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Miao LF, Wang XY, Ye XH, Cui MS, He XF. Combined effects of GSTM1 and GSTT1 polymorphisms on breast cancer risk: A MOOSE-compliant meta-analysis and false-positive report probabilities test. Medicine (Baltimore) 2019; 98:e14333. [PMID: 30732156 PMCID: PMC6380837 DOI: 10.1097/md.0000000000014333] [Citation(s) in RCA: 3] [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] [Indexed: 12/16/2022] Open
Abstract
Many molecular epidemiology studies have reported an association between the combined effects of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms on breast cancer risk. However, the results have been controversial.A meta-analysis was performed to clarify this issue.Meta-analysis of observational studies in epidemiology guidelines was used. Pooled the crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model or fixed-effects model. Several subgroup analyses were conducted by ethnicity, source of control, matching, and menopausal status. In addition, we also performed sensitivity analysis and publication bias. Moreover, a false-positive report probability (FPRP) test was applied to assess positive results.A significantly increased breast cancer risk was observed in overall population (GSTM1 null/GSTT1 present [- +] vs GSTM1 present/GSTT1 present [+ +]: OR = 1.19, 95% CI: 1.03-1.36, GSTM1 null/GSTT1 null [- -] vs + +: OR = 1.63, 95% CI: 1.29-2.06, (- +) + GSTM1 present/GSTT1 null (+ -) vs + +: OR = 1.17, 95% CI: 1.05-1.31, (- +) + (+ -) + (- -) vs + +: OR = 1.27, 95% CI: 1.12-1.44, and - - vs (- +) + (+ -) + (+ +): OR = 1.39, 95% CI: 1.17-1.66) and several subgroup analyses, such as Caucasians, Indians, postmenopausal women, and so on. However, positive results were only considered noteworthy in overall population (- - vs + +: FPRP = 0.150 and (- +) + (+ -) + (- -) vs + +: FPRP = 0.162). Moreover, no significant association was observed when we used the trim and fill method to adjust the pooled data from all populations. Further, none of positive results of sensitivity analysis were considered noteworthy (FPRP >0.2).These positive findings should be interpreted with caution and indicate that an increased breast cancer risk may most likely result from false-positive results, rather than from true associations or biological factors on the combined effects of GSTM1 and GSTT1. Future studies should be based on sample sizes well-powered and attention needs to be paid to study design to further identify this issue.
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Affiliation(s)
- Li-Feng Miao
- Department of Galactophore, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi
| | - Xiao-Yan Wang
- Department of Epidemiology and Health Statistics, Basic Medical College of Zhejiang University of Traditional Chinese Medicine
| | - Xiang-Hua Ye
- Department of Radiotherapy, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
| | - Meng-Shen Cui
- Department of Galactophore, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi
| | - Xiao-Feng He
- Department of Science and Education, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi, PR China
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The Value of Pepsinogen in GC Screening: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:7087232. [PMID: 30804996 PMCID: PMC6360615 DOI: 10.1155/2019/7087232] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 08/22/2018] [Accepted: 10/20/2018] [Indexed: 12/20/2022] Open
Abstract
Background The current gold standard for gastric cancer (GC) screening is pathology or a barium meal followed by X-ray. This is not applicable to a wide range of screening capabilities due to the lack of operability. This article used a meta-analysis to evaluate the value of pepsinogen (PG) screening for GC. Methods PubMed, EMbase, the Cochrane Library, CNKI, WanFang, VIP, and CBM databases were systematically searched for published studies that used serum PG to diagnose GC. Articles were searched from January 2003 to January 2018. Two reviewers independently screened the literature according to specified inclusion and exclusion criteria. The data were extracted and evaluated, and the quality of the methodologies evaluated using the QUADAS entry. The meta-analysis (MA) was performed using Meta-DiSc 1.4 software. Stata 12.0 software was used to assess publication bias. Results A total of 19 studies were finally included from a total of 169,009 cases. The MA showed a combined sensitivity and specificity of 0.56 (95% CI (0.53-0.59), P < 0.01) and 0.71 (95% CI (0.70-0.71), P < 0.01), respectively. The combined likelihood ratios were +LR = 2.82 (95% CI (2.06-3.86), P < 0.01) and -LR = 0.56 (95% CI (0.45-0.68), P < 0.01). The combined DOR was 5.41 (95% CI (3.64~ 8.06), P < 0.01), and the area under the SROC curve was 0.7468. Conclusions Serum PG provides medium levels of sensitivity and specificity for GC assessment. To be used in a clinical setting, further high-quality research must be performed and verified.
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miR-34a and miR-125b Expression in HPV Infection and Cervical Cancer Development. BIOMED RESEARCH INTERNATIONAL 2015; 2015:304584. [PMID: 26180794 PMCID: PMC4477216 DOI: 10.1155/2015/304584] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Accepted: 12/02/2014] [Indexed: 12/15/2022]
Abstract
We aimed to characterize miR-125b and miR-34a expression in 114 women with different cervical lesions: normal epithelium with (n = 20) and without (n = 29) HPV infection; LSIL (n = 28); HSIL (n = 29); and ICC (n = 8). miRNA expression analysis was performed by comparing the distinct groups with the reference group (women with normal epithelium without HPV). For miR-125b, we observed a twofold (2−ΔΔCt = 2.11; P = 0.038) increased expression among women with normal epithelium with HPV infection and a trend of downregulation in different cervical lesions including an 80% reduction (2−ΔΔCt = 0.21; P = 0.004) in ICC. Similarly, miR-34a expression analysis revealed an increased expression (2−ΔΔCt = 1.69; P = 0.049) among women with normal cervix and HPV infection, and despite no significant correlation with cervical lesions, its expression was increased by twofold (2−ΔΔCt = 2.08; P = 0.042) in ICC. Moreover, miR-125b levels were able to predict invasive cancers with 88% sensitivity and 69% specificity. Results showed that while miR-34a expression seems to be correlated with invasive cervical cancer, miR-125b expression is significantly changed within the different cervical lesions and their levels should be further investigated as possible predictive/prognostic biomarkers using a noninvasive approach.
