate the risk. Meta-analysis also suggested both independent and overall association of DCC rs714 (A>G) polymorphism with cancer (P = 0.000). In conclusion, genetic variations in DCC rs714 (A>G) modulate risk of EC and GC in high-risk Kashmir population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India
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Li S, Deng Y, You JP, Chen ZP, Peng QL, Huang XM, Lu QH, Huang XL, Zhao JM, Qin X. XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms in esophageal cancer risk: a meta-analysis. Dig Dis Sci 2013; 58:1880-90. [PMID: 23543084 DOI: 10.1007/s10620-013-2569-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 01/06/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. AIM To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis. METHODS Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. RESULTS According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053-1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093-1.624, P = 0.005). CONCLUSIONS Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.
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Affiliation(s)
- Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
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Sameer AS. Colorectal cancer: a researcher’s perspective of the molecular angel’s gone eccentric in the Vale of Kashmir. Tumour Biol 2013; 34:1301-1315. [PMID: 23417859 DOI: 10.1007/s13277-013-0692-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 02/03/2013] [Indexed: 02/06/2023] Open
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NISSAR SANIYA, LONE TUFAILAHMAD, BANDAY MUJEEBZAFAR, RASOOL ROOHI, CHOWDRI NISSARA, PARRAY FAZLQ, ABDULLAH SAFIYA, SAMEER AGASYED. Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study. Oncol Lett 2013; 5:959-963. [PMID: 23426866 PMCID: PMC3576209 DOI: 10.3892/ol.2013.1104] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2012] [Accepted: 07/12/2012] [Indexed: 01/13/2023] Open
Abstract
The aim of this study was to investigate the role of the XRCC1 Arg399Gln polymorphism in the susceptibility of a Kashmiri population to colorectal cancer (CRC). We investigated the genotype distribution of the XRCC1 gene in 130 CRC cases in comparison with that of 150 healthy subjects. There was no direct significant association between the XRCC1 genotypes and CRC; however, the Arg/Gln genotype was associated with an elevated risk of CRC (OR>1.47) and the Gln/Gln variant genotype was associated with an increased risk of CRC in various clinicopathological parameters. This study suggests that the XRCC1 polymorphism is associated with an increased risk of CRC.
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Affiliation(s)
- SANIYA NISSAR
- Departments of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | - TUFAIL AHMAD LONE
- General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | | | - ROOHI RASOOL
- Departments of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | - NISSAR A. CHOWDRI
- General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | - FAZL Q. PARRAY
- General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | - SAFIYA ABDULLAH
- Departments of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Bemina
| | - AGA SYED SAMEER
- Departments of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Bemina
- Department of Biochemistry, Medical College, Sher-I-Kashmir Institute of Medical Sciences, Bemina, Srinagar, Kashmir,
India
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Sameer AS, Parray FQ, Dar MA, Nissar S, Banday MZ, Rasool S, Gulzar GM, Chowdri NA, Siddiqi MA. Cyclin D1 G870A polymorphism and risk of colorectal cancer: a case control study. Mol Med Rep 2013; 7:811-5. [PMID: 23354584 DOI: 10.3892/mmr.2013.1287] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2012] [Accepted: 08/17/2012] [Indexed: 12/11/2022] Open
Abstract
The present study aimed to analyse the role of cyclin D1 A870G polymorphism in modulating the susceptibility to colorectal cancer (CRC) in the Kashmiri population. The genotype distribution of the cyclin D1 gene in 130 CRC cases in comparison with 160 healthy controls was investigated. No direct significant association between cyclin D1 genotypes and CRC was observed; however, the AG and AA genotypes were found to be associated with an increased risk of CRC compared to the GG genotype, with an almost 2-fold increase in OR. This study suggests that the cyclin D1 polymorphism is associated with an increased risk of CRC in the Kashmiri population.
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Affiliation(s)
- Aga Syed Sameer
- Department of Immunology and Molecular Medicine, Sher‑I‑Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
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Malik MA, Zargar SA, Mittal B. Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis. Mol Biol Rep 2012; 39:9095-9104. [PMID: 22736108 DOI: 10.1007/s11033-012-1781-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Accepted: 06/09/2012] [Indexed: 01/01/2023]
Abstract
Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case-control study was performed to investigated the associations of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C>T and evaluated the association between the NQO1 609C>T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C>T and NQO2 -3423G>A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29-5.42 and OR = 1.88; 95 % CI = 1.02-3.49 respectively). Further, gene-gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C>T and NQO2 -3423G>A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C>T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98-14.19). Meta analysis of NQO 609C>T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C>T and NQO2 -3423G>A genetic variations modulate risk of EC in high-risk Kashmir population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow 226014, India
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Qureshi MA, Jan N, Dar NA, Hussain M, Andrabi KI. A novel p16INK4Amutation associated with esophageal squamous cell carcinoma in a high risk population. Biomarkers 2012; 17:552-6. [DOI: 10.3109/1354750x.2012.699556] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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SAMEER ASYED, ABDULLAH SAFIYA, NISSAR SANIYA, RASOOL ROOHI, SHAH ZAFFARA, AFROZE DIL, CHOWDRI NISSARA, SIDDIQI MUSHTAQA. The blues of P(16)INK(4a): aberrant promoter methylation and association with colorectal cancer in the Kashmir valley. Mol Med Rep 2012; 5:1053-1057. [PMID: 22218684 PMCID: PMC3493103 DOI: 10.3892/mmr.2012.740] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Accepted: 10/24/2011] [Indexed: 12/31/2022] Open
Abstract
Hypermethylation of the promoter region of the p16INK4a (p16) gene plays a significant role in the development and progression of colorectal cancer (CRC). The aim of the present study was to establish the role of the methylation status of the p16 gene in 114 CRC cases and to correlate it with the various clinicopathological parameters. Analysis of p16 promoter methylation was performed by methylation-specific PCR. Forty-eight (42.1%) of the CRC cases were found to be methylated for the p16 gene in our population. The methylation status was found to be associated with the gender, lymph node status, tumour stage, smoking status and tumour grade of the CRC patients. p16 plays a pivotal role in tumour development and progression to advanced stages.
