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Estrogen receptor alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in pashtun population of Khyber Pakhtunkhwa

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Abstract

Background:

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 of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in patients of Khyber Pakhtunkhwa.

Methods:

A total of 312 females including 162 breast cancer patients and 150 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR.

Results:

Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.21, OR = 1.27, CI = 0.87 to 1.87) and containing genotypes CC (P = 0.68, OR = 1.24, CI = 0.42 to 3.68) and TC (P = 0.23, OR = 1.32, CI = 0.83 to 2.13) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P < 0.0001, OR = 2.42, CI = 1.74 to 3.38) and corresponding genotypes GA (P = 0.0001, OR = 2.55, CI = 1.62 to 4.03) and AA (P = 0.02, OR = 2.20, CI = 1.12 to 4.34) 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. The ESR1-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 that ESR1-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 of ESR1 polymorphism, ESR1 existing and other SNPs need to be investigated in diverse data sets.

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Acknowledgements

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Funding

There is no funding received for this work, the authors have contributed their self for experimental cost.

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Authors and Affiliations

  1. Institute of Biotechnology and Genetic Engineering (Health Division), The University of Agriculture Peshawar, Peshawar, Pakistan

    Savera Shahzad, Najeeb Ullah Khan, Wafa Sombal, Rizwan Ullah Shah, Aqib Iqbal & Iqbal Munir

  2. Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, Pakistan

    Aakif Ullah Khan

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  1. Savera Shahzad
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  2. Najeeb Ullah Khan
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Contributions

SS collect the data, did the experiments and write the article. NUK and AQ designed and supervised the study. WS, RUS, AUK and IM facilitated the study, support the patient’s enrolment and review the article.

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Correspondence to Najeeb Ullah Khan.

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Ethical approval was taken from the institute of Biotechnology and Genetic Engineering, and written consent was taken from all the participants after explaining the aim and objective of the study.

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Shahzad, S., Khan, N.U., Sombal, W. et al. Estrogen receptor alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in pashtun population of Khyber Pakhtunkhwa. Mol Biol Rep 50, 2445–2451 (2023). https://doi.org/10.1007/s11033-022-08198-z

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