Interactions between Genetic Variants in the Adiponectin, Adiponectin Receptor 1 and Environmental Factors on the Risk of Colorectal Cancer

Abstract

BackgroundMetabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis.Methodology/Principal FindingsTo investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48–2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78–7.34), 3.18 (95%CI: 1.73–5.82) and 1.97 (95%CI: 1.27–3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18–fold (95%CI:0.89–fold to 1.58–fold), 1.87–fold (95%CI: 1.38–fold to2.54–fold) and 4.39–fold (95%CI: 2.75–fold to 7.01–fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P trend <0.0001).Conclusions/SignificanceOur results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.

Adiponectin Receptor 1 (ADIPOR1) rs1342387 Polymorphism and Risk of Cancer: a Meta-analysis

“…Beebe Dimmer et al (2010) did not discover the link between rs1342387 polymorphism and risk of prostate cancer in African American men. Li Liu et al (2011) did not observer the association between rs1342387 polymorphism and risk of colorectal cancer in Chinese.…”

“…A total of 8 literatures (11 studies) including 3, 738 cases and 4748 controls were identified in this meta-analysis (Kaklamani et al, 2008a;2008b;Beebe-Dimmer et al, 2010;He et al, 2011;Kaklamani et al, 2011;Liu et al, 2011;Ou, 2012;Zhang et al, 2012), and one of these literatures was doctoral dissertation (Ou, 2012). All of the 11 studies were case-control studies, nine of which were population-based and another two were hospital-based.…”

Five Common Haplotype-Tagging Variants of Adiponectin (ADIPOQ) and Cancer Susceptibility: A Meta-Analysis

“…There were 10, 7, 8, 12, and 15 studies regarding rs266729 (5024 cases and 5545 controls) (Kaklamani et al, 2008a(Kaklamani et al, , 2008bPechlivanis et al, 2009;Beebe-Dimmer et al, 2010;Cui et al, 2011;He et al, 2011;Liu et al, 2011), rs822395 (2690 cases and 3265 controls) (Kaklamani et al, 2008a(Kaklamani et al, , 2008bBeebeDimmer et al, 2010;He et al, 2011), rs822396 (3611 cases and 4176 controls) (Kaklamani et al, 2008a(Kaklamani et al, , 2008bCarvajal-Carmona et al, 2009;Beebe-Dimmer et al, 2010;He et al, 2011), rs2241766 (4936 cases and 5452 controls) (Kaklamani et al, 2008a(Kaklamani et al, , 2008b (Table 1). Most studies were in accordance with HWE except for six, which were considered with caution (Kaklamani et al, 2008a(Kaklamani et al, , 2008bCui et al, 2011).…”

“…Partida-Perez et al, 2010;He et al, 2011;Liu et al, 2011;Keku et al, 2012;Tsilidis et al, 2009;Wang et al, 2009), respectively…”

Galectin‑3 rs4652 A>C polymorphism is associated with the risk of gastric carcinoma and P‑glycoprotein expression level

“…Gastric cancer rates are typically twice as high in males as in females, and China has one of highest incidence rates (1). Cancer is a complex disease that results from interactions between multiple genetic and environmental factors (2,3). Even between individuals with similar environmental risk factors, including Helicobacter pylori infection (4,5), smoking (6) and obesity (7), not all individuals will develop gastric carcinoma (GC).…”