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Affiliation(s)
- A. SYED SAMEER
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - SAFIYA ABDULLAH
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - SANIYA NISSAR
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - ROOHI RASOOL
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - ZAFFAR A. SHAH
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - DIL AFROZE
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - NISSAR A. CHOWDRI
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
| | - MUSHTAQ A. SIDDIQI
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir 190011, India
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Sameer AS, Nissar S, Qadri Q, Alam S, Baba SM, Siddiqi MA. Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri population. Hum Genomics 2011; 5:530-537. [PMID: 22155602 PMCID: PMC3525247 DOI: 10.1186/1479-7364-5-6-530] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2011] [Accepted: 01/31/2011] [Indexed: 12/20/2022] Open
Abstract
Cytochrome P450 2E1 (CYP2E1) is a key enzyme involved in the metabolic activation of procarcinogens such as N-nitrosoamines and low-molecular-weight organic compounds. The main aim of this study was to determine whether CYP450 2E1 polymorphisms are associated with the risk of colorectal cancer (CRC). We investigated the genotype distribution of the CYP2E1 gene RsaI and a 96-base pair (bp) insertion in 86 CRC cases in comparison with 160 healthy subjects. We found the frequency of the CYP2E1 RsaI genotype to be 53.5 per cent (46/86) for c1/c1, 17.4 per cent (15/86) for c1/c2 and 29.1 per cent (25/86) for c2/c2, and the CYP2E1 98-bp insertion frequencies to be 63.9 per cent (55/86) for non-insertion (i/i), 22.1 per cent (19/86) for heterozygous insertion (i/I) and 36.0 per cent (12/86) for homozygous insertion (I/I) among CRC cases. We also found the CYP2E1 RsaI c2/c2 and CYP2E1 98-bp heterozygous i/I genotypes to be significantly associated with an increased risk of CRC (p = 0.01). We suggest that CYP2E1 polymorphisms are involved in the susceptibility to developing CRC in the ethnic Kashmiri population.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
| | - Saniya Nissar
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
| | - Qurteeba Qadri
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
| | - Shafia Alam
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
| | - Shahid Mudasir Baba
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
| | - Mushtaq A Siddiqi
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India
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Sameer AS, Nissar S, Abdullah S, Chowdri NA, Siddiqi MA. DNA repair gene 8-oxoguanine DNA glycosylase Ser326Cys polymorphism and colorectal cancer risk in a Kashmiri population. DNA Cell Biol 2011; 31:541-6. [PMID: 21899442 DOI: 10.1089/dna.2011.1349] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
8-Oxoguanine DNA glycosylase (OGG1) is one of the important base excision repair enzymes that repair 8-oxoguanine lesion incorporated within the DNA of an individual by reactive oxygen species. The aim of this study was to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to colorectal cancer (CRC) in a Kashmiri population. We investigated the genotype distribution of the OGG1 gene in 114 CRC cases in comparison with 200 healthy subjects. There was no significant association between OGG1 Ser326Cys polymorphism and CRC, but the homozygous Cys/Cys variant genotype was associated with an increased risk of colon cancer (p<0.05). This study suggests that the OGG1 polymorphism is not associated with the risk of development of CRC in the Kashmiri population in general but modulates the risk of cancer development in colon via interaction with many dietary factors.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
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Malik MA, Zargar SA, Mittal B. A six-nucleotide deletion polymorphism in the casp8 promoter is associated with reduced risk of esophageal and gastric cancers in Kashmir valley. INDIAN JOURNAL OF HUMAN GENETICS 2011; 17:152-156. [PMID: 22345985 PMCID: PMC3276982 DOI: 10.4103/0971-6866.92090] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. To evaluate the role of CASP8 polymorphisms in esophageal (EC) and gastric cancers (GC) in the Kashmir valley, we examined the risk due to -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 in a case-control study. MATERIALS AND METHODS Genotypes of the CASP8 polymorphisms (-652 6N ins/del; rs3834129) were determined for 315 patients (135 EC and 108 GC) and 195 healthy controls by polymerase chain reaction. Data was statistically analyzed using Chi-square test and logistic regression model by using the SPSS software. RESULTS Carriers for the del allele of rs3834129 single nucleotide polymorphism were associated with decreased risk for both EC (odds ratio [OR] = 0.278; 95% confidence interval [95% CI] = 0.090-0.853; P = 0.025) and GC (OR = 0.397; 95% CI = 0.164-0.962; P = 0.041). Also, in a recessive model, our results showed that CASP8 -652 6N ins/del "del/del" allele was conferring significant low risk for both EC (OR = 0.380; 95% CI = 0.161-0.896; P = 0.027) and GC (OR = 0.293; 95% CI = 0.098-0.879; P = 0.029). However, interaction of CASP8 -652 6N ins/del genotypes with smoking and high consumption of salted tea did not further modulate the risk of EC and GC. CONCLUSIONS Polymorphism in CASP8 -652 6N ins/del polymorphism modulates the risk of EC and GC in Kashmir valley.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Showkat Ali Zargar
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
