The MTHFR C677T polymorphism, estrogen exposure and breast cancer risk: a nested case-control study in Taiwan.
BACKGROUND
We evaluated the effects of the MTHFR C677T polymorphism and its interaction with estrogen exposure on breast cancer risk in a nested case-control study conducted in Taiwan.


METHODS
A total of 88 histologically confirmed breast cancer cases and 344 cancer-free controls were recruited between July 1992 and December 2000. The MTHFR C677T genotype was determined by a PCR-RFLP-based assay. All subjects completed in-person interviews.


RESULTS
There was a significant trend of breast cancer in relation to prolonged exposure to estrogens prior to the first full-term pregnancy (FFTP) (p for trend = 0.0015). In contrast, there was no statistically significant association between the risk of breast cancer and the MTHFR C677T genotype. However, a significantly elevated risk of breast cancer predisposed by the MTHFR 677T variant genotype (CT and TT) was observed in women with prolonged exposure to estrogens prior to FFTP (adjusted OR = 4.98, 95% CI = 2.00-12.43).


CONCLUSIONS
The results of this study suggest that the MTHFR 677T variant genotype per se may have no overall association with breast cancer risk, but a sizable association could be observed in the presence of relevant environmental exposure.
Lin
Wei-Yu
WY
School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chou
Yu-Ching
YC
Wu
Mei-Hsuan
MH
Huang
Han-Bin
HB
Jeng
Yi-Lin
YL
Wu
Cho-Chieh
CC
Yu
Cheng-Pung
CP
Yu
Jyh-Cherng
JC
You
San-Lin
SL
Chu
Tang-Yuan
TY
Chen
Chien-Jen
CJ
Sun
Chien-An
CA
D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004967:Estrogens / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008572:Menarche; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013624:Taiwan / Q000453:epidemiology
D004967:Estrogens; D042965:Methylenetetrahydrofolate Reductase (NADPH2)