MODELO MULTIGÉNICO DE IDENTIFICACIÓN DE MUJERES DE ALTO RIESGO A DESARROLLAR CÁNCER DE MAMA POR MEDIO DEL ANÁLISIS POLIMORFICO DE COMPT, CYP17, CYP1A1, CYP19 Y RECEPTOR DE ESTRÓGENO

Abstract

Background. In Mexico, between women with cancer, the breast cancer is in first place like the cause of death. 65% of this women belong to the productive group between 35 to 64 years of age. Furthermore, the number of women below 40 years old affected with this kind of cancer is increased during the last five years. The breast cancer represent an important problem in public health, that is the reason because an urgent need to have a preventive alternative methods and secreening. The present proposal analyze five genes polymorphism, related to the estrogen carcinogenesis (COMPT, CYP17, CYP1A1, CYP19 and estrogen receptor), and their breast cancer association in Mexican women. Objective. To develop an identification of high risk women by a multigenetic model for breast cancer. Methods. We develop a cases and controls clinical study, where we select 100 breast cancer mexican women and 100 negative controls. We obtain DNA from peripheral blood for genotyping COMT, CYP17, CYP1A1 and estrogen receptor by PCR-RFLP, and by electrophoresis to CYP19. Genotype frequencies were estimated for all participants in the study. The association between genotypes and breast cancer risk was measured using a logistic regression likewise method to obtain the Odds Ratio (OR) and its corresponding 95% Confidence Intervals (95% CI) and adjusted for age. “p” values for chi-squared or Fisher exact tests were also calculated. The statistic programs utilized was SPSS versión 14 y Epi-Info 3.5.1. Results. The epidemiological factors independent analysis never show any breast cancer significant association. The results showed a high risk of breast cancer in women carrying the CYP1A1 (3801 T>C) m2/m2 genotype (OR=2.52; 95%CI=1.04-6.08). This risk was higher in postmenopausal women (OR=3.38; 95%CI=1.05-10.87). No association between COMT 1947 G>A CYP1A1m2, CYP17, ER and breast cancer was found. Finally, we show gene CYP19 genotype A21/A2 as a high risk to develop breast cancer (OR = 2.03; 95%CI= 0.96-4.26). Conclusions. This study suggests that the CYP1A1 (3801 T>C) m2/m2 genotype may contribute to breast cancer susceptibility in Mexican women. With this data we proposed a risk model ready for validation.