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Malik MA, Sharma KL, Zargar SA, Mittal B. Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi J Gastroenterol 2011; 17:301-306. [PMID: 21912055 PMCID: PMC3178916 DOI: 10.4103/1319-3767.84480] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 02/11/2011] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND/AIM Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers. PATIENTS AND METHODS To document the role of MMP-7 polymorphism in esophageal carcinogenesis, a case-control study was performed comprising 135 patients with esophageal cancer (EC) and 195 healthy controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were statistically analyzed using χ2 - test and logistic regression models. RESULTS Carriers for the MMP-7 (-181A>G) GG were associated with an increased risk for EC [odds ratio (OR = 2.17; 95% confidence interval (CI) = 1.21-3.92; P = 0.010; P-trend = 0.04]. Also, in a recessive model, our results showed that MMP-7 (-181A>G) GG allele conferred significantly higher risk for EC (OR =2.16; 95% CI = 1.31-3.54; P = 0.003). The high risk due to MMP-7 (-181GG) genotype was limited to squamous cell histology of EC (OR = 2.41; 95% CI = 1.27-4.56; P = 0.007). Although smoking (Hukka) and high consumption of salted tea are independent risk factors for EC, the interaction of MMP-7 (-181A>G) genotypes with these factors did not further modulate the risk of EC. CONCLUSIONS In conclusion, our results show that MMP-7 (-181A>G) GG carriers are at a higher risk of esophageal squamous cell carcinoma in Kashmir valley.
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Affiliation(s)
- Manzoor A. Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Kiran L. Sharma
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Showket A. Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
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Sameer AS, Shah ZA, Abdullah S, Chowdri NA, Siddiqi MA. Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population. Hum Genomics 2011; 5:441-452. [PMID: 21807601 PMCID: PMC3525962 DOI: 10.1186/1479-7364-5-5-441] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Accepted: 03/17/2011] [Indexed: 12/31/2022] Open
Abstract
The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05). Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of
Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences,
Soura, Srinagar, Kashmir, 190011, India
| | - Zaffar A Shah
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of
Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
| | - Safiya Abdullah
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of
Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
| | - Nissar A Chowdri
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences,
Soura, Srinagar, Kashmir, 190011, India
| | - Mushtaq A Siddiqi
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of
Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
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Sameer AS, Qadri Q, Siddiqi MA. GSTP1 I105V polymorphism and susceptibility to colorectal cancer in Kashmiri population. DNA Cell Biol 2011; 31:74-9. [PMID: 21711092 DOI: 10.1089/dna.2011.1297] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
The glutathione S-transferase (GST) enzyme encoded by the GSTP1 gene is one of the critical enzymes involved in detoxification of carcinogens. The substitution of isoleucine to valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity and hence less capability of effective detoxification. Hence, we investigated the role of GSTP1 I105V polymorphism in modulating the risk of colorectal cancer (CRC) associated in a Kashmiri population. We designed a case-control study in which 86 CRC cases were studied for GSTP1 I105V polymorphism against 160 controls taken from the general population employing the polymerase chain reaction-restriction length fragment polymorphism technique. There was no significant association between GSTP1 I105V genotypes and the disease, but the Val/Val genotype was associated with an increased risk with some clinicopathological parameters (odds ratio=1.5; 95% confidence interval=0.55-4.57). This study suggests that the GSTP1 I105V polymorphism may modulate CRC risk in the Kashmiri population.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India
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Sameer AS, Shah ZA, Nissar S, Mudassar S, Siddiqi MA. Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in the Kashmiri population. GENETICS AND MOLECULAR RESEARCH 2011; 10:1200-10. [PMID: 21732284 DOI: 10.4238/vol10-2gmr1067] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C→T and 1298 A→C, have been shown to impact various diseases, including cancer. The 677 C→T polymorphism has been widely investigated in different cancers and has been implicated as a risk factor for the development of various cancers. We investigated MTHFR C677T genotype frequency in colorectal cancer cases in the Kashmiri population and correlated this information with the known clinicopathological characters of colorectal cancer, in a case-control study. Eighty-six colorectal cancer cases were studied for MTHFR C677T polymorphism, compared to 160 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of MTHFR in our ethnic Kashmir population, i.e., CC, CT and TT, to be 68.6, 20.9 and 10.4% among colorectal cancer cases and 75.6, 16.9 and 7.5% among the general control population, respectively. There was a significant association between the MTHFR TT genotype and colorectal cancer in the higher age group. We conclude that the MTHFR C677T polymorphism slightly increases the risk for colorectal cancer development in our ethnic Kashmir population.
