Null allele polymorphisms in the GSTT1 and GSTM1 genes in 705 women from a mammographic breast cancer screening program (NMPOA) in southern Brazil

Abstract

21091 Background: Several genetic polymorphisms in genes related with metabolism have been associated with breast cancer (BC) risk. Among these, the gluthatione-S-transferase M1 and T1 null genotypes have been associated with slightly increased BC risk in some populations. In Brazil, BC is a significant public health problem, due to its high incidence and mortality rates. In Porto Alegre, Brazil`s southernmost capital, a multidisciplinary BC Prevention Project - the Nucleo Mama Porto Alegre Cohort (NMPOA)- was started in 2004 and includes a mammographic screening program for women ages 40–69 years. Goal:Determine the allelic and genotypic frequencies of GSTM1 and GSTT1 null alleles in women undergoing annual mammographic screening and correlate its presence with mammography results and presence of additional BC risk factors at baseline and after 10 years. Methods: A sample of 705 women from the NMPOA BC screening program was consecutively enrolled from November/2005 until March/2006. Mammography results (BIRADS categories) and BC risk information (5-yr and vital estimates using the Gail model, family history of BC, body mass index) were obtained by chart review. Genotyping was performed by multiplex polymerase chain reaction (PCR). Results: Of the 705 patients studied, 145 (20.6%) and 314 (44.5%) had the GSTT1 and GSTM1 null alleles, respectively. Genotypically, 67 (9,5%) were null homozygous for both genes (GSTM1- and GSTT1- ); 78 (11,1%) were GSTT1- and non-null for GSTM1 (GSTT1- and GSTM1+); 247 (35%) were GSTT1+ and GSTM1- and 313(44,4%) were GSTM+ and GSTT+. There was a statistically significant association of the GSTT1+ allele with low-risk mammographic findings (category BIRADS 1; p<0,05). Conclusions: The genotypic and allelic frequencies of the GSTT1 and GSTM1 null alleles were not significantly different from those reported previously for other populations. The non-null GSTT1 allele was associated with lower category mammographic findings. Prospective clinical evaluation of the women followed in this program and correlation of genotype with clinical findings may elucidate additional risks associated with the presence of these polymorphisms. No significant financial relationships to disclose.