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Kikuste I, Marques-Pereira R, Monteiro-Soares M, Pimentel-Nunes P, Areia M, Leja M, Dinis-Ribeiro M. Systematic review of the diagnosis of gastric premalignant conditions and neoplasia with high-resolution endoscopic technologies. Scand J Gastroenterol 2013; 48:1108-17. [PMID: 24047392 DOI: 10.3109/00365521.2013.825315] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
AIM. The aim of the article is to systematically review the current evidence on the diagnostic use of narrow band imaging (NBI), flexible spectral imaging color enhancement (FICE) and endoscopic image enhancement technology i-scan endoscopies for gastric precancerous and cancerous lesions. MATERIALS AND METHODS. Original manuscripts were searched in PubMed until October 2012. Pertinent data were collected and pooled diagnostic accuracy measures were estimated when possible. RESULTs. In total, 38 studies were evaluated. Thirty-one studies were included for NBI and 7 studies for FICE assessment in this systematic review. No article was found meeting inclusion criteria for i-scan endoscopy. The most defined and evaluated outcomes were cancer-related (n = 26). Quality Assessment of Diagnostic Accuracy Studies score varied from 9 to 12 (out of 14). Only few studies assessed the interobserver reliability. On a patient level analysis, NBI's pooled sensitivity, specificity and diagnostic odds ratio were 0.67 (95% CI: 0.61-0.73), 0.81 (95% CI: 0.76-0.85) and 22.71 (95% CI: 12.53-41.1), respectively for diagnosing normal mucosa; 0.86 (95% CI: 0.82-0.90), 0.77 (95% CI: 0.73-0.80) and 17.01 (95% CI: 1.4-207.2) for intestinal metaplasia and 0.90 (95% CI: 0.84-0.94), 0.83 (95% CI: 0.80-0.86) and 47.61 (95% CI: 4.61-491.34) for dysplasia. Owing to the insufficient data and different definitions, we could not aggregate the results for FICE. CONCLUSION. Gastric pattern descriptions have been proposed for NBI and FICE studies by gathering all descriptions in one single description. The classification systems varied between studies, a single description of gastric mucosal features with HR--scopes or at least per technology--will have to be agreed on.
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Affiliation(s)
- Ilze Kikuste
- CINTESIS, Porto Faculty of Medicine , Porto , Portugal
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Freire P, Figueiredo P, Cardoso R, Donato MM, Sá A, Portela F, Romãozinho JM, Sofia C. Card15 mutations and gastric cancer in a Portuguese population. Scand J Gastroenterol 2013; 48:1188-97. [PMID: 24047397 DOI: 10.3109/00365521.2013.832370] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND. CARD15 is involved in the innate immune response and mutations of this gene have been linked with increased risk of Crohn's disease and colorectal cancer. The relation between CARD15 mutations and gastric cancer (GC) remains controversial. AIMS. To assess whether CARD15 mutations are risk factors for GC in Portugal and whether there are genotype-phenotype correlations in these patients. METHODS. The 3 main CARD15 mutations (3020insC, R702W and G908R) were searched in 150 patients with GC and in 202 healthy controls. RESULTS. Overall, CARD15 mutations were found in 28 patients (18.7%) and in 27 controls (13.4%) (p = 0.176). Individually, the incidence of 3020insC was significantly higher in patients than in controls (6.0% vs. 1.0%, p = 0.021). This polymorphism was linked with an increased risk for the intestinal-type of GC (p = 0.002), while no association was found with the diffuse and/or mixed types. Genotype frequencies for R702W (10.0% vs. 7.9%) and G908R (4.0% vs. 4.0%) were not statistically different between the two groups. Similarly, no significant associations were detected between these two polymorphisms and the different histological GC types. No correlations were observed between CARD15 mutations and family history, mean age at diagnosis or GC stage. CONCLUSIONS. The CARD15 3020insC variant is a risk factor for intestinal GC in Portugal. CARD15 variants are not correlated with age of diagnosis or family aggregation of the disease neither with the GC stage.
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Affiliation(s)
- Paulo Freire
- Department of Gastroenterology, Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
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Haidari M, Nikbakht MR, Pasdar Y, Najaf F. Trend analysis of gastric cancer incidence in Iran and its six geographical areas during 2000-2005. Asian Pac J Cancer Prev 2013; 13:3335-41. [PMID: 22994757 DOI: 10.7314/apjcp.2012.13.7.3335] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE Gastric cancer is the fourth most common cancer worldwide. While it is one of the most common cancers in Iran, there are only limited data regarding incidence trends in the country. This study is the first of its type to investigate trends across six geographical areas during 2000-2005 using cancer registry data. MATERIALS AND METHODS The registered data for gastric cancer cases in National Cancer Registry System were extracted from the Ministry of Health and Medical Education, Center for Disease Control and Management, code C16. First, according to WHO population, the sex-standardized incidence rate in both sexes and then the trends of incidence rate during 2000-2005 were investigated separately for different geographical areas of the country. RESULTS The incidence rates of gastric cancer in Iran and its six geographical areas during 2000-2005 were increasing albeit with differences in their slopes. The overall incidence rate increased from 2.8 in 2000 to 9.1 per 100,000 persons per year in 2005, rising from 4.1 to 13.2 in men. The average six-year incidence of gastric cancer in the central and northwestern border of Caspian Sea was 7.8 per 100,000 persons per year, while it was 0.9 per 100,000 persons per year in the border of the Persian Gulf. Generally the incidence rate in men was higher than in women. CONCLUSION Iran is one of the high-risk areas for gastric cancer. Increase in incidence might continue in the future partly because of improvement in cancer registry systems as well as increase in risk of this cancer.
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Genetic polymorphims of estrogen receptor alpha -397 PvuII (T>C) and -351 XbaI (A>G) in a portuguese population: prevalence and relation with breast cancer susceptibility. Mol Biol Rep 2013; 40:5093-103. [PMID: 23666105 DOI: 10.1007/s11033-013-2611-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Accepted: 04/30/2013] [Indexed: 10/26/2022]
Abstract
Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between -397 PvuII (T>C) and -351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case-control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR-RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95% CI 0.070-0.456; P<0.001) or heterozigozity (OR 0.223; 95% CI 0.089-0.561; P=0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95% CI 0.049-1.035; P=0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95% CI 0.194-0.843; P=0.014), compared with PX (PPXX+PPXx+PpXX+PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D=0.044, r2=0.049, X2=5.216, P=0.022) and controls (D=0.090, r2=0.139, X2=16.819, P<0.001), but not in the entire sample population analyzed as a whole (D=0.087, r2=0.0076, X2=1.733, P=0.188). In conclusion, in this case-control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.