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Affiliation(s)
- A S Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Kashmir, India
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Malik MA, Zargar SA, Mittal B. Role of NQO1 609C>T and NQO2-3423G>A polymorphisms in susceptibility to gastric cancer in Kashmir valley. DNA Cell Biol 2011; 30:297-303. [PMID: 21294640 DOI: 10.1089/dna.2010.1115] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
NADPH: quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside: quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines. These enzymes also protect cells against oxidative damage from reactive oxygen species. The present study investigated the associations of genetic variants of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to gastric cancer (GC) as well as their interactions with known risk factors in Kashmir valley. A case control study was performed in 303 subjects (108 GC and 195 healthy controls). All subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed by chi-square test and logistic regression model. The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for GC, whereas NQO2 -3423G>A polymorphism did not show any association with GC. Also, NQO1 609C>T TT genotype showed significant association with gastric adenocarcinoma. The interaction of NQO1/NQO2 genotypes with high consumption of salted tea, a known risk factor, did not further modulate the risk of GC. In conclusion, NQO1 609C>T polymorphism shows association with GC risk in Kashmir valley.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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AL-QASEM ABEERJ, TOULIMAT MOHAMED, ELDALI ABDELMONEIMM, TULBAH ASMA, AL-YOUSEF NUJOUD, AL-DAIHAN SOOADK, AL-TASSAN NADA, AL-TWEIGERI TAHER, ABOUSSEKHRA ABDELILAH. TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution. Oncol Lett 2011; 2:363-369. [PMID: 22866089 PMCID: PMC3410563 DOI: 10.3892/ol.2011.236] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Accepted: 01/03/2011] [Indexed: 01/11/2023] Open
Abstract
Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals.
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Affiliation(s)
- ABEER J. AL-QASEM
- Department of Biological and Medical Research, King Saud University, Riyadh, Saudi Arabia
| | - MOHAMED TOULIMAT
- Department of Pathology, King Saud University, Riyadh, Saudi Arabia
| | - ABDELMONEIM M. ELDALI
- Department of Biostatistics, Epidemiology and Scientific Computing, King Saud University, Riyadh, Saudi Arabia
| | - ASMA TULBAH
- Department of Pathology, King Saud University, Riyadh, Saudi Arabia
| | - NUJOUD AL-YOUSEF
- Department of Biological and Medical Research, King Saud University, Riyadh, Saudi Arabia
| | | | - NADA AL-TASSAN
- Oncology Center, King Faisal Specialist Hospital and Research Center, King Saud University, Riyadh, Saudi Arabia
| | - TAHER AL-TWEIGERI
- Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia
| | - ABDELILAH ABOUSSEKHRA
- Department of Biological and Medical Research, King Saud University, Riyadh, Saudi Arabia
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Dikshit RP, Mathur G, Mhatre S, Yeole BB. Epidemiological review of gastric cancer in India. Indian J Med Paediatr Oncol 2011; 32:3-11. [PMID: 21731209 PMCID: PMC3124986 DOI: 10.4103/0971-5851.81883] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Stomach cancer is the one of the leading cause of cancer in southern region of India. Its incidence is decreasing worldwide yet on global scale stomach cancer remains one of the most common causes of cancer death. Etiology of gastric cancer includes Helicobacter pylori infection, diet and lifestyle, tobacco, alcohol and genetic susceptibility. In this review, we tried to find the contribution of Indian scientist in understanding the descriptive and observational epidemiology of stomach cancer. PubMed was used as a search platform using key words such as "stomach cancer, treatment, clinical characteristics, stomach cancer outcome, epidemiology, etiological factor and their corresponding Mesh terms were used in combination with Boolean operators OR, AND". Most of the reported studies on gastric cancer from India are case report or case series and few are case-control studies. Indian studies on this topic are limited and have observed H. pylori infection, salted tea, pickled food, rice intake, spicy food, soda (additive of food), tobacco and alcohol as risk factors for gastric cancer. More research is required to understand the etiology, develop suitable screening test, to demarcate high-risk population and to develop and evaluate the effect of primary prevention programs.
