Publication: Role of genetic variations of parp1 polymorphisms on triple negative breast cancer (TNBC) susceptibility risk
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Date
2022
Authors
Zamri, Durar Aqilah
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Abstract
Background: Breast cancer is the most common cancer in females worldwide and the second most common cause of cancer deaths. Triple negative breast cancer (TNBC) has the most aggressive phenotype and worst prognosis compared to other breast cancer subtypes. Poly(ADP-Ribose)Polymerase1 (PARP1) is a nuclear protein, that plays a role in deoxyribonucleic acid (DNA) damage repair by acting as sensor for DNA strand breaks. Inter-individual genetic variations such as single nucleotide polymorphisms (SNPs) of PARP1 Val762Ala (rs1136410 T>C) and Ala284Ala (rs1805414 T>C) may reduce the PARP1 activity in repairing DNA damage and thus may increase the cancer risk predisposition. Since there is paucity of information on the frequency of PARP1 rs1136410 T>C and rs1805414 T>C polymorphisms in TNBC patients, and limited reports available on these polymorphisms on TNBC susceptibility risk, the present study is designed to investigate the impact of PARP1 rs1136410 T>C and rs1805414 T>C polymorphisms in modulating TNBC susceptibility risk. Methods: Blood sample of 70 histopathologically confirmed TNBC patients and 70 healthy control individuals were collected, and DNA was extracted. The genotyping of PARP1 rs1136410 T>C and rs1805414 polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-polymerase chain reaction (AS-PCR) technique, respectively. Next, the genotype patterns were categorized into homozygous wild-type, heterozygous and homozygous variant. The genotype and allele frequencies of both PARP1 polymorphisms were calculated and compared between TNBC patients and healthy individual group using chi-square test. Next, logistic regression analysis deriving Odds Ratio (OR) with 95% confidence interval (CI) was performed to evaluate the TNBC patients’ susceptibility risk. Results: The homozygous variant (CC) genotype of PARP1 rs1136410 polymorphism and heterozygous (TC) genotype of PARP1 rs1805414 showed a higher TNBC susceptibility risk with OR: 1.190, 95% CI: 0.300-4.721 and OR: 1.103, 95% CI: 0.402-3.031. In addition, heterozygous (TC) genotype of PARP1 rs1136410 was found to be significantly associated with lower risk of recurrence among TNBC patients with OR: 0.105, 95% CI: 0.029-0.374, p=0.001. Conclusion: Our results showed the lack of association of PARP1 rs1136410 T>C and rs1805414 T>C polymorphisms in modulating TNBC susceptibility risk. However, the present study observed that PARP1 rs1136410 (TC) genotype was found to be significantly associated with lower risk of disease recurrence among TNBC patients. The lack of association could be due to low sample size of study subjects which interfered the power of the study and influence the low frequency of variant allele in TNBC patients. The study needs to be extended to larger number of sample size which can increase the power of the study and needs to explore the polymorphic genotype combinations of PARP1
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Keywords
Triple Negative Breast Cancer , PARP1 gene polymorphism