Prevalence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Risk of Breast Cancer in Mexican Women: An Interim Report of a Case-Control Study.

Abstract

Abstract Background: Among other causes, Breast Cancer (BC) appears as a result of genetic and epigenetic changes. Modifications in important pathways, such as the reactions that provide essential cofactors for synthesis of S-adenosylmethionine (one-carbon metabolism), and those involved in DNA synthesis and methylation could be linked to the development of this disease. Research has been conducted about whether MTHFR polymorphisms are related to the development of breast cancer in at least 10 different races, with different outcomes. Two of the most frequently studied MTHFR polymorphisms are C677T and A1298C, and their frequency is unknown among Mexican women. Our objective was to determine the frequency of these two polymorphisms and to ascertain weather their presence increases the risk of developing BC in our population.Materials and methods: 37 blood samples from histopatologically confirmed breast cancer patients were collected from hospitals in Monterrey, Uruapan and Villahermosa, all in Mexico. 115 healthy control samples were obtained from the same cities, and were matched for age in 5-year interval-groups. Cases and controls were third generation Mexican and older than 18 years. Genotyping of every sample was performed by PCR and restriction with enzymes.Results: The C677T Polymorphism was found in 28 cases (75.67%), whereas 76/115 controls (66.08%) showed the polymorphic allele. Case-controls analysis was adjusted to the confounding variable age group, an odds ratio of 1.58 (IC 95% de 0.66 – 3.82) was obtained. We did not find a significant relationship between the presence of the C677T polymorphism and the presence of breast cancer. The A1298C Polymorphism was found in 19/37 cases (51.35%), while only 32/115 (27.82%) of the control samples contained the allele. The odds ratio adjusted for the same confounding variable was 2.72 (IC 95%: 1.26 – 5.87). These results suggest a significant association between the presence of the polymorphism and BC.Discussion: Despite the exhaustive research that has been conducted regarding MTHFR polymorphisms C677T and A1298C, their association to the risk of breast cancer remains unclear. Some research groups even suggest that the presence of the polymorphisms, either individually or combined, confers certain protection against the disease. Up until now there were no data in Mexican population. Differences in the results of different works probably lie in the nature of the populations analyzed and the experimental design. We believe that a bigger sample size will allow us to determine if A1298C polymorphism is indeed, a risk factor for BC in Mexican women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3064.