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Affiliation(s)
| | - Garima Mathur
- Department of Epidemiology, Tata Memorial Hospital, Mumbai, India
| | - Sharayu Mhatre
- Department of Epidemiology, Tata Memorial Hospital, Mumbai, India
| | - B. B. Yeole
- Population Based Cancer Registry, Indian Cancer Society, Mumbai, Maharashtra, India
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Sameer AS, Chowdri NA, Syeed N, Banday MZ, Shah ZA, Siddiqi MA. SMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene. BMC Cancer 2010; 10:300. [PMID: 20565773 PMCID: PMC2927996 DOI: 10.1186/1471-2407-10-300] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2009] [Accepted: 06/17/2010] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype. METHODS We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing. RESULTS The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05). CONCLUSION Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
| | - Nissar A Chowdri
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
| | - Nidda Syeed
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
| | - Mujeeb Z Banday
- Department of Biotechnology, Kashmir University, Hazratbal, Srinagar, Kashmir, India. 190006
| | - Zaffar A Shah
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
| | - Mushtaq A Siddiqi
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India. 190011
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Upadhyay R, Malik MA, Zargar SA, Mittal B. OGG1 Ser326Cys polymorphism and susceptibility to esophageal cancer in low and high at-risk populations of northern India. J Gastrointest Cancer 2010; 41:110-115. [PMID: 20069464 DOI: 10.1007/s12029-009-9124-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Esophageal cancer has diverse incidence worldwide, and genetic/environmental risk factors are supposed to be responsible for it. OGG1 Ser326Cys gene polymorphism (rs1052133) has been found to be associated with different cancer susceptibilities and interaction with different environmental factors. AIM OF THE STUDY The aim of this study is to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to esophageal cancer in two Northern Indian populations having different incidence rates. METHODS A total of 737 cases and controls from two high and low at-risk populations were selected for the study. All the subjects were genotyped by PCR with confronting two-pair primers. RESULTS No significant association was found between OGG1 Ser326Cys genotypes and esophageal cancer risk in both of the populations. Gene-environment analysis revealed no significant interaction between OGG1 Ser326Cys genotypes and smoking/high-salted tea intake habits. CONCLUSION OGG1 Ser326Cys polymorphism does not have a role in determining susceptibility to esophageal cancer either in high or in low at-risk populations of Northern India.
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Affiliation(s)
- Rohit Upadhyay
- Department of Genetics, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, 226014, India
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Sameer AS, Shah ZA, Syeed N, Banday MZ, Bashir SM, Bhat BA, Siddiqi MA. TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. GENETICS AND MOLECULAR RESEARCH 2010; 9:651-60. [PMID: 20449797 DOI: 10.4238/vol9-2gmr751] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.
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Affiliation(s)
- A S Sameer
- Department of Immunology and Molecular Medicine Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
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Malik MA, Upadhyay R, Mittal RD, Zargar SA, Mittal B. Association of xenobiotic metabolizing enzymes genetic polymorphisms with esophageal cancer in Kashmir Valley and influence of environmental factors. Nutr Cancer 2010; 62:734-742. [PMID: 20661821 DOI: 10.1080/01635581003605904] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1 genes with susceptibility to EC as well as their interaction with environmental factors such as smoking and high consumption of salted tea in Kashmir valley. All subjects were genotyped through polymerase chain reaction restriction fragment length polymorphism. Data was statistically analyzed using the chi-square test and logistic regression model. Results showed that GSTP1313 val/val and CYP2E1c1c2 genotypes imparted risk for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma [EADC; odds ratio (OR) = 3.24, 95% confidence interval (CI) = 1.30-8.05; OR = 4.20, 95% CI = 1.65-10.70], respectively. GSTM3AB genotype/B allele was found to be associated with low risk for EC. Tobacco smoking through hukka (water pipe) and consumption of salted tea itself were high risk factors for developing EC (OR = 21.44, 95% CI = 11.63-39.54; OR = 14.86, 95% CI = 8.41-26.24), and the risks were modulated through the interaction of GSTM3AB, GSTP1val/val genotypes. In conclusion, GSTP1val/val and CYP2E1c1c2 genotypes/c2 allele increased the risk of ESCC and EADC, respectively, in the Kashmiri population; whereas GSTM3AB genotype imparted lower risk for both ESCC and EADC.
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Affiliation(s)
- Manzoor Ahmad Malik
- Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
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Abstract
India, with a population of over a billion is likely to increase global concern on cancer, particularly that of head and neck. The increasing immigration of Indians is likely to influence other parts of the world and an analysis of cancer-related practices could serve as a model for defining cancer-prevention strategies across the globe. The objective of this study was to review the anti- and pro-carcinogenic practices in India pertaining to head and neck cancer. The published literature on practices, compounds/chemicals/crude reparations related to the head and neck cancer in India was retrieved for analysis, while unauthentic or local information was discarded. The anti-carcinogenic practices prevalent in India consisted of classically varied diet being predominantly vegetarian, along with spices, condiments, beverages etc. The pro-carcinogenic practices predominantly include all shades of alcoholism and tobacco intake. Moreover, the diverse culture of the country reflects unique regional practices. The enormous diversity in practices related to head and neck cancer in India is very unique and interesting. Cancer prevention strategies need to focus on these trends to define a better global prevention.
