Breast cancer risk associated with multigenotypic polymorphisms in folate-metabolizing genes: a nested case-control study in Taiwan.
OBJECTIVE
The purpose of this study was to test the hypothesis that multigenotypic polymorphisms in the folate metabolic pathway, which may result in genomic instability and inbalance of estrogen metabolism, were associated with breast cancer risk.


METHODS
A population-based nested case-control study of 109 cases with pathologically confirmed invasive breast cancer and 421 cancer-free controls was conducted in Taiwan between 1992 and 2001. The polymorphisms in serine hydroxymethyltransferase (SHMT1 C1420T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T), and methionine synthase (MS A2756G) genes were examined using polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
There was a trend toward an increased risk of breast cancer in women harboring a greater number of putative high-risk genotypes of these genes. Furthermore, the cancer risk associated with having at least one putative high-risk genotype was more significant in women having been exposed to estrogen for a longer period before first birth.


CONCLUSIONS
The present study indicates the significance of multiple low-penetrance alleles of functionally-related folate-metabolizing genes interactive with an estrogenic environment in breast tumorigenesis.
Yu
Cheng-Ping
CP
Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, ROC.
Wu
Mei-Hsuan
MH
Chou
Yu-Ching
YC
Yang
Tsan
T
You
San-Lin
SL
Chen
Chien-Jen
CJ
Sun
Chien-An
CA
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D019683:Penetrance; D011110:Polymorphism, Genetic; D013624:Taiwan
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human