Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls |
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| Authors: | Xiaowei Qi Xiangyu Ma Xinhua Yang Linjun Fan Yi Zhang Fan Zhang Li Chen Yan Zhou Jun Jiang |
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| Institution: | (1) Breast Disease Center, Southwest Hospital, Third Military Medical University, Gaotanyan Street 29, Chongqing, 400038, China;(2) Department of Epidemiology, Faculty of preventive medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, China; |
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| Abstract: | The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely
reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast
cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the
risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web
of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of
41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865
controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant
genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal
status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs.
C: OR = 1.041, 95% CI = 1.009–1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019–1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014–1.236);
in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121,
95% CI = 1.016–1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073–1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058–1.513) but not
in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found.
With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity-
and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play
a low penetrance role in the development of breast cancer. |
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