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Affiliation(s)
- A Mishra
- C.S.M. Medical University (King George Medical College), A-1/19, Sector H, Aliganj, Lucknow, UP, India.
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Malik MA, Upadhyay R, Modi DR, Zargar SA, Mittal B. Association of NAT2 gene polymorphisms with susceptibility to esophageal and gastric cancers in the Kashmir Valley. Arch Med Res 2009; 40:416-423. [PMID: 19766908 DOI: 10.1016/j.arcmed.2009.06.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2009] [Accepted: 06/17/2009] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS The high incidence of gastrointestinal cancers in the Kashmir Valley has been attributed to the presence of many chemical carcinogens such as nitrosamines and heterocyclic amines in tobacco and salted tea. Due to functional polymorphisms of the N-acetyltransferase 2 (NAT2) gene, there may be interindividual differences in the metabolism of heterocyclic amines. We undertook this study to determine the influence of NAT2 gene polymorphisms (rs1799929, rs1799930, rs1799931) as well as their interactions with environmental carcinogens on the modulation of risk of esophageal and gastric cancers (EC and GC) in the Kashmir Valley. METHODS A case/control study was performed involving 398 study subjects (182 controls, 123 EC and 93 GC). DNA samples were genotyped by PCR-RFLP method. RESULTS None of the three NAT2 polymorphic alleles was found to be independently associated with risk of EC/GC but haplotypes C(481)A(590)G(857) and T(481)A(590)G(857) significantly modulated the risk of EC and GC, respectively (OR=0.56; 95% CI=0.34-0.91; p=0.018 and OR=4.61; 95% CI=1.90-11.17; p=0.001). NAT2 slow acetylator genotypes (NAT2 *5, NAT2 *6, NAT2 *7) significantly increased the risk of esophageal squamous cell carcinoma (ESCC, OR=1.73; 95% CI=1.01-2.97; p=0.047). Smoking and salted tea consumption were independent risk factors, but they did not show any interaction with NAT2 slow acetylator genotypes. CONCLUSIONS NAT2 slow acetylator genotype may increase susceptibility to ESCC, and NAT2 haplotypes (C(481)A(590)G(857) and T(481)A(590)G(857)) may predict susceptibility to EC and GC in the Kashmir Valley.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Malik MA, Upadhyay R, Mittal RD, Zargar SA, Modi DR, Mittal B. Role of xenobiotic-metabolizing enzyme gene polymorphisms and interactions with environmental factors in susceptibility to gastric cancer in Kashmir Valley. J Gastrointest Cancer 2009; 40:26-32. [PMID: 19521675 DOI: 10.1007/s12029-009-9072-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2009] [Accepted: 05/27/2009] [Indexed: 01/27/2023]
Abstract
BACKGROUND Kashmir Valley has elevated incidence rate of gastric cancer (GC) and several environmental, host genetic factors have been suspected for it. Xenobiotic carcinogen exposure and interindividual differences in its cellular metabolism may modulate susceptibility to GC. AIM OF THE STUDY The aim of this study is to investigate the role of genetic variants of xenobiotic-metabolizing genes with susceptibility to GC in Kashmir Valley. METHODS A case-control study was performed in 303 subjects (108 GC and 195 healthy controls) to analyze the association of polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3, CYP1A1, and CYP2E1 genes in susceptibility to GC in Kashmir Valley. All subjects were genotyped through polymerase chain reaction-restriction fragment length polymorphism. RESULTS GSTM1null and CYP2E1c1c2 genotypes imparted risk for GC (odds ratio [OR] = 1.98, 95% confidence interval [95%CI] = 1.22-3.21, P = 0.006 and OR = 2.56, 95%CI = 1.25-5.25, P = 0.010, respectively). GSTM3AB genotype/B allele was found to be associated with low risk for GC. Smokers and high salted tea consumers themselves were at higher risk for GC (OR = 8.98, 95%CI = 5.16-15.62, P = 0.0001 and OR = 14.78, 95%CI = 8.02-27.23, P = 0.0001, respectively). Cancer risk was further enhanced in smokers with the GSTM1null genotype. CONCLUSION The results suggest that GSTM1null, GSTM3AB, and CYP2E1c1c2 genotypes modulate the risk of GC whereas GSTM1null genotypes enhance the risk of GC for smokers in the Kashmir population.