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Faria GR, Pinto-de-Sousa J, Preto JR, Sousa HS, Barbosa JA, Costa-Maia J. Three decades of clinical-pathological trends in gastric cancer: prospective data from a Portuguese hospital. Int J Surg 2013; 11:472-6. [PMID: 23602895 DOI: 10.1016/j.ijsu.2013.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Accepted: 04/10/2013] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Gastric cancer is a heterogeneous disease, whose pathological and clinical patterns have changed in the last decades. In most western countries, decreases in incidence and mortality and a proximal migration have been reported. The clinical and pathological trends in an European country with high prevalence of gastric cancer were reviewed, based on the patients treated at a University Hospital. METHODS Analysis of a prospective database with 1618 patients who underwent surgery for gastric cancer in the last 3 decades. The patients were divided in 3 groups according to decades and the cohorts were analyzed according to demographic, surgical and pathological factors. RESULTS The mean age increased from 59.8 to 65.6 years. Antral tumors and intestinal cancer were the most frequent. The rate of complete resection increased as well as the percentage of total gastrectomies and D2-type lymphadenectomies. There was an increase both in early stage carcinomas and in surgically treated Stage-IV carcinomas. The median overall crude survival almost doubled from 14 to 22 months (p = 0.003), but once stratified for stage, only in stage II patients could we observe a significant increase in survival time. (29-47 months; p = 0.047). CONCLUSION The proximal migration described for Western Europe was not observed and the intestinal-type carcinoma is still the most frequent. We are treating older patients, often with more advanced disease. In spite of an increasing surgical aggressiveness, the prognosis has only been significantly improved in Stage-II cancers. The prognosis for advanced cancer is still dismal, hence the need for effective adjuvant treatments.
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Affiliation(s)
- Gil R Faria
- São João Medical Center/Faculty of Medicine, University of Porto, Surgery Department, Portugal.
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Heat shock protein 27 expression is inversely correlated with atrophic gastritis and intraepithelial neoplasia. Dig Dis Sci 2013; 58:381-8. [PMID: 22886594 DOI: 10.1007/s10620-012-2342-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Accepted: 07/25/2012] [Indexed: 01/04/2023]
Abstract
BACKGROUND Intestinal-type gastric carcinomas progress through several sequential steps, including atrophic gastritis, intestinal metaplasia, dysplasia, and cancer. AIM We investigated heat shock protein 27 (HSP27) expression in gastric neoplasia and background gastric mucosa to assess its involvement in gastric carcinogenesis. METHODS We used real-time quantitative polymerase chain reaction to examine HSP27 expression in gastric neoplasias and background gastric mucosae of 30 patients with intraepithelial neoplasias and in gastric mucosae of 30 patients without gastric neoplasia. Immunohistochemical staining was performed on 30 advanced gastric cancer tissues. RESULTS HSP27 expression was negatively associated with atrophic gastritis. HSP27 expression in the background gastric mucosa of neoplasia-bearing patients was significantly lower than in the mucosa of those without gastric neoplasia. In tumor necrosis factor α-treated gastric cancer cells, HSP27 knockdown increased cell death and accumulation of the reactive oxygen species that link inflammation to cancer. Poorly differentiated tumors most frequently had high HSP27 levels. Dedifferentiation of cancer cells is associated with an epithelial-mesenchymal transition (EMT) signaling pathway. In gastric cancer MKN-1 cells, HSP27 knockdown upregulated E-cadherin and downregulated vimentin and smooth muscle actin, but this did not occur in MKN-74 cells. CONCLUSION HSP27 expression in gastric mucosae is inversely correlated with intraepithelial neoplasia, a probable precursor to gastric cancer, and HSP27 expression in cancer is positively correlated with poor differentiation.
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Lacerda GF, Pinheiro PS, Cabral JM, Câmara JG, Rodrigues VL. Cancer in the Azores: initial results from a recently established population-based cancer registry. REVISTA BRASILEIRA DE EPIDEMIOLOGIA 2012; 15:285-97. [DOI: 10.1590/s1415-790x2012000200006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2011] [Accepted: 02/16/2012] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION: The Azores archipelago has long been the Portuguese region that presents the highest mortality rates for certain cancers. Lack of incidence data has prevented the evaluation of the actual burden of this disease in the Azorean population. METHODS: Malignant tumours (ICD-O 5th Digit /3) initially diagnosed between the January 1st 2000 and December 31st 2002 were retrieved from the database of the recently established population-based cancer registry. Crude, age-specific and age-standardized rates were calculated and confidence intervals were estimated using Poisson approximation. Relative risks of developing cancer in the Azores when compared to mainland Portugal have been represented by standardized ratios. Quality indicators, including Mortality:Incidence (M:I) ratios, were also assessed. RESULTS: Overall, the data shows a high incidence rate for some malignant diseases, specifically in men. Compared to those living in mainland Portugal, both Azorean men (RR 1.412; 99% CI 1.407-1.416) and women (1.127; 1.125-1.129) presented a significantly higher risk of developing cancer, all sites combined. When compared with other cancer registries, a less favourable cancer survival pattern is reported in the Azores, as emphasized by higher M:I ratios for several cancer sites. CONCLUSIONS: A preliminary analysis of the results suggests the presence of some major risk factors in the Azorean population, namely tobacco smoking in men. Higher M:I ratios would also point to survival disparities between the Azores archipelago and the continent, which should be further studied.
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Epidermal Growth Factor Genetic Variation Associated With Advanced Cervical Cancer in Younger Women. Am J Clin Oncol 2012; 35:247-50. [DOI: 10.1097/coc.0b013e31820dbbf5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Ramalhinho ACM, Fonseca-Moutinho JA, Breitenfeld Granadeiro LATG. Positive association of polymorphisms in estrogen biosynthesis gene, CYP19A1, and metabolism, GST, in breast cancer susceptibility. DNA Cell Biol 2012; 31:1100-6. [PMID: 22300440 DOI: 10.1089/dna.2011.1538] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE This case-control study was conducted in order to evaluate the potential role of polymorphic genes encoding enzymes involved in estrogen biosynthesis (CYP19A1) and metabolism (GSTM1, GSTT1, and GSTP1), and their action in modulating individual susceptibility to breast cancer. METHODS Genomic DNA was extracted from blood samples of 101 patients with histological diagnosis of breast cancer and 121 healthy women. Genotyping analyses of CYP19A1 codon 39 Trp/Arg (T/C), GSTM1 and GSTT1 homozygous deletions, and GSTP1 codon 105 Ile/Val (A/G) were performed by polymerase chain reaction-based methods. RESULTS Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. Significant statistical association of the TC/CC genotypes combined with breast cancer risk was found, with reference to TT genotype (OR=1.770; 95% CI=1.036-3.024; p=0.036). Also, CYP19A1 arginine allele in homozygosity or heterozygosity (TC/CC) was associated with a significant increased risk for breast cancer when associated to GSTM1 null genotype (OR=6.158; 95% CI=2.676-14.171; p<0.001) and GSTT1 null genotype (OR=4.870; 95% CI=2.216-10.700; p<0.001). The three-way combination of CYP19A1 TC/CC, GSTM1 null, and GSTT1 null polymorphism was related with significant increased risk for breast cancer (OR=11.429; 95% CI=3.590-36.385; p<0.001). Valine alleles compared with isoleucine alleles in codon 105 in GSTP1, in combination with CYP19A1 genotypes, were not associated with an increase of breast cancer development. CONCLUSIONS Our results suggest that the effect of CYP19A1 T/C polymorphism in susceptibility to breast cancer development can be modulated by the presence of GSTM1 and GSTT1, but not GSTP1.
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Silva J, Ribeiro J, Sousa H, Cerqueira F, Teixeira AL, Baldaque I, Osório T, Medeiros R. Oncogenic HPV Types Infection in Adolescents and University Women from North Portugal: From Self-Sampling to Cancer Prevention. JOURNAL OF ONCOLOGY 2011; 2011:953469. [PMID: 22174713 PMCID: PMC3228361 DOI: 10.1155/2011/953469] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 10/13/2011] [Indexed: 01/07/2023]
Abstract
This study aimed to characterize the HPV infection status in adolescents and young university women in Portugal. The distribution of HPV genotypes was evaluated by PCR DNA genotyping after self-sampling collection from 435 women of exfoliated cervical cells using a commercial kit. We observed an overall frequency of HPV infection of 11.5%. Furthermore, HPV DNA prevalence was 16.6% in those young women that self-declared as sexually active. The more frequently detected HPV types were 31, 16, 53, and 61. Statistical analysis identified median age (OR = 3.56; P = 0.001), the number of lifetime sexual partners (OR = 4.50; P < 0.001), and years of sexual activity (OR = 2.36; P = 0.008) as risk factors for HPV acquisition. Hence, our study revealed that oncogenic HPV infection is common in young asymptomatic women Portuguese women, with a history of 2-5 sexual partners and over 2 year of sexual activity. Moreover, these results demonstrate that HPV detection performed in self-collected samples may be important to appraise better preventive strategies and to monitorize the influence of vaccination programmes within different populations.
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Affiliation(s)
- Jani Silva
- Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
| | - Joana Ribeiro
- Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Hugo Sousa
- Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Molecular Virology Laboratory of Virology Service, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4099-003 Porto, Portugal
| | - Fátima Cerqueira
- CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- CEQUIMED, Faculty of Pharmacy, University of Porto, 4050-047 Porto, Portugal
| | - Ana Luisa Teixeira
- Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Molecular Virology Laboratory of Virology Service, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4099-003 Porto, Portugal
| | - Ines Baldaque
- Molecular Virology Laboratory of Virology Service, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Teresa Osório
- LPCC, Liga Portuguesa Contra O Cancro, Nucleo Regional do Norte, 4200-177 Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- Molecular Virology Laboratory of Virology Service, Portuguese Institute of Oncology of Porto, Road Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4099-003 Porto, Portugal
- LPCC, Liga Portuguesa Contra O Cancro, Nucleo Regional do Norte, 4200-177 Porto, Portugal
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Syrjänen K, Di Bonito L, Gonçalves L, Murjal L, Santamaria M, Mahovlic V, Karakitsos P, Onal B, Schmitt FC. Cervical cancer screening in Mediterranean countries: implications for the future. Cytopathology 2010; 21:359-67. [PMID: 20718841 DOI: 10.1111/j.1365-2303.2010.00795.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Prompted by feedback from the 34th European Congress of Cytology (ECC), the practice of including a special symposium in the programme was continued in the 35th ECC in Lisbon (2009) by arranging a satellite symposium entitled 'Cervical Cancer Screening in the Mediterranean Countries'. Because of the importance to the future of this discipline, it was felt appropriate to summarize the highlights of this symposium here. Cervical cancer prevention strategies in the countries participating in the symposium (Portugal, Spain, Italy, Croatia, Greece and Turkey) appear to be highly variable. As yet, none of these countries can demonstrate a fully implemented national screening programme, but all are in different phases of designing and/or setting up such a programme, which is important. At present, the time-honoured concept of cervical cancer prevention by Pap smear screening is under review, because prophylactic human papillomavirus (HPV) vaccines demonstrate a potential to prevent the vast majority (albeit not all) of cases of cervical cancer in the foreseeable future. Cervical cancer screening is still needed in this emerging era of HPV vaccination, but clearly the existing screening strategies must be modified to provide a cost-effective combination of vaccination and screening. If the currently evaluated new screening strategies, such as HPV testing followed by cytology triage, become a reality, there is the likelihood that the Pap test will have only a secondary role, subordinate to HPV testing. Supporters of this scenario claim that Pap test performance will deteriorate in vaccinated populations. Reduced positive predictive value (PPV), due to lower disease prevalence, is inevitable, however, and this would also affect HPV tests. Any decline in sensitivity and specificity depends on human performance, and as such is avoidable by taking appropriate preventive measures. As clinical cytologists, we should focus attention on minimizing the risk to the Pap test of falling sensitivity because of unfamiliarity with abnormal cells, and also of reduced specificity if the fear of missing significant disease leads to overcalling of benign abnormalities.
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Affiliation(s)
- K Syrjänen
- Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
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Sun J, Ouyang X, Yoshioka H, Wang W, Fan C, Li H, Wang J, Liu Y, Su L, Ma H, liu Y, Zhang Y, Zhang X, Wang X, Hu Y. A progressive rise in stomach cancer-related mortality rate during 1970–1995 in Japanese individuals over 85 years of age. J Appl Stat 2009. [DOI: 10.1080/02664760802582272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Dinis-Ribeiro M, Pimentel-Nunes P, Afonso M, Costa N, Lopes C, Moreira-Dias L. A European case series of endoscopic submucosal dissection for gastric superficial lesions. Gastrointest Endosc 2009; 69:350-5. [PMID: 19185696 DOI: 10.1016/j.gie.2008.08.035] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2008] [Accepted: 08/26/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND EMR is an accepted method for resection of superficial lesions in the GI tract. However, because it leads, not unusually, to piecemeal resection, histopathologic interpretation problems and an increased risk of recurrence are noticeable. Endoscopic submucosal dissection (ESD) allows a higher rate of en bloc resection, with low recurrence. Nevertheless, this technique, namely in the upper-GI tract, has rarely been described in Western countries, probably because of the rarity of gastric cancer in most countries. OBJECTIVE To describe the efficacy and safety of ESD for gastric superficial lesions in a European country. DESIGN Consecutive case-series report. SETTING A tertiary specialized center. PATIENTS Nineteen patients with gastric superficial lesions (15-30 mm), with high-grade (n = 15) or low-grade (n = 4) noninvasive epithelial neoplasias, in the antrum (n = 12), incisura angularis (n = 2), body (n = 3), and cardia (n = 2). INTERVENTION ESD with the patient under general anesthesia in the endoscopic room (40-300 minutes) by using an insulated-tip-knife. MAIN OUTCOME MEASUREMENTS Complete (R0) and en bloc resection, and complications. RESULTS ESD was achieved in all cases, with 89% R0 resection and 79% en bloc resection rates observed. Major bleeding was reported in 1 case (5%); there were no cases of perforation. With a median follow-up of 10 months, a single recurrence (5%) was observed. LIMITATIONS A small series at a single center, with a short median follow-up time. CONCLUSION We report the feasibility and effectiveness of gastric ESD in Europe. A further description of a Western series is expected, and guidelines for its dissemination are desirable to define the role of this technique in Western countries.
