Genetics risk assessment of PALB2 polymorphism (rs249954 and rs152451) with breast cancer susceptibility among the Pashtun population of Khyber Pakhtunkhwa, Pakistan

Abstract

The partner and localizer of BRCA2 (PALB2) gene play an important role in DNA damage repair and control of many biological processes. The occurrence of specific genetic variations, known as single nucleotide polymorphisms (SNPs), in the PALB2 gene has been identified as a factor contributing to an increased susceptibility to breast cancer. The SNPs in PALB2 (rs249954 and rs152451) are identified and associated with breast cancer risk, however its role remains unknown in the Pashtun ethnic group, making it necessary to explore in this population. This case-controls study included 100 breast cancer patients and 100 healthy controls. The SNPs genotyping was performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR). The statistical analysis revealed a significant association between the risk allele of rs249954 and an elevated breast cancer risk (P = 0.0001), while rs152451 did not exhibit a significant association (P = 0.07). Heterozygous genotype of rs249954 was linked to increased breast cancer risk (P = 0.0001), whereas rs152451 did not show a significant association (P = 0.08). Mutant genotypes of both the SNPs correlated positively with breast cancer risk (P = 0.002, P = 0.042). Additionally, rs249954 exhibited significant association with Nodal status (P=0.01), Metastasis (P=0.01) and PR status (P=0.01). While PALB2 (rs142451) failed to exhibit significant association with any of the selected demographic and clinical parameters. In conclusion, the risk allele and both the heterozygous and homozygous genotypes of rs249954 were associated with an increased risk of breast cancer, whereas only homozygous mutant genotype of rs152451 exhibited significant association. However, further studies with larger datasets and comprehensive genomic analysis are necessary to validate these findings and explore associations with other relevant SNPs.