Adiponectin gene and risk of colorectal cancer

Department of Human Genetics, University of Michigan School of Medicine, 1524 BSRB, 109 Zina Pitcher, Ann Arbor, MI, USA.
British Journal of Cancer (Impact Factor: 4.82). 08/2011; 105(4):562-4. DOI: 10.1038/bjc.2011.259
Source: PubMed

ABSTRACT Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.
The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case-control study in Israel.
No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88-1.23.
The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel.

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    ABSTRACT: Some studies have observed a lower circulating level of adiponectin in cancer patients, but whether this observation is causal remains unresolved. We therefore undertook a meta-analysis implementing Mendelian randomization to exploit the causal relevance of circulating adiponectin with cancer by using multiple polymorphisms in adiponectin encoded gene ADIPOQ as instrumental variables. Eligible articles were identified from PubMed and Embase. Data and study quality were assessed in duplicate. Total 26 articles including 31 study groups were analyzed. Overall allelic association with cancer was significant for rs822396 (odds ratio (OR) = 0.91; P = 0.045) and rs1501299 (OR = 0.89; P = 0.051), with low or moderate heterogeneity. Carriers of rs2241766 GG genotype (weighted mean difference (WMD) = 0.86; P = 0.037) or G allele (WMD = 0.68; P = 0.047) had significantly higher circulating adiponectin than the TT genotype carriers, without heterogeneity. Using rs2241766 as an instrument in Mendelian randomization analysis, an increment of 1 mg/L in circulating adiponectin was significantly associated with a 43-50 % reduced risk for lung cancer, but with a 20-40 % increased risk of colorectal cancer, respectively. There was no observable publication bias. Genetically elevated circulating adiponectin might confer a protective effect against lung cancer, yet a risky effect for colorectal cancer. Further validation is urgently required.
    Tumor Biology 10/2014; 36(2). DOI:10.1007/s13277-014-2654-x · 2.84 Impact Factor
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    ABSTRACT: Background Epidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADIPOR1 and the CRC risk with a hospital-based case-control study in the Chinese population along with meta-analysis of available epidemiological studies.Methods With a hospital-based case-control study of 341 cases and 727 controls, the associations between the common variants on ADIPOQ (rs266729, rs822395, rs2241766 and rs1501299) and ADIPOR1 (rs1342387 and rs12733285) and CRC susceptibility were evaluated. Meta-analysis of the published epidemiological studies was performed to investigate the associations between the variants and CRC risk.ResultsFor the population study, we found that variant rs1342387 of ADIPOR1 was associated with a reduced risk for CRC [adjusted odds ratio (OR)¿=¿0.74, 95% confidential intervals (95% CI)¿=¿0.57-0.97; CT/TT vs. CC]. The meta-analysis also suggested a significant association for rs1342387 and CRC risk; the pooled OR was 0.79 (95% CI¿=¿0.66-0.95) for the CT/TT carriers compared to CC homozygotes under the random-effects model (Q¿=¿8.06, df¿=¿4, P¿=¿0.089; I2¿=¿50.4%). The case-control study found no significant association for variants rs266729, rs822395, rs2241766, and rs1501299 on ADIPOQ or variant rs12733285 on ADIPOR1 and CRC susceptibility, which were consistent with results from the meta-analysis studies.Conclusions These data suggested that variant rs1342387 on ADIPOR1 may be a novel CRC susceptibility factor.
    BMC Medical Genetics 12/2014; 15(1):137. DOI:10.1186/s12881-014-0137-y · 2.45 Impact Factor
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    Pathology - Research and Practice 11/2014; 211(4). DOI:10.1016/j.prp.2014.11.012 · 1.56 Impact Factor

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