Case-control study of diabetes-related genetic variants and pancreatic cancer risk in Japan

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 46; pp. 17456 - 17462
• Main Authors: Kuruma, Sawako, Egawa, Naoto, Kurata, Masanao, Honda, Goro, Kamisawa, Terumi, Ueda, Junko, Ishii, Hiroshi, Ueno, Makoto, Nakao, Haruhisa, Mori, Mitsuru, Matsuo, Keitaro, Hosono, Satoyo, Ohkawa, Shinichi, Wakai, Kenji, Nakamura, Kozue, Tamakoshi, Akiko, Nojima, Masanori, Takahashi, Mami, Shimada, Kazuaki, Nishiyama, Takeshi, Kikuchi, Shogo, Lin, Yingsong
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.12.2014
• Subjects: Adiponectin - genetics; Aged; Asian Continental Ancestry Group - genetics; Carcinoma, Pancreatic Ductal - diagnosis; Carcinoma, Pancreatic Ductal - ethnology; Carcinoma, Pancreatic Ductal - genetics; Case Control Study; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus - diagnosis; Diabetes Mellitus - ethnology; Diabetes Mellitus - genetics; Female; Gene Frequency; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Japan - epidemiology; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - ethnology; Pancreatic Neoplasms - genetics; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Japan; Case-control study; Odds ratio; Risk; Single-nucleotide polymorphisms; Pancreatic cancer
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i46.17456

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