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Association of adiponectin receptor 1 gene - 106 C > T variant with susceptibility to colorectal cancer.

ABSTRACT: BACKGROUND:Colorectal cancer (CRC) is the fourth leading cause of cancer-related death around the world and accumulated evidence indicates the association between CRC and obesity and insulin resistance. OBJECTIVES:Regarding the role of adiponectin in obesity and insulin resistance, we explored whether genetic variants in adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) are associated with CRC risk. MATERIALS AND METHODS:ADIPOQ (rs2241766) and ADIPOR1 (rs2275738) gene variants were genotyped in 261 cases with CRC and 339 controls using PCR-RFLP method. RESULTS:In this study, no significant difference was observed for ADIPOQ gene rs2241766 variant between the cases and controls. However, carriers of the ADIPOR1 (rs2275738) "CC + CT" genotype compared with "TT" genotype occurred more frequently in the cases with CRC than the controls, and the difference remained significant after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC (P = 0.048; OR = 1.49, 95%CI = 1.01-2.20). Interestingly, after adjustment for confounding factors the ADIPOR1 "CC + TC" genotype compared with "TT" genotype was also associated with an increased risk for obesity in the cases (P = 0.040; OR = 1.86, 95%CI = 1.03-3.36). CONCLUSIONS:Our findings suggest for the first time that the - 106 C > T (rs2275738) variant of ADIPOR1 gene may be a genetic contributor to CRC and obesity risk in the cases with CRC. However, further studies with bigger sample size are needed to validate these findings.

SUBMITTER: Mahmoudi T

PROVIDER: S-EPMC5006128 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Association of adiponectin receptor 1 gene - 106 C > T variant with susceptibility to colorectal cancer.

Mahmoudi Touraj T Karimi Khatoon K Karimi Negar N Farahani Hamid H Nobakht Hossein H Dabiri Reza R Vahedi Mohsen M Zali Mohammad Reza MR

Meta gene 20160714

<h4>Background</h4>Colorectal cancer (CRC) is the fourth leading cause of cancer-related death around the world and accumulated evidence indicates the association between CRC and obesity and insulin resistance.<h4>Objectives</h4>Regarding the role of adiponectin in obesity and insulin resistance, we explored whether genetic variants in adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) are associated with CRC risk.<h4>Materials and methods</h4>ADIPOQ (rs2241766) and ADIPOR1 (rs2275738) ge ...[more]

PMID: 27617220

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Project description:CONTEXT:Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. OBJECTIVE:To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. DESIGN, SETTING, AND PATIENTS:Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. MAIN OUTCOME MEASURES:ADIPOQ and ADIPOR1 SNP frequency among cases and controls. RESULTS:In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99). CONCLUSION:The SNP rs266729, which tags the 5' flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.

Dataset Information

Association of adiponectin receptor 1 gene - 106 C > T variant with susceptibility to colorectal cancer.

Publications

Association of adiponectin receptor 1 gene - 106 C > T variant with susceptibility to colorectal cancer.

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