1. MTHFR c.677C>T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai
- Author
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Jun Long Wu, Hua Lei Gan, Guo Hai Shi, Yao Zhu, Dingwei Ye, Yuan-Yuan Qu, Shu Xian Zhou, Xuan Zhang, Bo Dai, Kun Chang, Jian-Yuan Zhao, Rui Zhao, Hai Liang Zhang, and Cheng Yuan Gu
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,China ,Homocysteine ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Asian People ,Prostate ,Internal medicine ,Cell Line, Tumor ,Genotype ,medicine ,Humans ,Point Mutation ,Genetic Predisposition to Disease ,Allele ,Methylenetetrahydrofolate Reductase (NADPH2) ,Aged ,Cell Proliferation ,Multidisciplinary ,biology ,Cell growth ,business.industry ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,digestive system diseases ,Neoplasm Proteins ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Methylenetetrahydrofolate reductase ,biology.protein ,business - Abstract
Methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C variants were known to be associated with prostate cancer (PCa) risk with conflicting results, because of MTHFR and nutrient status interaction in the prostate development. In this large-scale, hospital-based, case-control study of 1817 PCa cases and 2026 cancer-free controls, we aimed to clarify the association between these two MTHFR variants and PCa risk in Shanghai and to explore the underlying molecular mechanisms. We found that both the heterozygous CT (adjusted OR = 0.78, 95% CI: 0.67–0.92) and the homozygous TT genotypes (adjusted OR = 0.68, 95% CI: 0.55–0.83) of c.677C>T were associated with a significantly decreased risk of PCa compared with homozygous wild-type CC genotype, respectively, using multivariate logistic regression. Furthermore, we confirmed that MTHFR c.677T allele was related to an increased serum homocysteine level in the Han Chinese population in Shanghai. In the cultured PCa cell lines, we observed that MTHFR c.677T could elevate the cellular homocysteine level and cause DNA damage, thus increasing cell apoptosis and finally inhibiting cell proliferation. In conclusion, MTHFR c.677T was a protective factor of PCa risk in ethnic Han Chinese males by inducing DNA damage and cell apoptosis.
- Published
- 2016