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Breast cancer susceptibility genes in estrogen metabolizing pathway in a southern Indian population
Andrea Mary Francisa, , Ramya R.b, Nalini Ganesanc, Kumarasamy P.d, Solomon F.D. Paula, Munirajan A.K.e, Divya M.a a Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, India b Department of General Surgery, Sri Ramachandra Institute of Higher Education and Research, India c Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, India d Madras Veterinary College, Tanuvas, Madhavaram milk colony, Chennai 600051, India e Department of Genetics, University of Madras, India
The most common cancer in women is breast cancer, and it poses serious health issues in women, leading to increased mortality rates. Estrogen and its metabolites have been established as risk factors for breast cancer. Determining the role of genetic variants having functional involvement in regulating the estrogen concentration and detoxifying the toxic estrogen metabolites through estrogen hydroxylation by CYP1A1, CYP1B1, and ca-techol estrogen inactivation by SULT1A1 may reveal crucial information on the identification of genetic bio-markers for breast cancer susceptibility, thus paving the way for monitoring, early detection, and personalized treatment. In the present study, 200 breast cancer and 200 control samples were analyzed with regard to genotypes for the polymorphism rs4646903, rs1048943, rs1056836, and rs9282861 found in the genes CYP1A1, CYP1B1, and SULT1A1, respectively, by real-time polymerase chain reaction. The study revealed positive as-sociation of CYP1A1 rs4646903 T to C polymorphism with breast cancer risk. A significant increase of TC and CC alleles of the gene CYP1A1 m1(T/C) genotype rs4646903 was found in patients in comparison with controls (OR = 1.68; 95% CI, 1.13–2.51; p: 0.009). A significant increase of GA and AA alleles of the SULT1A1 rs9282861 genotype was found in patients in comparison with controls (OR = 1.86; 95% CI, 1.21–2.86; p: 0.004). SULT1A1 Arg213His was found to contribute an elevated risk of breast cancer. There was no strong and significant linkage disequilibrium between these polymorphisms. CYP1A1 and SULT1A1 were found to be associated with pre-menopausal breast cancer cases and high tumor grade. Stratified analysis of the subjects based on receptor status revealed an association between SULT1A1 polymorphism and ER-positive breast cancer cases. The in silico analysis revealed structural variation in SULT1A1 gene with respect to rs9282861 polymorphism. The poly-morphisms rs9282861 of SULT1A1 and rs4646903 of CYP1A1 were found to be associated with breast cancer risk in southern Indian population.