Abstrak: Preferential loss of heterozygosity at the rs1042522 locus of the tumor protein 53 gene (TP53) (Arg72Pro) is observed in several tumors. Genetic association studies in oncology often use tumor tissue rather than unaffected tissue for genotyping; in such cases, loss of heterozygosity at the TP53 locus could lead to differential misclassification and could bias estimates of association. We searched multiple databases (through March 8, 2011) for studies investigating the association of Arg72Pro with breast, lung, colorectal, ovarian, or endometrial cancer. Meta-analysis was performed with multilevel Bayesian models. Informative priors for the bias effect were derived from a meta-analysis of the same polymorphism in cervical cancer. Of 160 studies (68 breast, 42 lung, 26 colorectal, 16 ovarian, and 8 endometrial cancer), 22 used tumor tissue as the source of genotyping material for cases. Use of tumor tissue versus other sources of genotyping material was associated with an apparent protective effect of the proline allele (relative odds ratio = 0.78, 95% credible interval: 0.70, 0.88). The probability that use of tumor tissue induced bias was estimated to be higher than 99%. Use of tumor tissue as the source of genotyping material for cases is associated with significant bias in the estimate of the genetic effect in cancer genetic association studies.

Abstrak: We evaluated the associations of liver aminotransferases with risk of type 2 diabetes (T2D) in general populations by conducting a systematic review and meta-analysis of published prospective studies. Studies were identified in a literature search of PubMed, EMBASE, and Web of Science from 1950 through October 2012. Of the 2,729 studies reviewed, 17 studies involving 60,359 participants and 3,890 incident T2D events were included. All of the studies assessed associations between alanine aminotransferase (ALT) level and T2D, with heterogeneous findings (I(2) = 88%, 95% confidence interval (CI): 82, 92; P < 0.001). The pooled fully adjusted relative risk of T2D was 1.26 (95% CI: 1.14, 1.41) per 1-standard-deviation change in log baseline ALT level. This association became nonsignificant after trim-and-fill correction for publication bias. Nine studies evaluated associations between aspartate aminotransferase (AST) levels and T2D risk, with a corresponding relative risk of 1.02 (95% CI: 0.99, 1.04). The relative risk of T2D per 5-IU/L increase in ALT level was 1.16 (95% CI: 1.08, 1.25). Available data indicate moderate associations of ALT with risk of T2D events, which may be attributable to publication bias. There was no evidence for an increased risk of T2D with AST. Large prospective studies may still be needed to establish the magnitude and nature of these associations.

Abstrak: There are limited studies addressing whether proteinuria and estimated glomerular filtration rate (eGFR) are independently associated with cardiovascular disease in Asia. Using data from 7 prospective cohorts recruited between 1980 and 1994 in Japan, we assessed the influence of proteinuria (≥1+ on dipstick) and reduced eGFR on the risk of cardiovascular disease mortality in 39,405 participants (40-89 years) without kidney failure. During a 10.1-year follow-up, 1,927 subjects died from cardiovascular disease. Proteinuria was associated with a 1.75-fold (95% confidence interval (CI): 1.44, 2.11) increased risk of cardiovascular disease mortality after adjustment for potential confounding factors. Additionally, the multivariate-adjusted hazard ratio of cardiovascular disease mortality increased linearly with lower eGFR levels (P(trend) < 0.001): Subjects with eGFR of < 45 mL/minute/1.73 m² had a 2.22-fold (95% CI: 1.60, 3.07) greater risk of cardiovascular disease mortality than those with eGFR of ≥90 mL/minute/1.73 m^². Subjects with both proteinuria and eGFR of < 45 mL/minute/1.73 m² had a 4.05-fold (95% CI: 2.55, 6.43) higher risk of cardiovascular disease mortality compared with those with neither of these risk factors. There was no evidence of interaction in the relationship between proteinuria and lower eGFR (P(interaction) = 0.77). The present results suggest that proteinuria and lower eGFR are independent risk factors for cardiovascular disease mortality in the Japanese population.

Abstrak: Studies over 5 decades have examined ABO blood groups and risk of pancreatic cancer in Western, Asian, and other populations, though no systematic review has been published. We studied data from 908 pancreatic cancer cases and 1,067 population controls collected during December 2006-January 2011 in urban Shanghai, China, and reviewed the literature for all studies of this association. Random-effects meta-analysis provided summary odds ratio estimates according to blood group and by populations endemic versus nonendemic for cytotoxin-associated gene A (CagA)-positive Helicobacter pylori. In our Shanghai study, versus group O, only ABO group A was associated with risk (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.27, 2.03). In 24 pooled studies, group A showed increased risk in both CagA-nonendemic and -endemic populations (ORpooled = 1.40, 95% CI: 1.32, 1.49). In nonendemic populations, groups B and AB were also associated with higher risk (OR = 1.38, 95% CI: 1.16, 1.64; and OR = 1.52, 95% CI: 1.24, 1.85, respectively). However, in CagA-endemic populations, groups B and AB were not associated with risk (OR = 1.05, 95% CI: 0.92, 1.19; and OR = 1.13, 95% CI: 0.92, 1.38, respectively). These population differences were significant. One explanation for contrasts in associations of blood groups B and AB between CagA-endemic and -nonendemic populations could involve gastric epithelial expression of A versus B antigens on colonization behaviors of CagA-positive and CagA-negative H. pylori strains.

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.