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Affiliation(s)
- Mario Dinis-Ribeiro
- Department of Gastroenterology, Portuguese Oncology Institute, Porto, Portugal
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17
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Lima-Ramos V, Pacheco-Figueiredo L, Costa S, Pardal F, Silva A, Amorim J, Lopes JM, Reis RM. TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant therapy response of gliomas. ACTA ACUST UNITED AC 2008; 180:14-9. [PMID: 18068527 DOI: 10.1016/j.cancergencyto.2007.08.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Accepted: 08/31/2007] [Indexed: 10/22/2022]
Abstract
TP53 is a key tumor suppressor gene that encodes a transcriptional factor involved in several cellular mechanisms, including growth arrest, DNA repair, and induction of apoptosis. In addition to TP53 gene mutations, a common polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The Pro72 variant has been associated with a slower induction of apoptosis and may influence the risk of cancer development. The role of Arg72Pro polymorphism in glioma susceptibility is poorly characterized. With the objective of analyzing the role of the TP53 Arg72Pro polymorphism in glioma risk, overall survival, and patient therapy response in a Portuguese population, we conducted a retrospective case-control study, including 171 patients with gliomas and 526 cancer-free individuals. The Arg72Pro genotype was assessed by the polymerase chain reaction-restriction fragment length polymorphism technique. No statistically significant differences were observed in the genotypic and allelic frequencies between glioma and control groups, and no statistically significant differences were observed with stratification of gliomas into distinct histological subtypes: astrocytic (n = 115), glioblastoma (n = 75), and oligodendroglial (n = 54) tumors. No significant association was observed between TP53 Arg72Pro and patient overall survival, but Kaplan-Meier analysis of glioma patients harboring the Pro72 allele showed a significantly longer survival with adjuvant therapy. In this first assessment of the role of TP53 Arg72Pro polymorphism in a large series of Portuguese glioma tumors, no association was observed with glioma susceptibility or overall survival, except for patients submitted to adjuvant therapy.
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Affiliation(s)
- Vítor Lima-Ramos
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Braga, Portugal
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18
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Pista A, Oliveira A, Barateiro A, Costa H, Verdasca N, Paixão MT. Molecular variants of human papillomavirus type 16 and 18 and risk for cervical neoplasia in Portugal. J Med Virol 2007; 79:1889-97. [PMID: 17935194 DOI: 10.1002/jmv.21002] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non-European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies.
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Affiliation(s)
- Angela Pista
- Papillomavirus Unit, Centre of Virology, National Institute of Health, Lisboa, Portugal.
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Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, Moreira-Dias L. Feasibility and cost-effectiveness of using magnification chromoendoscopy and pepsinogen serum levels for the follow-up of patients with atrophic chronic gastritis and intestinal metaplasia. J Gastroenterol Hepatol 2007; 22:1594-604. [PMID: 17845687 DOI: 10.1111/j.1440-1746.2007.04863.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen. METHODS A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed. RESULTS A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia. CONCLUSIONS The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.
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Affiliation(s)
- Mário Dinis-Ribeiro
- Department of Gastroenterology, Portuguese Oncology Institute, Porto, Portugal.
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Costa S, Pinto D, Pereira D, Rodrigues H, Cameselle-Teijeiro J, Medeiros R, Schmitt F. XRCC1 Arg399Gln and RAD51 5'UTR G135C polymorphisms and their outcome in tumor aggressiveness and survival of Portuguese breast cancer patients. Breast Cancer Res Treat 2007; 109:183-5. [PMID: 17616806 DOI: 10.1007/s10549-007-9637-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2007] [Accepted: 05/30/2007] [Indexed: 11/27/2022]
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21
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Payne S. Not an equal opportunity disease – a sex and gender-based review of colorectal cancer in men and women: Part I. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/j.jmhg.2007.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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22
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Costa S, Pinto D, Pereira D, Rodrigues H, Cameselle-Teijeiro J, Medeiros R, Schmitt F. DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population. Breast Cancer Res Treat 2006; 103:209-17. [PMID: 17063276 DOI: 10.1007/s10549-006-9364-z] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2006] [Accepted: 08/01/2006] [Indexed: 10/24/2022]
Abstract
The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects, for XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1 399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI 0.35-0.84; p = 0.006). Furthermore, we found that carriers of XRCC3 241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42-3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51 135C genotypes (OR = 2.17 95% CI 1.19-3.98; p = 0.012). Our results suggest XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51 G135C polymorphism as a real risk modifier in familial breast cancer cases.
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Affiliation(s)
- Sandra Costa
- ICVS, Life and Health Sciences Research Institute, Health Science School, Minho University, Braga, 4710-057, Portugal
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23
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Pereira C, Sousa H, Ferreira P, Fragoso M, Moreira-Dias L, Lopes C, Medeiros R, Dinis-Ribeiro M. -765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol 2006; 12:5473-8. [PMID: 17006983 PMCID: PMC4088228 DOI: 10.3748/wjg.v12.i34.5473] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma.
METHODS: A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method.
RESULTS: -765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%). Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).
CONCLUSION: -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.
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Affiliation(s)
- Carina Pereira
- Serviço de Gastrenterologia, Instituto Português de Oncologia do Porto FG EPE, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
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24
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Pinto-Correia AL, Sousa H, Fragoso M, Moreira-Dias L, Lopes C, Medeiros R, Dinis-Ribeiro M. Gastric cancer in a Caucasian population: Role of pepsinogen C genetic variants. World J Gastroenterol 2006; 12:5033-6. [PMID: 16937501 PMCID: PMC4087408 DOI: 10.3748/wjg.v12.i31.5033] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions.
METHODS: The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp).
RESULTS: Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P < 0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P < 0.001) or invasive GC (OR = 0.39; P = 0.004).
CONCLUSION: Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.
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Abstract
Early diagnosis represents the most important measure to decrease gastric cancer mortality. Endoscopists should be trained to perform standardized extremely rigorous observation with a low threshold of suspicion for neoplasia. Together with recent interest in new imaging techniques such as magnification, chromoendoscopy should be considered to represent a simple, safe and inexpensive technique that may be useful in identifying premalignant conditions and minute cancerous lesions, estimating their superficial extent and determining the histological type and submucosal invasion.
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Affiliation(s)
- Mário Dinis-Ribeiro
- Department of Gastroenterology, Instituto Português de Oncologia Francisco Gentil, Porto, Portugal.
