Abstrak: Adenomatous polyposis coli gene (APC) polymorphisms may influence the risk for colorectal neoplasia. However, results thus far have been inconclusive. We performed a systematic literature search of the Medline, Embase, Cochrane Collaboration, and HuGE databases and reviewed the references of pertinent articles through May 2012. Odds ratios with 95% confidence intervals were used to estimate the association between 3 APC polymorphisms (D1822V, E1317Q, and I1307K) and colorectal neoplasia. In total, 40 studies from 1997 to 2010 were included in this meta-analysis, and individuals with the D1822V variant homozygote VV genotype had a slight decrease in the risk for colorectal neoplasia compared with the wild-type homozygote DD genotype (pooled odds ratio = 0.87, 95% confidence interval: 0.77, 0.99). There was a small association between the APC E1317Q polymorphism and a risk for colorectal neoplasia (variant vs. wild-type: pooled odds ratio = 1.41, 95% confidence interval: 1.14, 1.76), particularly for colorectal adenomas (variant vs. wild-type: odds ratio = 2.89, 95% confidence interval: 1.83, 4.56). Compared with those who carried the wild-type I1307K, Ashkenazi Jews who carried the I1307K variant were at a significantly increased risk for colorectal neoplasia, with a pooled odds ratio of 2.17 (95% confidence interval: 1.64, 2.86). Our study suggests that APC is a candidate gene for colorectal neoplasia susceptibility.

Abstrak: A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 × 10(-67), P = 3.98 × 10(-5), P = 6.97 × 10(-9), and P = 5.33 × 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 × 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 × 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 × 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout.