Brief Article
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World J Gastroenterol. Jul 7, 2013; 19(25): 4023-4030
Published online Jul 7, 2013. doi: 10.3748/wjg.v19.i25.4023
CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men
Tadamichi Hamachi, Osamu Tajima, Kousaku Uezono, Shinji Tabata, Hiroshi Abe, Keizo Ohnaka, Suminori Kono
Tadamichi Hamachi, Suminori Kono, Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Osamu Tajima, Kousaku Uezono, Self Defense Forces Kumamoto Hospital, Kumamoto 862-0902, Japan
Tadamichi Hamachi, Shinji Tabata, Hiroshi Abe, Self Defense Forces Fukuoka Hospital, Kasuga-shi, Fukuoka 816-0826, Japan
Keizo Ohnaka, Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Author contributions: Hamachi T performed data analysis and prepared the draft manuscript; Tajima O, Uezono K, Tabata S and Abe H were in charge of study design and implementation of the survey; Ohnaka K contributed to genotyping and statistical analysis; Kono S was in charge of the whole process including preparation of the manuscript; all authors contributed to interpretation of the results and critical revision of the manuscript for intellectual content, and they read and approved the final manuscript.
Supported by The Scientific Support Programs for Cancer Research, Grant-in-Aid for Scientific Research on Innovative Areas, No. 221S0001; the Ministry of Education, Culture, Sports, Science and Technology, Japan
Correspondence to: Dr. Suminori Kono, Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. skono@phealth.med.kyushu-u.ac.jp
Telephone: +81-92-6426110 Fax: +81-92-6426115
Received: January 27, 2013
Revised: April 13, 2013
Accepted: April 18, 2013
Published online: July 7, 2013
Abstract

AIM: To investigate the role of functional genetic polymorphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas.

METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied were CYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other lifestyle factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test.

RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There was no measurable effect modification of smoking even regarding the combination of the genetic polymorphisms of the phase I and phase II enzymes.

CONCLUSION: Combination of the CYP1A1*2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status.

Keywords: Colorectal adenoma, Smoking, Polymorphism, CYP1A1, GSTM1, GSTT1, NQO1

Core tip: The study investigated the associations of CYP1A1*2A, CYP1A1*2C, GSTM1, GSTT1 and NQO1 C609T polymorphisms with colorectal adenomas among 455 cases of colorectal adenomas and 1052 controls with no polyps. None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1. Combination of the CYP1A1*2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status.