Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Clin Breast Cancer. 2019 Oct;19(5):e563-e577. doi: 10.1016/j.clbc.2019.02.011. Epub 2019 May 31.
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.
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).
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).
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.
单核苷酸多态性在普通人群中导致了大多数乳腺癌的遗传易感性。由于缺乏关于半胱氨酸蛋白酶 8（CASP8）中 2 个常见多态性（rs104548 和 rs10931936）的研究，我们评估了这 2 个多态性及其单倍型与乳腺癌和分子特征的关联。
采集了 287 名乳腺癌患者和 490 名对照者的血样。使用扩增受阻突变系统和聚合酶链反应限制性片段长度多态性，分别对 rs1045485 和 rs10931936 进行基因分型。使用 PHASE 版本 2（Matthew Stephens）来估计单倍型的频率。使用 SPSS 16.0（SPSS Inc）进行统计分析。
尽管激素受体和分子特征与不同基因型无显著相关性（P>.05），但与 GG 基因型相比，rs1045485 的 CC 基因型患者更可能患有 HER2 阳性乳腺癌（比值比[OR]，2.93；95%置信区间[CI]，1.04-8.26）。此外，D302H 的 CC 基因型与乳腺癌风险降低 48%相关（OR，0.52；95%CI，0.30-0.90），而 rs10931936 与乳腺癌之间无显著相关性。单倍型分析表明，C-C 单倍型与乳腺癌风险降低相关（OR，0.69；95%CI，0.52-0.91）。
我们的数据表明，rs1045485 变体的 CC 基因型和 rs10931936-rs104548 的 C-C 单倍型在 CASP8 中与乳腺癌风险降低相关，具有保护作用，而 rs10931936 则无显著相关性。CASP8 rs1045485 多态性可能是评估乳腺癌风险的候选遗传标志物。但是，进一步的大规模研究可以证实这些发现。
