MTHFR c.677C>T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai.
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.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Jun-Long
JL
Wu
The State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics &Development, School of Life Sciences, Fudan University, Shanghai 200433, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Shu-Xian
SX
Zhou
The State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics &Development, School of Life Sciences, Fudan University, Shanghai 200433, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Rui
R
Zhao
The State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics &Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
Xuan
X
Zhang
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Kun
K
Chang
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cheng-Yuan
CY
Gu
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Hua-Lei
HL
Gan
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Bo
B
Dai
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Yao
Y
Zhu
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Hai-Liang
HL
Zhang
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Guo-Hai
GH
Shi
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Yuan-Yuan
YY
Qu
The State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics &Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
Jian-Yuan
JY
Zhao
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Ding-Wei
DW
Ye
D000368:Aged; D044466:Asian People; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002681:China / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
D009363:Neoplasm Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)