Genetic Polymorphism of GSTM1, GSTT1, GSTP1 Genes and Breast Cancer Risk in Rural Maharashtra: Insights from a Case- Control Study.

BACKGROUND

Breast cancer (BC) is a complex, multifactorial disease where genetic factors are one of the key determinants playing an important role in carcinogenesis process. The discrepancies in the reports all around the world in relation with the association of polymorphisms of glutathione S- transferase (GST) genes with BC risk encouraged us to assess the correlation of polymorphism in GST gene isoforms with BC susceptibility in the rural population of Maharashtra.

METHODS

The association of GSTM1 and GSTT1 gene polymorphisms with BC risk was studied by polymerase chain reaction (PCR) method using 400 clinically confirmed BC cases and equal number of healthy controls. The GSTP1 Ile/Val of exon 5 and Ala/Val of exon 6 polymorphism was determined by PCR followed by restriction fragment length polymorphism (PCR-RFLP). The logistic regression model was used to study the association of polymorphism with BC risk which was confirmed by Odds ratio (OR) with 95% confidence interval.

RESULTS

The frequency distribution of GSTT1 showed contributory increase of BC risk in association with null genotypes (OR = 2.45; 95%CI = 1.73-3.48, p<0.0001) where, GSTT1 null (-/-) genotypes increased risk of BC by 2.45 folds in the studied population. The results of genetic association analysis of GSTP1showed that heterozygous Ala/Val genotype of GSTP1 was associated with decreased risk of BC (OR=0.26, 95% CI: 0.18-0.35; p<0.0001, χ2 = 71.48) in the studied population.

CONCLUSION

Our results indicated that GSTT1 null genotype was significantly associated and GSTP1 heterozygous variant genotype was negatively associated with BC risk in women of rural Maharashtra.