Abstract
Although their functional outcomes remain largely unknown, single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated gene (FTO) may interact with adipokines, especially leptin and adiponectin, to modify the risk of colorectal cancer. We conducted a prospective study of 375 colorectal cancer cases and 750 matched controls to examine the effects of SNPs in the FTO, either alone or in interaction with pre-diagnostic plasma adipokine levels. Using a conditional logistic regression model, we obtained odds ratios (ORs) and their 95% confidence intervals (CIs) of colorectal cancer. Seven SNPs in strong linkage disequilibrium demonstrated a similarly positive association with colorectal cancer, and most evidently for rs1558902, rs8050136, rs3751812, and rs9939609 (Ptrend = 0.02). Of interest, we observed a statistically significant interaction of rs8050136 with plasma total adiponectin levels (Pinteraction = 0.03). Compared to non-carriers in the lowest quintile of plasma total adiponectin, A allele carriers in the same quintile showed a considerably elevated risk of colorectal cancer, with a body mass index-adjusted OR of 2.54 (95% CI, 1.36–4.75). This investigation of the interaction between SNPs in the FTO and pre-diagnostic plasma adipokine levels has revealed the importance of both genetic and hormonal factors associated with adiposity in colorectal carcinogenesis.
Highlights
A variety of genome-wide association studies (GWAS) have robustly linked a cluster of single nucleotide polymorphisms (SNPs) in the first intron of the fat mass and obesity-associated gene to obesity [1,2,3], which is a well-established risk factor for certain types of malignancies, including colorectal cancer [4]
The purpose and methods of the study were communicated to the research participants, and consent was obtained implicitly when they responded to the baseline questionnaire and/or donated their blood samples
We investigated the association of SNPs in the fat mass and obesity-associated gene (FTO) gene and plasma concentrations of adipokines with the incidence of colorectal cancer
Summary
A variety of genome-wide association studies (GWAS) have robustly linked a cluster of single nucleotide polymorphisms (SNPs) in the first intron of the fat mass and obesity-associated gene (commonly abbreviated as FTO) to obesity [1,2,3], which is a well-established risk factor for certain types of malignancies, including colorectal cancer [4].
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