Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

I Yamada ,Naoto Egawa,Keitaro Matsuo,Masato Ozaka,Hiroshi Ishii,Satoyo Hosono,Dai Inoue,Kenji Wakai,Haruhisa Nakao,Kiyoko Yagyu,Shogo Kikuchi,Mami Takahashi,Sawako Kuruma,Takeshi Nishiyama,Akiko Tamakoshi,Yusuke Muramatsu,Shinichi Ohkawa,Kozue Nakamura,Makoto Ueno,Masato Matsuyama,Mitsuru Mori,Yingsong Lin,Kazuaki Shimada,Junji Ueda ,Masanori Nojima

doi:10.7314/apjcp.2014.15.1.391

I Yamada , Naoto Egawa + Show 23 more

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https://doi.org/10.7314/apjcp.2014.15.1.391

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Abstract

We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

Highlights

The etiology of pancreatic cancer remains largely unknown
Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules
We examined the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1 in Japanese subjects, using a hospital-based case-control study

Summary

Introduction

The etiology of pancreatic cancer remains largely unknown. Epidemiologic studies have consistently shown positive associations between pancreatic cancer with cigarette smoking and long-standing diabetes (Duell, 2012; Ben et al, 2011). We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study

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