Estrogen Receptor Alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa

AbstractBackground: Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association ofESR1(rs2234693 and rs2046210) with breast cancer risk was investigated in Khyber Pakhtunkhwa patients. Methods: A total of 222 women including 162 breast cancer patients and 60 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR. Results: Our results revealed thatESR1-rs2234693 risk allele (C) (P = 0.2, OR = 1.34, CI = 0.7 to 2.3) and containing genotypes CC (P = 0.61, OR = 1.50, CI = 0.31 to 7.30) and TC (P = 0.7, OR = 1.11, CI = 0.59 to 2.09) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P = 0.0006, OR = 7.50, CI = 0.77 to 2.33) and corresponding genotypes GA (P = 0.003, OR = 2.44, CI = 1.33 to 4.47) and AA (P = 0.3, OR = 3.15, CI = 1.06 to 9.38) were significantly associated with higher risk of breast cancer. Moreover,ESR1-rs2234693 was significantly (P < 0.05) associated with family history, stages, PR status, ER status and luminal B. TheESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P > 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A. Conclusion: It is concluded thatESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation ofESR1polymorphism,ESR1existing and other SNPs need to be checked in diverse data sets.