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26
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Santos AM, Sousa H, Pinto D, Portela C, Pereira D, Catarino R, Duarte I, Lopes C, Medeiros R. Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer. Eur J Cancer 2006; 42:958-63. [PMID: 16542834 DOI: 10.1016/j.ejca.2006.01.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2005] [Revised: 12/20/2005] [Accepted: 01/03/2006] [Indexed: 11/22/2022]
Abstract
TP53 and its downstream effector gene P21 are two important genes in cell cycle regulation. Genetic alterations on p53 and attenuation of p21 expression result in progression through cell cycle G1 checkpoint, which can lead to cancer development. We analysed the frequency of TP53 codon 72 and 3'UTR P21 polymorphisms in 681 blood samples from 371 cervical cancer patients, 122 ovarian cancer patients and 188 healthy controls using AS-PCR and PCR-RFLP. Approximately twofold increased risk of ovarian cancer (OC) was observed for TP53 Pro carriers (P = 0.038), with a significantly higher risk for advanced OC (P = 0.018). Furthermore, among the P21 CC genotypes, TP53 P allele was also associated with a twofold increased risk of OC (P = 0.014) and to a threefold increased risk for advanced OC (P = 0.003) with an attributable proportion of 44.2%. These results were confirmed in an age-adjusted logistic regression analysis. No association was found between these polymorphisms and cervical cancer. Our results suggest that the TP53 codon 72 genotypes may be considered as a molecular marker, contributing to a genetic profile for ovarian cancer in women.
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Affiliation(s)
- Alexandra M Santos
- Molecular Oncology Unit, Portuguese Institute of Oncology-Oporto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal.
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Ferreira PM, Catarino R, Pereira D, Matos A, Pinto D, Coelho A, Lopes C, Medeiros R. Cervical cancer and CYP2E1 polymorphisms: implications for molecular epidemiology. Eur J Clin Pharmacol 2005; 62:15-21. [PMID: 16372174 DOI: 10.1007/s00228-005-0066-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2005] [Accepted: 11/11/2005] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Besides human papillomavirus (HPV) infection, several cofactors are considered important for the development of cervical cancer (CC). Among these, tobacco smoke, other sexually transmitted diseases, inflammation and nutritional factors have been intensively described. CYP2E1 polymorphisms have been associated with the metabolization of several carcinogens, some of them considered risk factors for CC development, such as tobacco smoke. The aim of this study was to evaluate the role of CYP2E1 polymorphisms in the susceptibility to cervical cancer in a Portuguese population. PATIENTS AND METHODS The genotypic analysis was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, using peripheral blood samples of 454 individuals: 122 presented invasive squamous cell carcinoma (ICC), 59 presented squamous intraepithelial lesions (SIL), and the control population was composed of 274 healthy individuals. RESULTS Concerning the DraI polymorphism, we observed a decreased risk for the development of squamous cervical lesions in the presence of the C allele [odds ratio (OR)=0.600; 0.378<OR<0.952; p=0.029]. In the stratification of the analysis according to the mean age, we observed an increased risk for the development of SIL, for women older than 39 years of age, in the presence of the D allele (OR=0.087; 0.012<OR<0.651; p=0.003). Regarding the RsaI polymorphism, we did not find any significant differences. CONCLUSION The decreased risk observed for the development of SIL and not ICC in the presence of the D allele may indicate that CYP2E1 interferes with the initial steps of the carcinogenic process, probably due to its involvement in the action of immunological mediators, expressed during cervical inflammation. These aspects may help to define new therapeutic strategies for chemoprevention.
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Affiliation(s)
- Paula M Ferreira
- Oncologia Molecular-Laboratórios, Instituto Português de Oncologia-Porto, Piso 4, Rua Dr António Bernardino de Almeida, 4200-072, Porto, Portugal
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28
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Santos AM, Sousa H, Portela C, Pereira D, Pinto D, Catarino R, Rodrigues C, Araújo AP, Lopes C, Medeiros R. TP53 and P21 polymorphisms: response to cisplatinum/paclitaxel-based chemotherapy in ovarian cancer. Biochem Biophys Res Commun 2005; 340:256-62. [PMID: 16364249 DOI: 10.1016/j.bbrc.2005.11.176] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2005] [Accepted: 11/22/2005] [Indexed: 12/12/2022]
Abstract
Ovarian cancer (OC) is the most lethal gynaecologic cancer and its standard treatment consists of platinum-based chemotherapy after cytoreductive surgery. The p53 protein plays a critical role on different cellular processes in response to DNA damage and it is responsible for transcriptional induction of the P21 gene. We have analysed 114 blood samples in order to investigate the effect of the TP53 codon 72 and the P21 3'UTR polymorphisms in response to cisplatinum/paclitaxel chemotherapy for OC treatment. The genotypes of the TP53 codon 72 and P21 3'UTR polymorphism were identified using AS-PCR and PCR-RFLP, respectively. Our results indicate that the TP53 P allele is associated with a worse prognosis (P=0.011) while P21 polymorphism genotypes did not reveal any statistically significant result (P>0.05). Furthermore, simultaneous carriers of the TP53 AA genotype and the P21 CC genotype demonstrate a longer progression-free interval (P=0.020). This study suggests that the characterisation of a genetic profile can contribute to the definition of a better chemotherapy treatment.
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Affiliation(s)
- Alexandra M Santos
- Molecular Oncology Unit, Portuguese Institute of Oncology-Oporto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal.
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Pinto D, Pereira D, Portela C, da Silva JL, Lopes C, Medeiros R. The influence of HER2 genotypes as molecular markers in ovarian cancer outcome. Biochem Biophys Res Commun 2005; 335:1173-8. [PMID: 16112085 DOI: 10.1016/j.bbrc.2005.08.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2005] [Accepted: 08/02/2005] [Indexed: 12/29/2022]
Abstract
A relevant clinical problem in the treatment of ovarian cancer (OC) is the development of resistance to chemotherapy, frequently due to genetic variations in enzymes and receptors. Changes in the HER2 receptor have been associated with breast and ovarian cancers. The role of a polymorphism in the HER2 gene in the clinical outcome of OC patients was investigated in this study. We characterized DNA samples from 111 patients with OC treated with cisplatin and paclitaxel, using PCR-RFLP. Our results indicate that patients carrying the valine homozygotic genotype present a lower overall survival mean, suggesting a role for this polymorphism in the outcome of ovarian cancer patients. The G allele has been implicated in the formation of active HER2 receptors, with a more aggressive phenotype. We hypothesize that HER2 genotypes can be predictive biomarkers in ovarian cancer, contributing to a genetic individual profile of great interest in clinical oncology.
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Affiliation(s)
- Daniela Pinto
- Pathology and Molecular Oncology Unit, Portuguese Institute of Oncology, Porto, Portugal.
