Genetic variants of EGFR (142285G>A) and ESR1 (2014G>A) gene polymorphisms and risk of breast cancer

Breast cancer is one of the most common cancers in women worldwide. The estrogen receptor alpha (ESR1) and epidermal growth factor receptor (EGFR) have been known to play a vital role in development and progression of breast cancer. The aim of the present study was to determine the relationship, if any, between genetic polymorphism in (ESR1) 2014G > A (T594T) and (EGFR) 142285G > A (R521K) with risk of breast cancer and the prognosis in a heterogeneous North Indian population that is known for its diverse ethnicity. A case-control study in a total of 300 individuals comprising of 150 breast cancer patients and 150 normal controls was performed. PCR-RFLP was employed for genotyping. The G/A heterozygous genotype EGFR R521K, was slightly higher in cases (56.7 %) than in controls (48.3 %) (P = 0.20). The results indicated that EGFR polymorphism does not show any significant association with breast cancer in this population. On the other hand, the mutant A/A genotype ESR1 codon 594, showed a 6.4-folds risk for breast cancer and this association was highly significant (P = 0.00) as compared to wild GG genotype, the heterozygous G/A genotype also showed a significant association with disease (P = 0.00, OR = 2.03). In addition, the frequency of A allele was also higher in cases (36 %) than in controls (19 %) and a highly significant difference was observed with wild G allele (63.3 % in cases and 6.6 % in controls). This clearly indicates that there appears to be an influence of ESR1 codon 594 genotypes on genetic susceptibility to breast cancer. Further a significantly higher risk was observed in individuals who had diabetes {OR = 3.04 (1.68-5.50), P = 0.00} and females with ESR polymorphism in pre-menopause patients that had undergone menopause above the age of 50 years {OR = 3.58 (1.86-6.90), P < 0.05}. The different ethnic backgrounds and geographical locations have complimented the present genotypic analysis and have highlighted the influence of ethnicity, race and geographic location in genetic predisposition to breast cancer.