Dataset Information

Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.

ABSTRACT:

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.

SUBMITTER: Li Q

PROVIDER: S-EPMC3734314 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.

Li Qiaoxin Q Gu Chengyuan C Zhu Yao Y Wang Mengyun M Yang Yajun Y Wang Jiucun J Jin Li L Zhu Mei-Ling ML Shi Ting-Yan TY He Jing J Zhou Xiaoyan X Ye Ding-wei DW Wei Qingyi Q

PloS one 20130805 8

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped s ...[more]

PMID: 23940798

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Project description:BACKGROUND: B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China. METHODS: We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes. RESULTS: Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status. CONCLUSION: These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.

Dataset Information

Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.

Background

Methodology/principal findings

Conclusions/significances

Publications

Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.

Similar Datasets

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