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30
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Medeiros R, Prazeres H, Pinto D, Macedo-Pinto I, Lacerda M, Lopes C, Cruz E. Characterization of HPV genotype profile in squamous cervical lesions in Portugal, a southern European population at high risk of cervical cancer. Eur J Cancer Prev 2005; 14:467-71. [PMID: 16175051 DOI: 10.1097/01.cej.0000178079.29533.1e] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
A different prevalence of human papillomavirus (HPV) types has been reported in distinct populations. Although Portugal has a relatively high incidence of cervical cancer within the European Union, no studies have been reported in the Portuguese population. Recently, a clinical trial using a vaccine targeted against HPV-16 demonstrated a high efficacy in preventing HPV-16 cervical lesions. The aim of the present study was the characterization of HPV genotype profile in squamous intraepithelial lesions (SIL) and invasive cervical cancer (ICC) from 608 patients using polymerase chain reaction (PCR) methodology. We frequently detected HPV-6/11 and HPV-16 in low-grade SIL (HPV-6/11, 18.9%; HPV-16, 44.2%). In high-grade SIL, HPV-16 was demonstrated in 74.2% of those lesions and in 80.0% of the cases with ICC. HPV-18 was found in 3.1%, 0.8% and in 15.0% of low, high SIL and ICC, respectively. The overall prevalence of multiple infections with high-risk HPV was 7.2%. Other types of HPV were detected in 7.0% of all cases. Our results demonstrate a high prevalence of HPV-16 in SIL and ICC in Portuguese women. Therefore, a prophylactic HPV-16/18 vaccine may be effective in the prevention of cervical cancer in a significant number of women from this southern European population.
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Affiliation(s)
- R Medeiros
- Instituto Português de Oncologia-Centro Regional de Oncologia do Porto, Laboratórios - Piso 4, R. Dr. António Bernardino de Almeida, 4200-072 Portugal.
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Matos A, Moutinho J, Pinto D, Medeiros R. The influence of smoking and other cofactors on the time to onset to cervical cancer in a southern European population. Eur J Cancer Prev 2005; 14:485-91. [PMID: 16175054 DOI: 10.1097/01.cej.0000174780.44260.32] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Cervical cancer is a complex and multifactorial disease. Although there are substantial data supporting the causative role of persistent human papillomavirus (HPV) infection in the development of cervical cancer, the complete course of the disease has never been completely understood. Several risk cofactors have been suggested with controversial results. Portugal has the highest incidence of squamous cell carcinoma (SCC) within western Europe and there are no known studies regarding the role of cofactors in SCC. The aim of our study was to evaluate the role of smoking, sexual behaviour, reproductive and contraceptive history, in the time-to-onset (TTO) of severe cervical lesions (HGSIL/SCC) in the Portuguese population. We verified that age of first sexual intercourse under 18 years (odds ratio (OR) 2.8), pregnancy (OR 2.9), first pregnancy under 21 years (2.6), number of pregnancies (OR 2.3-5.4) and parity (OR 1.9-5.7) are risk factors in the development of cervical neoplasia. Smoke exposure index (SEI) was significantly different (P=0.002) between cases and controls. Our results regarding time-to-onset demonstrate that smoking (P<0.001, log rank test), number of sexual partners (P<0.001, log rank test) and use of oral contraceptives (P<0.001, log rank test) are important determinants in the earlier onset of severe cervical lesions. Using this approach, our findings may help to clarify the role of smoking and other cofactors in the persistence and progression of cervical lesions.
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Affiliation(s)
- A Matos
- Molecular Oncology Unit and Gynaecology Department, Instituto Português de Oncologia, Porto 4200-072, Portugal
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Duarte I, Santos A, Sousa H, Catarino R, Pinto D, Matos A, Pereira D, Moutinho J, Canedo P, Machado JC, Medeiros R. G-308A TNF-alpha polymorphism is associated with an increased risk of invasive cervical cancer. Biochem Biophys Res Commun 2005; 334:588-92. [PMID: 16009345 DOI: 10.1016/j.bbrc.2005.06.137] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2005] [Accepted: 06/23/2005] [Indexed: 01/22/2023]
Abstract
Cervical cancer is initiated by high-risk human papillomaviruses (HPV-16 and HPV-18), but an effective immune response may control the progression of this disease. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, that has been implicated in several cancers. In a case-control study, we evaluated the association between the G-308A TNF-alpha promoter polymorphism and the risk for invasive cervical cancer (ICC). TNF-alpha polymorphism was analyzed by PCR-RFLP and confirmed by sequencing. DNA was obtained from blood samples of 439 individuals, including 195 patients with ICC and 244 normal healthy controls. According to our results, women carrying the A allele present a twofold increased risk of developing ICC (p=0.006; OR=1.88; 95% CI [1.20-2.94]). In conclusion, our study suggests that the presence of the high producer allele -308A in the TNF-alpha gene appears to be associated with an increased risk for the development of ICC.
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Affiliation(s)
- Isabel Duarte
- Molecular Oncology Laboratory, Portuguese Institute of Oncology, Porto, Portugal.
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Costa S, Pinto D, Morais A, Vasconcelos A, Oliveira J, Lopes C, Medeiros R. Acetylation genotype and the genetic susceptibility to prostate cancer in a southern European population. Prostate 2005; 64:246-52. [PMID: 15717312 DOI: 10.1002/pros.20241] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Epidemiologic studies have suggested that environmental factors and diet are important risk factors in the pathogenesis of prostate cancer. The N-acetyltransferases (NAT) are important enzymes in activation and inactivation of various carcinogens, including those found in well-cooked meat and cigarette smoke. METHODS We analyzed DNA samples from 146 prostate cancer patients and 174 healthy men. We used PCR-RFLP method to analyze NAT 1 and NAT 2 polymorphisms. RESULTS We did not find statistically significant differences in NAT 1 genotypes frequencies between prostate cancer patients and control group. We observed an association of the slow acetylator genotype, NAT 2*6/NAT2*6 with prostate cancer protection (P=0.017; OR=0.31, 95% CI 0.11--0.84). Multivariate logistic regression analysis confirmed this association (0.030; OR=0.32, 95% CI 0.12--0.89). CONCLUSIONS Our results indicate a role of NAT2 polymorphisms in the carcinogenic pathway of prostate cancer, specifically in a population of Southern Europe.
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Affiliation(s)
- Sandra Costa
- ICVS, Life and Health Sciences Research Institute, Health Science School, Minho University, Braga, Portugal.
