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Background: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. Methodology/Principal Findings: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. Conclusions/Significances: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies. [ABSTRACT FROM AUTHOR]

Purpose: Transforming growth factor (TGF) -β1 signaling is involved in cancer-cell metastasis. We investigated whether single nucleotide polymorphisms (SNPs) at TGFβ1 were associated with overall survival (OS) and distant metastasis-free survival (DMFS) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy, with or without chemotherapy. Methods: We genotyped TGFβ1 SNPs at rs1800469 (C–509T), rs1800471 (G915C), and rs1982073 (T+29C) by polymerase chain reaction-restriction fragment length polymorphism in blood samples from 205 NSCLC patients who had had definitive radiotherapy at one institution in November 1998–January 2005. We also tested whether the TGF-β1 rs1982073 (T+29C) SNP affected the migration and invasion of A549 and PC9 lung cancer cells. Results: Median follow-up time for all patients was 17 months (range, 1–97 months; 39 months for patients alive at the time of analysis). Multivariate analysis showed that the TGFβ1 rs1800469 CT/CC genotype was associated with poor OS (hazard ratio [HR] = 1.463 [95% confidence interval {CI} = 1.012–2.114], P = 0.043) and shorter DMFS (HR = 1.601 [95% CI = 1.042–2.459], P = 0.032) and that the TGFβ1 rs1982073 CT/CC genotype predicted poor DMFS (HR = 1.589 [95% CI = 1.009–2.502], P = 0.046) and poor brain MFS (HR = 2.567 [95% CI = 1.155–5.702], P = 0.021) after adjustment for age, sex, race, performance status, smoking status, tumor histology and volume, stage, receipt of concurrent radiochemotherapy, number of chemotherapy cycles, and radiation dose. Transfection with TGFβ1+29C (vs. +29T) stimulated the migration and invasion of A549 and PC9 cells, suggesting that TGFβ1+29C may be linked with increased metastatic potential. Conclusions: TGFβ1 genotypes at rs1800469 and rs1982073 could be useful for predicting DMFS among patients with NSCLC treated with definitive radiation therapy. These findings require validation in larger prospective trials and thorough mechanistic studies. [ABSTRACT FROM AUTHOR]

Background: TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3′UTR of TNFAIP2 and gastric cancer risk in a US population. Methods: We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T>C, rs710100 G>A, rs1052912 G>A and rs1052823 G>T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk. Results: The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09–3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric cancer. Conclusions: Our data suggested that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies. [ABSTRACT FROM AUTHOR]

Background: Both microRNAs and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, microRNAs affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that microRNA polymorphisms modify the association between HPV16 seropositivity and OSCC risk. Methods: Four single-nucleotide polymorphisms in microRNAs were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models. Results: Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both miR146 rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9–1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8–5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3–9.4). Similar results were found for miR149 rs2292832, miR196 rs11614913, and miR499 rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers. Conclusions: Our results indicate that microRNA polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]