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Affiliation(s)
- Manzoor A Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, 226014, India
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Gupta PJ. Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. A prospective, randomized, placebo-controlled, double blind, crossover trial. ARQUIVOS DE GASTROENTEROLOGIA 2009; 45:124-7. [PMID: 18622465 DOI: 10.1590/s0004-28032008000200006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2007] [Accepted: 10/04/2007] [Indexed: 11/22/2022]
Abstract
BACKGROUND Red-hot chili pepper and other spices have been blamed for causing or exacerbating symptoms of anal pathologies like anal fissure and hemorrhoids. AIM To determine if consumption of chilies increases symptoms of acute anal fissures. METHODS Individual patients were randomized to receive capsules containing chili or placebo for one week in addition to analgesics and fiber supplement. Patients were asked to note score for symptoms like pain, anal burning, and pruritus during the study period. After 1 week, cross over treatment was administered to the same group of patients with the same methodology and results were noted at the end of 2 weeks. RESULTS Fifty subjects were recruited for this study. Forty three of them completed the trial (22 in the chili group and 21 in the placebo group). The daily mean pain score was significantly lower in the placebo group in the study period. Score 2.05 in chili group and 0.97 in placebo group. There was a significant burning sensation experienced by the patients in the chili group (score 1.85 for the chili group vs 0.71 for the placebo group). Patients mean recorded improvement score was significantly higher after taking placebo. Eighty one point three percent patients preferred placebo while 13.9% preferred chilies. Two patients had no preference. CONCLUSION Consumption of chili does increase the symptoms of acute anal fissure and reduces patient compliance.
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Affiliation(s)
- Pravin J Gupta
- Fine Morning Hospital and Research Center, Nagpur, India.
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Dar NA, Mir MM, Salam I, Malik MA, Gulzar GM, Yatoo GN, Ahmad A, Shah A. Association between copper excess, zinc deficiency, and TP53 mutations in esophageal squamous cell carcinoma from Kashmir Valley, India--a high risk area. Nutr Cancer 2009; 60:585-91. [PMID: 18791921 DOI: 10.1080/01635580802290231] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India--a high incidence area. The average level of copper was significantly higher (P < 0.0001) for patients than for controls, with a mean concentration of 169 microg/dl and 149 microg/dl for patients and controls, respectively. The control group consisted of 55 healthy individuals matched for age, sex, and place of residence of the patients. In contrast, the average level of zinc in patients was significantly lower than in controls (P < 0.0001), with a mean concentration of 86.8 microg/dl and 96.1 microg/dl for patients and controls, respectively. The levels of both copper and zinc showed significant differences based on gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P < 0.0001). To validate the general notion that imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.
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Affiliation(s)
- Nazir Ahmad Dar
- Department of Clinical Biochemistry, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India
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Gupta PJ. Effect of Red Chili Consumption on Postoperative Symptoms During the Posthemorrhoidectomy Period: Randomized, Double-blind, Controlled Study. World J Surg 2007; 31:1822-1826. [PMID: 17647055 DOI: 10.1007/s00268-007-9148-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The aim of this study was to determine whether there was any relation between consumption of chilies and postoperative symptoms after hemorrhoidectomy in patients with grade III or IV hemorrhoidal disease. A total of 60 patients were randomly assigned to receive antibiotics and analgesics alone (control patients) or daily consumption of 3 g of chili powder along with identical antibiotics and analgesics (chili group). The evaluation of symptoms-pain, anal burning, pruritus, bleeding-during the postoperative period was assessed by means of patients' self-questionnaires. A global score for evaluating each postoperative symptom was compared between the two groups at the 1-week follow-up. No significant difference in age, sex distribution, or grade of disease was noted between the two groups at baseline. The incidence of post-hemorrhoidectomy symptoms was higher in the group consuming chilies during the first postoperative week. The global score for postoperative pain (14.60 for the chili group vs. 7.97 for the control group, p < 0.001) and for anal burning (12.90 for the chili group vs. 7.82 for the control group, p < 0.0001) were significant. Although bleeding (6.95 in the control group and 7.57 in the chili group, p < 0.81) and pruritus (8.06 in the control group and 8.75 in the chili group, p < 0.69) were more common in the chili group, the difference did not achieve statistical significance. This study shows that consumption of 3 g of red chilies per day during the postoperative period after hemorrhoidectomy increases the intensity of typical postoperative symptoms, stool frequency, and the consumption of analgesics.
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Eachkoti R, Hussain I, Afroze D, Aejazaziz S, Jan M, Shah ZA, Das BC, Siddiqi MA. BRCA1 and TP53 mutation spectrum of breast carcinoma in an ethnic population of Kashmir, an emerging high-risk area. Cancer Lett 2006; 248:308-20. [PMID: 16996204 DOI: 10.1016/j.canlet.2006.08.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2006] [Revised: 06/05/2006] [Accepted: 08/08/2006] [Indexed: 12/18/2022]
Abstract
Breast cancer shows geographical variation in its incidence, even within areas of ethnic homogeneity. Kashmir valley (India), over past few years, witnesses an increase in incidence and occurrence of familial, early onset, and male breast cancer in its unexplored ethnic population. Here, we make a preliminary attempt to estimate the nature and frequency of BRCA1 and TP53 gene mutations of breast cancer patients from Kashmir. PCR-SSCP analysis followed by direct sequencing revealed the presence of only two germline intronic variations (c.199+67T>C and c.5396+187T>C) in BRCA1 gene in only 5.26% (2/38) patients while as 44% (11/25) of sporadic breast cancer patients harboured significant amount of somatic mutations in TP53 (p=0.0074; OR=0.053). The 17 mutations found in TP53 in 11 patients, comprised of 13 substitutions [11 single-base (9 transitions+2 transversions), 1 double-base and 1 complex] and four insertions. The 11 substitutions represent missense mutations, leading to aminoacid substitution while as rest two were silent mutations. The four insertions represented three frame-shifts and one non-sense mutation. The mutation effect data was found to be significant (p=0.0002). Significant amount of mutations were found in exon 6 (p=0.04; OR=0.273) and a combination of exons 6 and 7 (p=0.0145; OR=14.22) of TP53. Comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Kashmiri women that need further investigations. The infrequent presence of germline BRCA1 mutations in our study agree with the idea that a great proportion of moderate risk breast cancer population could be due to the susceptibility genes distinct from BRCA1. However, high frequency of somatic TP53 gene mutations implicates TP53 as a predominant factor for breast carcinogenesis in moderate risk ethnic Kashmiri population. The study also suggests TP53 as a potential molecular marker and prognostic tool, at least in a subset of sporadic breast tumors.
