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  • Title: The Impact of CASP8 rs10931936 and rs1045485 Polymorphisms as well as the Haplotypes on Breast Cancer Risk: A Case-Control Study.
    Author: Vahednia E, Shandiz FH, Bagherabad MB, Moezzi A, Afzaljavan F, Tajbakhsh A, Kooshyar MM, Pasdar A.
    Journal: Clin Breast Cancer; 2019 Oct; 19(5):e563-e577. PubMed ID: 31362911.
    Abstract:
    INTRODUCTION: Single nucleotide polymorphisms account for most genetic predispositions to breast cancer in the general population. Because of the lack of studies concerning the 2 common polymorphisms in caspase 8 (CASP8), namely rs104548 and rs10931936 in Iranian population, we evaluated the association of these 2 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 using an amplification refractory mutation system and polymerase chain reaction restriction fragment length polymorphism, respectively. PHASE version 2 (Matthew Stephens) was used to estimate the frequencies of haplotypes. Statistical analysis was performed using SPSS 16.0 (SPSS Inc). RESULTS: Although hormone receptors and the molecular profile did not indicate any significant association with different genotypes (P > .05), patients with CC genotype of rs1045485 were more likely to have HER2-positive breast cancer than those with GG genotype (odds ratio [OR], 2.93; 95% confidence interval [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. CASP8 rs1045485 polymorphism might be a candidate genetic marker to evaluate risk of breast cancer. However, further larger studies can confirm such findings.
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