Evaluation of CASP8 rs10931936 and rs1045485 Polymorphisms and haplotypes impact on the risk of Breast Cancer: A case-control study

Abstract Introduction Single nucleotide polymorphisms account for the majority of genetic predisposition to breast cancer in the general population. According to the lack of studies concerning the two common polymorphisms in CASP8 namely rs104548 and rs10931936 in Iranian population, we evaluated the association of these two polymorphisms and their haplotypes with breast cancer and molecular profile. Materials and Method Blood samples were collected from 287 breast cancer patients and 490 controls. Genotyping of rs1045485 and rs10931936 was conducted by ARMS and PCR-RFLP, respectively. PHASE was used to estimate the frequencies of haplotypes. Statistical analysis was performed using SPSS 16.0. Results While hormone receptors and the molecular profile did not indicate any significant association with different genotypes (p>0.05), patients with CC genotype of rs1045485 were more likely to have HER2 positive breast cancer than those with GG genotype [OR=2.93, 95% CI (1.0 4-8.26)]. In addition, CC genotype of D302H was associated with a decreased risk of breast cancer to 48% [OR=0.52, 95% CI (0.30-0.90)] whereas no significant association was found between rs10931936 and breast cancer. Haplotype analysis indicated C-C haplotype is associated with the decreased risk of breast cancer [(OR=0.69, 95% CI (0.52-0.91)]. Conclusion Our data showed a protective effect for CC genotype of rs1045485 variant and C-C haplotype of rs10931936- rs104548 in CASP8 in association with the decrease risk of breast cancer whereas rs10931936 showed no significant association. CAS8 rs1045485 polymorphism may be a candidate genetic marker to evaluate risk of breast cancer. However, further larger studies can confirm such findings.