Interaction of polymorphisms in xeroderma pigmentosum group C with cigarette smoking and pancreatic cancer risk

Abstract

The aim of the present study was to evaluate the association between xeroderma pigmentosum group C (XPC) polymorphisms and pancreatic cancer (PC) risk. A total of 7 XPC tagging SNPs (tag-SNPs) were selected from the International HapMap Project Databases (rs2228001A/C, rs2470353G/C, rs2228000C/T, rs3731114C/G, rs3729587G/C, rs2607775C/G and rs3731055G/A) and were genotyped in 205 patients with PC and 230 non-cancer control subjects using a SNaPshot assay. The C allelic gene frequency of rs2470353 was higher in patients with PC compared with that in the control group (P=0.003). Compared with the GG gene type, PC risk was increased in subjects with GC and GC+CC gene types (P=0.012 and P=0.006, respectively). PC risk increased 3.505-fold for the subjects who were heavy smokers (tobacco, ≥25 packets/year) with the GC+CC gene type (P=0.008). The G allelic gene frequency of rs2607775 was higher in PC patients compared with that in the control group (P=0.003). Compared with the CC gene type, PC risk increased in subjects with CG and CG+GG gene types (P=0.013 and P=0.005, respectively). Furthermore, PC risk increased 3.950-fold in subjects who were heavy smokers (tobacco, ≥25 packets/year) with the CG+GG gene type (P=0.001). Haplotype analysis further revealed that the CCC haplotype of rs2228000, rs3731114 and rs3729587 increased PC risk (odds ratio, 1.610; 95% confidence interval, 1.035–2.481; P=0.034). The present study revealed that XPC gene polymorphisms could increase the risk of PC in the study population, particularly among heavy smokers.

Comprehensive assessment of the association between XPC rs2228000 and cancer susceptibility based on 26835 cancer cases and 37069 controls

“…Furthermore, we excluded 64 articles due to the question of ‘lack of specific data or normal group’, ‘not in line with HWE’ or ‘cohort’. Finally, we identified a total of 71 eligible case–control studies from the 64 retrieved articles [1,2,4,10,11,27–85] for pooling analysis. We summarized some basic information in Table 1 and presented the flow chart in Figure 1.…”

“…For instance, there are a total of 33 articles with 14877 cases and 17888 controls [1,28,30–32,36,39,42,44,45,47,48,50,54–56,60,64–66,68–70,72,75–79,82,93–95] for the prior meta-analysis of He et al in 2013 [15]. In this study, we excluded two articles regarding bladder cancer [95] and cutaneous melanoma [94] because the genotype distribution in the control group is not in line with the HWE, and we added 32 other published articles [4,10,11,27,29,33–35,37,38,40,41,43,46,49,51,52,57–59,61–63,67,71,73,74,80,81,83–85]. Our pooling data from eight case–control studies showed the genetic correlation between XPC rs2228000 and increased risk of bladder cancer under the allelic, homozygotic, heterozygotic, dominant, and recessive models, which is partly consistent with the positive data of He et al (2013) [15] under the homozygotic and recessive models from four case–control studies.…”

“…Within the XPC gene, three common variants, including rs2228000 (C21151T) of exon 8, rs2228001 (A33512C) of exon 15, and poly-AT insertion/deletion polymorphism (PAT −/+ ) of intron 9, were identified [4,9–11]. XPC rs2228000 results in a substitution of alanine for valine in position 499 (Ala499Val), while rs2228001 leads to a transversion from lysine to glutamine in position 939 (Lys939Gln) [4,9–11]. The present study investigated the potential genetic role of nonsynonymous XPC rs2228000 in the risk of different clinical types of cancer by pooling published studies with inconclusive conclusions.…”

DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome

“…Similarly, Figure 6b depicts how a rare single nucleotide variant (SNV) at initiator codon of SUMF1 gene, which leads to multiple sulfatase deficiency (52), simultaneously disrupts a YY1 BS with unknown functional consequences. In Figure 6c, a common risk variant of pancreatic cancer at intronic region of XPC gene also greatly weakens CTCF BS (53). In all examples, DNABERT consistently shows highest attention at/around the variants of interest.…”

Xeroderma Pigmentosum Complementation Group C (XPC): Emerging Roles in Non-Dermatologic Malignancies

“…XPC may play a role as a risk factor for developing pancreatic cancer. As summarized in Table 1 , some XPC polymorphisms have been described as increasing pancreatic cancer risk, particularly in smokers with the rs2470353 and rs2607775 variants ( 101 ). However, one study suggested a protective role of the XPC -PAT polymorphism (PAT +/+) in pancreatic cancer risk ( 100 ).…”