Fathi Farshid, Ebrahimi Milad, Eslami Asma, Hafezi Hossein, Eskandari Nahid, Motedayyen Hossein
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Faculty of Medicine, Department of Immunology, Shahed University, Tehran, Iran.
Int J Immunogenet. 2019 Dec;46(6):444-450. doi: 10.1111/iji.12447. Epub 2019 Jul 10.
Environmental and genetic factors play a fundamental role in the pathogenesis of basal cell carcinoma (BCC) defined as the most common cancer of skin. Programmed death-1 (PD-1), encoded by programmed cell death-1 (PDCD1) gene, serves as an inhibitory molecule in the suppression of immune responses and a risk factor in the development of different cancers. In this study, we investigated the role of two single nucleotide polymorphisms (SNPs) within PDCD1 gene, and haplotypes defined by these SNPs, in the development of BCC in an Iranian population. Whole blood samples were obtained from 210 BCC and 320 healthy subjects. Genomic DNA was extracted from whole blood samples, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype determinations of PD1.3 (rs11568821) and PD1.5 (rs2227981) SNPs, and 4 haplotypes were constructed by PDCD1 SNPs. The frequency of G allele of PD1.3 was significantly higher in BCC patients than healthy subjects (p < 0.02), while these significant differences were not observed in the frequencies of PD1.5 alleles between BCC and healthy subjects. Moreover, we found that there were no statistically significant differences in PD1.3 and PD1.5 genotypes between BCC and control groups. Of all estimated haplotypes for PDCD1, only AC haplotype was associated with BCC (OR = 0.22, 95% CI = 0.06-0.79, p < 0.01). These findings suggest that PD1.3G allele and AC haplotype of PDCD1 contribute to BCC in the Iranian population. However, further studies in different populations with larger sample size are required to confirm this study.
环境和遗传因素在基底细胞癌（BCC，被定义为最常见的皮肤癌）的发病机制中起着根本性作用。程序性死亡1（PD-1）由程序性细胞死亡1（PDCD1）基因编码，是免疫反应抑制中的一种抑制性分子，也是不同癌症发生发展的一个风险因素。在本研究中，我们调查了PDCD1基因内两个单核苷酸多态性（SNP）以及由这些SNP定义的单倍型在伊朗人群基底细胞癌发生中的作用。从210例基底细胞癌患者和320名健康受试者中采集全血样本。从全血样本中提取基因组DNA，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对PD1.3（rs11568821）和PD1.5（rs2227981）SNP进行基因分型测定，并由PDCD1 SNP构建4种单倍型。基底细胞癌患者中PD1.3的G等位基因频率显著高于健康受试者（p < 0.02），而基底细胞癌患者与健康受试者之间PD1.5等位基因频率未观察到显著差异。此外，我们发现基底细胞癌组与对照组之间PD1.3和PD1.5基因型无统计学显著差异。在所有估计的PDCD1单倍型中，只有AC单倍型与基底细胞癌相关（OR = 0.22，95%CI = 0.06 - 0.79，p < 0.01）。这些发现表明，PD1.3的G等位基因和PDCD1的AC单倍型在伊朗人群基底细胞癌发生中起作用。然而，需要在不同人群中进行更大样本量的进一步研究来证实本研究结果。
