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.
Highlights
Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide [1]
The gene-gene and gene-environment interaction is a hot topic in genetic epidemiology [25,26,27], we explored the association of insulin resistance (IR)-related gene polymorphisms and CRC risk to identify susceptible genes and observe the gene-gene and gene-red meat consumption interaction on CRC
Unconditional logistic regression (ULR) indicated that having a family history of CRC and longer sitting hours per day ($8 hours/day) were associated with increased CRC risk (OR = 3.808, 95% confidence intervals (CI) 1.775–8.171 and odds ratios (OR) = 1.810, 95% CI 1.250–2.620, respectively), whereas habitual tea drinking decreased CRC risk (OR = 0.617, 95% CI 0.451–0.844)
Summary
Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide [1]. Considering the westernization of dietary habits and lifestyle changes, the incident rates of CRC in Eastern Asia and in Eastern Europe, which historically had the lowest rates, have remarkably increased in recent years [2]. The mechanism of CRC remains unclear, many researchers have suggested that environmental and genetic factors work together on the proliferation of CRC [4]. Western dietary habits, such as high-red meat consumption [5], and a sedentary lifestyle have been proven to play important roles in the development of CRC [6]. In the 1990s, McKeown-Eyssen [11] and Giovannucci [12] originally proposed a hypothesis of ‘‘insulin resistance-colon cancer’’
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