Case Control Study
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World J Gastroenterol. Dec 14, 2014; 20(46): 17456-17462
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17456
Case-control study of diabetes-related genetic variants and pancreatic cancer risk in Japan
Sawako Kuruma, Naoto Egawa, Masanao Kurata, Goro Honda, Terumi Kamisawa, Junko Ueda, Hiroshi Ishii, Makoto Ueno, Haruhisa Nakao, Mitsuru Mori, Keitaro Matsuo, Satoyo Hosono, Shinichi Ohkawa, Kenji Wakai, Kozue Nakamura, Akiko Tamakoshi, Masanori Nojima, Mami Takahashi, Kazuaki Shimada, Takeshi Nishiyama, Shogo Kikuchi, Yingsong Lin
Sawako Kuruma, Terumi Kamisawa, Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan
Naoto Egawa, Tokyo Metropolitan Ohtsuka Hospital, Tokyo 170-8476, Japan
Masanao Kurata, Goro Honda, Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan
Junko Ueda, Takeshi Nishiyama, Shogo Kikuchi, Yingsong Lin, Department of Public Health, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan
Hiroshi Ishii, Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo 135-8550, Japan
Makoto Ueno, Shinichi Ohkawa, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa 241-8515, Japan
Haruhisa Nakao, Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan
Mitsuru Mori, Masanori Nojima, Department of Public Health, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
Keitaro Matsuo, Department of Preventive Medicine, Kyushu University Faculty of Medical Science, Fukuoka 812-8582, Japan
Satoyo Hosono, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
Kenji Wakai, Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Kozue Nakamura, Department of Food and Nutrition, Gifu City Women’s College, Gifu 501-2592, Japan
Akiko Tamakoshi, Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
Mami Takahashi, Central Animal Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Kazuaki Shimada, Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan
Author contributions: Kikuchi S supervised the study; Kikuchi S, Lin Y, Kuruma S, Egawa N, Wakai K, Nakamura K, Tamakoshi A, Takahashi M and Shimada K designed the research; Kuruma S, Egawa N, Lin Y and Nishiyama T drafted the manuscript and conducted the statistical analysis; Ueda J, Hosono S and Matsuo K performed genotyping and SNP data analysis; Kuruma S, Egawa N, Kurata M, Honda G, Kamisawa T, Ishii H, Ueno M, Nakao H, Mori M, Ohkawa S and Nojima M participated in data collection; all authors read and approved the final manuscript.
Supported by Grants-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan
Correspondence to: Dr. Yingsong Lin, Department of Public Health, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, 480-1195, Japan. linys@aichi-med-u.ac.jp
Telephone: +81-561-623311 Fax: +81-561-625270
Received: March 4, 2014
Revised: April 18, 2014
Accepted: July 24, 2014
Published online: December 14, 2014
Abstract

AIM: To examine whether diabetes-related genetic variants are associated with pancreatic cancer risk.

METHODS: We genotyped 7 single-nucleotide polymorphisms (SNPs) in PPARG2 (rs1801282), ADIPOQ (rs1501299), ADRB3 (rs4994), KCNQ1 (rs2237895), KCNJ11 (rs5219), TCF7L2 (rs7903146), and CDKAL1 (rs2206734), and examined their associations with pancreatic cancer risk in a multi-institute case-control study including 360 cases and 400 controls in Japan. A self-administered questionnaire was used to collect detailed information on lifestyle factors. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between these diabetes-associated variants and pancreatic cancer risk.

RESULTS: With the exception of rs1501299 in the ADIPOQ gene (P = 0.09), no apparent differences in genotype frequencies were observed between cases and controls. Rs1501299 in the ADPIOQ gene was positively associated with pancreatic cancer risk; compared with individuals with the AA genotype, the age- and sex-adjusted OR was 1.79 (95%CI: 0.98-3.25) among those with the AC genotype and 1.86 (95%CI: 1.03-3.38) among those with the CC genotype. The ORs remained similar after additional adjustment for body mass index and cigarette smoking. In contrast, rs2237895 in the KCNQ1 gene was inversely related to pancreatic cancer risk, with a multivariable-adjusted OR of 0.62 (0.37-1.04) among individuals with the CC genotype compared with the AA genotype. No significant associations were noted for other 5 SNPs.

CONCLUSION: Our case-control study indicates that rs1501299 in the ADIPOQ gene may be associated with pancreatic cancer risk. These findings should be replicated in additional studies.

Keywords: Single-nucleotide polymorphisms, Pancreatic cancer, Risk, Case-control study, Odds ratio

Core tip: Although it is likely that a common genetic background predisposes individuals to developing both diabetes and pancreatic cancer, very few molecular epidemiologic studies have addressed this issue. We therefore genotyped 7 diabetes-related genetic variants and found that rs1501299 in the ADIPOQ gene may be associated with pancreatic cancer risk. The role of adiponectin variants needs further study.