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Santos AM, Sousa H, Catarino R, Pinto D, Pereira D, Vasconcelos A, Matos A, Lopes C, Medeiros R. TP53 codon 72 polymorphism and risk for cervical cancer in Portugal. ACTA ACUST UNITED AC 2005; 159:143-7. [PMID: 15899386 DOI: 10.1016/j.cancergencyto.2004.10.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2004] [Accepted: 10/11/2004] [Indexed: 11/19/2022]
Abstract
High-risk human papillomavirus are essential for the development of cervical cancer; however, TP53 is the most frequently altered tumor suppressor gene among tumors and is described as a cofactor for cervical carcinogenesis. TP53 has two common polymorphic forms encoding either proline or arginine, at position 72, and the presence of homozygous arginine has been reported as a risk factor for cervical cancer in many populations. We evaluated the effect of this TP53 polymorphism in a northern Portuguese population. We analyzed blood samples of 385 women; 20 with low-grade squamous intraepithelial lesion (SIL), 56 with high-grade SIL, 164 with invasive cervical cancer, and 145 healthy controls, using allele specific-polymerase chain reaction methodology. We observed an increased frequency of the Arg/Arg genotype in the cancer group, but no statistical significance was found between cases and controls (P>0.05). Our results indicate that there is no association between the presence of the Arg allele in codon 72 of TP53 polymorphism and risk of cervical cancer in our population.
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Affiliation(s)
- Alexandra M Santos
- Molecular Oncology Unit, Portuguese Institute of Oncology-Porto, Laboratórios 4 Piso, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
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Catarino R, Matos A, Pinto D, Pereira D, Craveiro R, Vasconcelos A, Lopes C, Medeiros R. Increased risk of cervical cancer associated with cyclin D1 gene A870G polymorphism. ACTA ACUST UNITED AC 2005; 160:49-54. [PMID: 15949570 DOI: 10.1016/j.cancergencyto.2004.11.017] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2004] [Revised: 11/19/2004] [Accepted: 11/30/2004] [Indexed: 01/01/2023]
Abstract
Human papillomavirus (HPV) plays a major role in the etiology of cervical cancer. However, a complex correlation between viral and cellular genes is necessary for cell cycle control deregulation in the progression to invasive cervical cancer (ICC). Cyclin D1 (CCND1) is an important positive regulator of the G1/S phase of the cell cycle. The CCND1 gene is located at 11q13 and is often altered in human cancers. We analyzed the A870G CCND1 polymorphism by polymerase chain reaction/restriction fragment length polymorphism analysis in 246 women including 50 cases with high-grade squamous intraepithelial lesions of the cervix (HSIL), 93 with ICC, and 103 healthy women. The GG genotype was associated with a 4.32-fold higher risk for the development of HSIL [adjusted odds ratio (aOR)=4.32, 95% confidence interval (CI) 1.50-12.46, P=0.0067), and a 3.26-fold increased risk for the development of ICC (aOR=3.26, 95% CI 1.42-7.53, P=0.006). The proportion of cervical cancer cases attributable to the GG CCND1 genotype was 17.26%. This study indicates that the A870G CCND1 polymorphism could act as a cofactor of HPV in the initiation of cervical carcinogenesis, particularly in the transformation zone of HPV-infected women, supporting evidence for a genetic factor in ICC risk.
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Affiliation(s)
- Raquel Catarino
- Molecular Oncology Unit, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almedia, Porto 4200-072, Portugal
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Abstract
The city of São Paulo exhibits one of the highest incidences of laryngeal cancer in world and Brazil presents remarkable occurrence, compared with other Latin American countries. Around 8,000 new cases and 3,000 deaths by laryngeal cancer occur annually in the Brazilian population. In the city of São Paulo, incidence rates for laryngeal cancer among males have been decreasing since the late 1980s while, among females, the rates have shown a stable trend. This phenomenon is probably the expression of changes in gender behavior related to tobacco smoking. Several risk factors are involved in the genesis of laryngeal cancer. The most important are tobacco smoking and alcohol intake, but occupational hazards have also been associated with the disease, such as asbestos, strong inorganic acids, cement dust and free crystalline silica. Additionally, salted meat and total fat intake have been linked to elevated risk of laryngeal cancer. Conversely, several studies have confirmed that fruits, raw leaf vegetables and legumes protect against this cancer. Some researchers have postulated a possible association between laryngeal squamous cell carcinoma and human papilloma virus (HPV), but this is not universally accepted. Gastroesophageal reflux disease is weakly, but consistently correlated with laryngeal cancer. Familial cancer clusters, particularly of head and neck tumors, seem to increase the risk of laryngeal cancer. Some genetic polymorphisms, such as of genes that code for xenobiotic-metabolizing enzymes, have shown elevated risk for laryngeal cancer according to recent studies. Public health policies regarding the control of tobacco smoking and alcohol consumption, and also surveillance of carcinogen exposure in occupational settings, could have an impact on laryngeal cancer. No proposals for screening have been recommended for laryngeal cancer, but one diagnostic goal should be to avoid treatment delay when suspected symptoms have been observed.
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Affiliation(s)
- Victor Wünsch Filho
- Department of Epidemiology, Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil.
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Craveiro R, Costa S, Pinto D, Salgado L, Carvalho L, Castro C, Bravo I, Lopes C, Silva I, Medeiros R. TP73 alterations in cervical carcinoma. ACTA ACUST UNITED AC 2004; 150:116-21. [PMID: 15066318 DOI: 10.1016/j.cancergencyto.2003.08.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2003] [Revised: 08/26/2003] [Accepted: 08/27/2003] [Indexed: 12/27/2022]
Abstract
Infection with human papillomaviruses (HPV) is essential in the carcinogenesis of the uterine cervix. However, a complex interrelation between viral and cellular genes is necessary for cell-cycle control deregulation and development and progression of cervical cancer induction. The TP73 gene is localized in 1p36.3 band, which is often deleted by loss of heterozygosity (LOH) in human cancers. We analyzed the p73 cytosine thymine polymorphism and LOH in this locus by polymerase chain reaction restriction fragment length polymorphism in 134 DNA samples from biopsies of 67 primary untreated invasive cervix tumors and the corresponding peripheral blood. Genotype frequencies of 56.7% for homozygous genotype GC/GC and 43.3% for heterozygous genotype GC/AT were found. The presence of the GC/AT genotype in tumors was associated with lower age at menarche (P=0.039) and high parity (P=0.015). In 20.0% of DNA tumor samples, the AT allele was lost compared with their DNA normal blood pairs. The AT allele was conserved in women with high parity. This was not the case in the group with low parity, with 33.3% of patients showing loss of the AT allele in tumor DNA (P=0.041). These results suggest that TP73 genetic alterations may contribute to the genesis and/or progression of cervical carcinoma in an HPV-infected transformation zone under prolonged exposure to events related to pregnancy.
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Affiliation(s)
- Rogéria Craveiro
- Department of Radiotherapy, Instituto Português de Oncologia, Porto, Rua Dr. Ant. Bernardino Almeida, 4200-072 Porto, Portugal
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