Association of programmed death‐1 gene polymorphisms with the risk of basal cell carcinoma

Abstract

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.

Programmed cell death 1 (PDCD1) gene haplotypes and susceptibility of patients to basal cell carcinoma

“…However, the role of PD1.6 in susceptibility to cancer is not clearly reported yet. In previous study on the effects of PD1.3 and PD1.5 SNPs on BCC susceptibility, we observed that G allele of PD1.3 and AC haplotype of PDCD1 were significantly associated with BCC in the Iranian population [28]. In our knowledge, the roles of PD1.1 and PD1.6 SNPs in susceptibility to BCC are not identified so far.…”

“…risks of several cancers such as bladder, breast, lung, and pancreatic cancers [32]. The upregulation of PD-1 is approved in various cancers, while its downregulation can lead to defect in tolerance to self-antigens [28]. Although several risk factors have been proposed to BCC development, genetic agents may have fundamental roles in BCC susceptibility like other cancers [33].…”

“…PD1.1 G/A (rs36084323) is located in the promoter region (nucleotide position-538 from transcription start site) of PDCD1 gene [36,37]. Although there is a few reports pointing the impacts of PD-1 SNPs in BCC susceptibility in different populations [28], some studies have indicated PD1.1 role in developing different cancers [26]. Gomez et al revealed that AA genotype of PD1.1 was significantly correlated to the progression of cutaneous melanoma [38].…”

“…Genome wide association studies (GWAS) have indicated that mutations in genes encoding immuno-inhibitor agents are involved in disrupting immune reactions to developing tumors and subsequently participate in the progressions of different tumors [24,25]. Several lines of evidence indicate that PDCD1 SNPs, such as PD1.1, PD1.3, PD1.5, PD1.6, and PD1.9, may be effective in the development of different cancers and autoimmune disorders [26][27][28][29]. PD1.1 SNP may contribute to the progression of colon cancer [30].…”

PD-1 gene rs10204525 and rs7421861 polymorphisms are associated with increased risk and clinical features of esophageal cancer in a Chinese Han population

“…For example, the rs2227981, rs2227982, and rs3608432 polymorphisms were related to lung adenocarcinoma risk and prognosis [31]. However, no associations were observed in basal cell carcinoma [32]. The PD-1.5 C/T polymorphism increased the risk of cervical [33], lung [34], gastric [35], colon [36], thyroid cancers [37].…”