Breast cancer risk and methylenetetrahydrofolate reductase polymorphism.
OBJECTIVE
Methylenetetrahydrofolate reductase (MTHFR), a polymorphic enzyme involved in folate metabolism, plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. Because breast-cell division occurs in women with active ovulatory cycles, polymorphisms in the MTHFR gene could be a risk factor for breast cancer.


METHODS
We genotyped 352 clinic-based study subjects for MTHFR, 105 subjects with breast cancer and 247 with benign breast disease, histopathologically classified as high-risk or low-risk for breast cancer. Questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses.


RESULTS
Premenopausal women with the MTHFR polymorphism had a threefold increased breast cancer risk (OR = 2.8; 95%CI: 1.02-7.51) compared to the clinic-based controls with benign breast disease. Results were similar using either low- or high-risk controls. However, risk for postmenopausal women was not elevated (OR = 0.8; 95%CI 0.4-1.4). No significant interaction between genotype and smoking or alcohol was found, but polymorphic MTHFR decreased the likelihood of drinking alcohol (OR = 0.5; 95%CI 0.3-0.9).


CONCLUSIONS
These data suggest that polymorphic MTHFR increases risk of premenopausal, but not postmenopausal, breast cancer. These findings should be explored with a larger sample size in order to analyze gene-environment interactions between MTHFR and folate. Once the intricate relationship between diet and breast cancer has been elucidated, new cancer control initiatives can be considered such as folate chemoprevention trials in high-risk individuals.
Semenza
Jan C
JC
School of Community Health, College of Urban and Public Affairs, Portland State University, Portland, OR, USA.
Delfino
Ralph J
RJ
Ziogas
Argyrios
A
Anton-Culver
Hoda
H
D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D006801:Humans; D008593:Menopause; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D011795:Surveys and Questionnaires
D017931:DNA Primers; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)