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Affiliation(s)
- Rafiqa Eachkoti
- Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India
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Murtaza I, Mushtaq D, Margoob MA, Dutt A, Wani NA, Ahmad I, Bhat ML. A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley. World J Gastroenterol 2006; 12:4033-4037. [PMID: 16810754 PMCID: PMC4087716 DOI: 10.3748/wjg.v12.i25.4033] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2006] [Revised: 02/14/2006] [Accepted: 02/18/2006] [Indexed: 02/07/2023] Open
Abstract
AIM To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India. METHODS All cases (n = 51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient's age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls. RESULTS Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P<0.05) with familial history of cancer (CD = 58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable "Hakh" (CD = 19.5), red chillies (CD = 20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD = 1.1). CONCLUSION Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and "Hakh", that are rich in nitrosoamines and familial cancer history.
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Affiliation(s)
- Imtiyaz Murtaza
- Division of PHT, SKUAST (K), Shalimar Campus, Srinagar, Kashmir, 191121 (J and K), India.
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Guadagnin SG, Rath S, Reyes FGR. Evaluation of the nitrate content in leaf vegetables produced through different agricultural systems. FOOD ADDITIVES AND CONTAMINANTS 2005; 22:1203-8. [PMID: 16356883 DOI: 10.1080/02652030500239649] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The nitrate content of leafy vegetables (watercress, lettuce and arugula) produced by different agricultural systems (conventional, organic and hydroponic) was determined. The daily nitrate intake from the consumption of these crop species by the average Brazilian consumer was also estimated. Sampling was carried out between June 2001 to February 2003 in Campinas, São Paulo State, Brazil. Nitrate was extracted from the samples using the procedure recommended by the AOAC. Flow injection analysis with spectrophotometric detection at 460 nm was used for nitrate determination through the ternary complex FeSCNNO+. For lettuce and arugula, the average nitrate content varied (p < 0.05) between the three agricultural systems with the nitrate level in the crops produced by the organic system being lower than in the conventional system that, in turn, was lower than in the hydroponic system. For watercress, no difference (p < 0.05) was found between the organic and hydroponic samples, both having higher nitrate contents (p < 0.05) than conventionally cultivated samples. The nitrate content for each crop species varied among producers, between different parts of the plant and in relation to the season. The estimated daily nitrate intake, calculated from the consumption of the crops produced by the hydroponic system, represented 29% of the acceptable daily intake established for this ion.
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Affiliation(s)
- S G Guadagnin
- Faculty of Food Engineering, Department of Food Science, State University of Campinas, PO Box 6121, 13084-971 Campinas, SP, Brazil
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Mir MM, Dar NA, Gochhait S, Zargar SA, Ahangar AG, Bamezai RNK. p53 mutation profile of squamous cell carcinomas of the esophagus in Kashmir (India): a high-incidence area. Int J Cancer 2005; 116:62-8. [PMID: 15761872 DOI: 10.1002/ijc.21002] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. Kashmir valley, in north of India, has been described as a high-risk area for ESCC. Here, we make a preliminary attempt to study mutations in exons 5-8 (the DNA binding domain) of the tumor suppressor gene, p53, in 55 ESCC patients from Kashmir. Polymerase chain reaction followed by direct sequencing analysis revealed the presence of mutations in 36.36% (20/55) tumors, assessed for the extent of allelic instability. The 20 mutations, found in 20 patients, comprised of 17 single-base substitutions (11 transitions + 6 transversions) and 3 deletions. The 17 single-base variations represented 12 missense mutations, 2 nonsense mutations and 3 variations located in intron 6, 1 of which resulted in a splicing variant. The patients when compared for the incidence of p53 mutation with various demographic features revealed females to be at increased risk (p = 0.016; OR = 4.13; 95% CI = 1.26-13.46). Comparison of mutation profile with other high-risk areas reflected both differences and similarities indicating coexposure to a unique set of risk factors. This might be due to the special dietary and cultural practices of Kashmir that needs validation, as does the gender-based difference in the incidence of p53 mutation observed in this study.
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Affiliation(s)
- Mohammad Muzaffar Mir
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
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