title: Gene Polymorphisms of ADIPOQ +45T>G, UCP2 -866G>A, and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study.
abstract: As insulin resistance (IR) is an established risk factor for colorectal cancer (CRC), we explored the association between each of the IR-related gene polymorphisms of adiponectin (ADIPOQ) rs2241766, uncoupling protein 2 (UCP2) rs659366, and fatty acid-binding protein (FABP2) rs1799883 and CRC risk. Genotyping of blood samples and collection of lifestyle and dietary habits were performed for 400 case-control pairs. Unconditional logistic regression (ULR) was applied to assess the effects of the three single nucleotide polymorphisms (SNP), environmental factors. Both ULR and generalized multifactor dimensionality reduction (GMDR) were used to test the gene-gene and gene-environment interactions on CRC risk. Subjects carrying the ADIPOQ rs2241766 TG+GG genotype had a higher CRC risk than those carrying the TT genotype (OR = 1.429, 95% CI 1.069-1.909). The additive and multiplicative interactions between ADIPOQ rs2241766 and FABP2 rs1799883 on CRC were found by ULR (RERI = 0.764, 95%CI 0.218∼1.311, AP = 0.514, 95%CI 0.165∼0.864, S = -1.745, 95%CI is unachievable, and Pmulti = 0.017, respectively). Furthermore, the high order gene-gene interaction of the three SNPs were found by GMDR (P = 0.0107). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (Ptrend = 0.037). In GMDR, the gene-environment interaction among the three SNPs and red meat consumption on CRC risk was significant (P = 0.0107). Compared with subjects with low red meat consumption and null risk genotypes, those with high-red meat consumption and three risk genotypes had 3.439-fold CRC risk (95% CI 1.410-8.385). In conclusion, the results showed that the ADIPOQ rs2241766 TG+GG genotype increased CRC risk. Given the complexity of the carcinogen for CRC, ADIPOQ rs2241766, UCP2 rs659366, FABP2 rs1799883 and red meat consumption potentially worked together in affecting CRC risk.
authors.affiliation: Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Wenhui
authors.initials: W
authors.lastname: Liu
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D004843:Epistasis, Genetic; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000069466:Red Meat / Q000009:adverse effects; D000071246:Uncoupling Protein 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2