Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer.

BACKGROUND: Metabolic 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 FINDINGS: To 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 to 2.54-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/SIGNIFICANCE: Our 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.

An integrated meta-analysis of two variants in HOXA1/HOXB1 and their effect on the risk of autism spectrum disorders.

BACKGROUND: HOXA1 and HOXB1 have been strongly posed as candidate genes for autism spectrum disorders (ASD) given their important role in the development of hindbrain. The A218G (rs10951154) in HOXA1 and the insertion variant in HOXB1 (nINS/INS, rs72338773) were of special interest for ASD but with inconclusive results. Thus, we conducted a meta-analysis integrating case-control and transmission/disequilibrium test (TDT) studies to clearly discern the effect of these two variants in ASD. METHODS AND FINDINGS: Multiple electronic databases were searched to identify studies assessing the A218G and/or nINS/INS variant in ASD. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. A total of 10 and 7 reports were found to be eligible for meta-analyses of A218G and nINS/INS variant, respectively. In overall meta-analysis, the pooled OR for the 218G allele and the INS allele was 0.97 (95% CI = 0.76-1.25, P(heterogeneity) = 0.029) and 1.14 (95% CI = 0.97-1.33, P(heterogeneity) = 0.269), respectively. No significant association was also identified between these two variants and ASD risk in stratified analysis. Further, cumulative meta-analysis in chronologic order showed the inclination toward null-significant association for both variants with continual adding studies. Additionally, although the between-study heterogeneity regarding the A218G is not explained by study design, ethnicity, and sample size, the sensitive analysis indicated the stability of the result. CONCLUSIONS: This meta-analysis suggests the HOXA1 A218G and HOXB1 nINS/INS variants may not contribute significantly to ASD risk.