Association of the C677T polymorphism in the MTHFR gene with breast and/orovarian cancer risk in Jewish women

The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with reduced enzyme activity, hyperhomocysteinaemia and incre ased risk for atherosclerosis in homozygotes. We examined the frequency of this mutation and its association with disease pattern in 491 Jewish women with either sporadic (n = 355; 72%) or hereditary (n = 136; 28%) breast and /or ovarian cancer and in 69 asymptomatic BRCA1/2 mutation carriers, genoty ped for the three predominant Jewish founder BRCA1/2 mutations (185delAG, 5 382insC and 6174delT). 677T homozygotes were equally distributed among wome n with sporadic breast and/or ovarian cancer (71/355; 20.0%) and among BRA1 /2 mutation carriers (43/205; 21.0%) (P = non-significant). 677T homozygote s were equally distributed among women diagnosed with breast cancer prior t o (22/122; 18.0%) and after 42 years of age (42/243; 17.3%). Among BRCA1/2 carriers, the rate of 677T homozygotes in manifesting cancer (32/136; 23.5% ) and asymptomatic individuals (11/69; 15.9%) was not significantly differe nt. The rate of 677T homozygotes (24/72; 33.3%) was higher (P = 0.0026) amo ng women with bilateral breast cancer and those with both breast and ovaria n carcinoma than among those with unilateral breast cancer (64/365; 17.5%). Differences in morbidity (one versus multiple breast/ovarian tumours) are mainly attributed to 677T homozygosity and partly to BRCA1/2 mutations. Con firmation of these data, namely, that the 677T allele is significantly more common in cases of bilateral breast cancer or combined breast and ovarian cancer would have important clinical implications. (C) 2000 Elsevier Scienc e Ltd. All rights reserved.