XRCC1 Arg194Trp polymorphism, risk of nonmelanoma skin cancer and extramammary Paget’s disease in a Japanese population

Abstract

The X-ray repair cross-complementing groups 1 gene plays an important role in base excision repair. At least three common single nucleotide polymorphisms frequently occur in this gene (Arg399Gln, Arg194Trp and Arg280His). Recent studies reported that these polymorphisms were associated with not only risk of visceral malignancy but also that of skin cancer such as basal cell carcinoma and squamous cell carcinoma, whereas the results of previous study vary among races. In this case–control study, we investigated whether these single nucleotide polymorphisms were associated with the risk of skin cancer in a Japanese population. The study population was composed of 197 patients with skin cancer (27 actinic keratoses, 47 basal cell carcinomas, 27 squamous cell carcinomas, 29 Bowen’s diseases, 46 malignant melanomas and 21 extramammary Paget’s diseases) and 93 control subjects. We genotyped two single nucleotide polymorphisms (Arg194Trp and Arg399Gln) using polymerase chain reaction-restriction fragments length polymorphism analysis. We found a significantly increased risk for basal cell carcinoma, squamous cell carcinoma and extramammary Paget’s disease associated with Arg194Trp [adjusted odds ratio (AOR) = 2.347, 3.587, 3.741, 95 % confidence interval (CI) 1.02–5.39, 1.19–10.8, 1.15–12.2, respectively]. We also found a significantly decreased risk for basal cell carcinoma associated with Gln399Gln (AOR = 0.259, 95 % CI 0.07–0.96). Our data suggest that the Arg194Trp polymorphism could be associated with nonmelanoma skin cancer and extramammary Paget’s disease risk in a Japanese population.

Identification of genetic alterations in extramammary Paget disease using whole exome analysis

“…Interestingly, rates of recurrence and secondary malignancies were increased in patients with MLH1/MSH2 mutations. In addition, single nucleotide polymorphisms (SNPs) in the DNA repair gene XRCC1 were associated with a higher risk of developing EMPD [4]. However, the molecular mechanisms underlying EMPD have not been fully elucidated.…”

Association between polymorphisms in DNA repair gene <em>XRCC1</em> and non-melanoma skin cancer risk: a meta-analysis

“…Figure 1 shows the selection process of this meta-analysis. The 10 articles included were conducted in 10 different countries: UK, 29 Denmark, 30 , 31 USA, 32 Sweden/Finland, 33 Sweden, 34 Korea, 35 Japan, 36 Germany, 37 and Taiwan (China). 38 Three were conducted in Asian populations and seven in Caucasian populations.…”

Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitylation after degradation of poly(ADP-ribose)

“…Studies of neural degenerative diseases demonstrate that the genesis of cerebellar interneurons requires XRCC1 (Lee et al, 2009). A spectrum of cancers, including ovarian, bladder, gastric, pancreatic, colorectal, skin and lung, have been reported with various XRCC1 polymorphisms (Cheng et al, 2012; Chiyomaru et al, 2012; Muñiz-Mendoza et al, 2012; Nakao et al, 2012; Wang et al, 2012; Zhi et al, 2012). A complete knockout of XRCC1 shows that it is essential for cell survival, and investigating the kinetics of polymorphisms of XRCC1 and their effects on the kinetics of other proteins used in this study would be useful for understanding the molecular mechanisms of tumorigenesis.…”