BACKGROUND: A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk. METHODS: We conducted a nested case-control study within a phase III prevention trial of tamoxifen. After a median follow-up of 81.2 months, 79 of the 5,408 hysterectomised women aged 35-70 years, who had received either tamoxifen 20 mg/day or placebo for 5 years, developed breast cancer. A total of 46 breast cancer cases and 80 unaffected controls matched to treatment allocation, years from randomization (+/-2 years) and age at randomization (+/-5 years), underwent genotyping for MTHFR C677T polymorphism using real time PCR. RESULTS: The MTHFR 677 genotype frequencies for CC, CT, TT in breast cancer cases were 30%, 44% and 26%, respectively, and 35%, 51%, 14% in controls. We observed a borderline significant odds ratio of 2.51 (95% CI, 0.96-6.55) of breast cancer in subjects with 677TT genotype, with no further association after stratifying for age and treatment group. A meta-analysis of 18 studies, including our own, showed an increased risk of breast cancer in premenopausal women with 677TT genotype, with an odds ratio of 1.42 (95% CI, 1.02-1.98). CONCLUSIONS: Our study lends support to a positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk. Additional studies are warranted to provide further insight into the role of folate metabolism deficiency and breast cancer.
BACKGROUND: A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk. METHODS: We conducted a nested case-control study within a phase III prevention trial of tamoxifen. After a median follow-up of 81.2 months, 79 of the 5,408 hysterectomised women aged 35-70 years, who had received either tamoxifen 20 mg/day or placebo for 5 years, developed breast cancer. A total of 46 breast cancer cases and 80 unaffected controls matched to treatment allocation, years from randomization (+/-2 years) and age at randomization (+/-5 years), underwent genotyping for MTHFRC677T polymorphism using real time PCR. RESULTS: The MTHFR 677 genotype frequencies for CC, CT, TT in breast cancer cases were 30%, 44% and 26%, respectively, and 35%, 51%, 14% in controls. We observed a borderline significant odds ratio of 2.51 (95% CI, 0.96-6.55) of breast cancer in subjects with 677TT genotype, with no further association after stratifying for age and treatment group. A meta-analysis of 18 studies, including our own, showed an increased risk of breast cancer in premenopausal women with 677TT genotype, with an odds ratio of 1.42 (95% CI, 1.02-1.98). CONCLUSIONS: Our study lends support to a positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk. Additional studies are warranted to provide further insight into the role of folate metabolism deficiency and breast cancer.
Authors: Rita de Cássia Carvalho Barbosa; Débora Costa Menezes; Thiago Fernando Vasconcelos Freire; Diogo Campos Sales; Victor Hugo Medeiros Alencar; Silvia Helena Barem Rabenhorst Journal: Mol Biol Rep Date: 2011-12-02 Impact factor: 2.316
Authors: Maria G Kakkoura; Christiana A Demetriou; Maria A Loizidou; Giorgos Loucaides; Ioanna Neophytou; Yiola Marcou; Andreas Hadjisavvas; Kyriacos Kyriacou Journal: Genes Nutr Date: 2015-01-21 Impact factor: 5.523
Authors: Kathryn L Terry; Shelley S Tworoger; Ellen L Goode; Margaret A Gates; Linda Titus-Ernstoff; Linda E Kelemen; Thomas A Sellers; Susan E Hankinson; Daniel W Cramer Journal: Gynecol Oncol Date: 2010-11 Impact factor: 5.482
Authors: Maki Inoue; Kim Robien; Renwei Wang; David J Van Den Berg; Woon-Puay Koh; Mimi C Yu Journal: Carcinogenesis Date: 2008-07-31 Impact factor: 4.944
Authors: Valli De Re; R Cannizzaro; V Canzonieri; E Cecchin; L Caggiari; E De Mattia; C Pratesi; P De Paoli; G Toffoli Journal: Tumour Biol Date: 2009-12-18