Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population

Abstract

(1-5) DNA repair enzymes are involved in repairing damaged DNA and at least four pathways operate on specific types of DNA damage: the BER, (6)(7)(8) NER, (9) DSBR (10,11) and MMR (12) pathways. Enzymes involved in BER include XRCC1, those involved in NER include XPC, XPD, ERCC1, those involved in DSBR include BRCA1, BRCA2 and XRCC3, and those involved in MMR include MLH1, MSH2, PMS2 and MSH6. Polymorphisms of DNA repair genes may also alter protein function and the capacity to repair damaged DNA, which may be associated with risk of developing cancer.(1-3) Cancers such as breast cancer, (13)(14)(15) prostate cancer, (16) lung cancer,acute myeloblastic leukemia, (18) colon cancer, (19) stomach cancer (20,21) and SCC of the head and neck (22) are associated with DNA repair gene polymorphisms, and skin cancer is associated with polymorphisms in XRCC1, Various SNP are known to occur in XRCC1 (1,3,5,27,28) and they are thought to cause the occurrence of skin cancer through altering the function of BER. In vivo and in vitro, the XRCC1 gene repairs chromosomes directly by acting on SSB or indirectly through the BER pathway. Cells deficient in the XRCC1 gene are known to be susceptible to a wide variety of genotoxins and subsequently sustain translocations and loss of chromosomes. (10) But they also reported that in patients with XRCC1 Arg399Gln(G > A), lifetime sunburn exposure of more than four times is a risk factor for SCC.Skin cancer is increasing with the lengthening of people's life spans, environmental pollution and destruction of the ozone layer. Of all skin cancers, BCC and SCC occur most frequently. In the present study we test whether the XRCC1 polymorphisms are associated with an increased risk of SCC and BCC of the skin in the Korean population. Materials and methodsStudy population. The study population was composed of 212 patients (mean age ± SD, 68.98 ± 12.6 years; age range, 36-100 years) with skin cancer (114 BCC, 98 SCC) and 207 control subjects (mean age ± SD, 46.42 ± 16.6 years; age range, 21-85 years). Patients with skin cancer were enrolled and recruited from We subcategorized the patients according to the location of cancer lesions and sun exposure time. The frequencies of SCC were: head and neck, 65.9%; body, 8.5%; and limb, 12.7%. Those of BCC were: head and neck, 95.9%; body, 2.7%; and limb, 0.9%. Irrespective of BCC and SCC, compared to the control group patients with outdoor jobs and sun exposure times of more than 4 h/day had a higher proportion of skin cancer (4.6 vs 51.6% and 4.5 vs 46.9%, respectively). All of the cases underwent skin cancer surgery and were histologically confirmed.The controls (n = 207) were healthy individuals without any history of premalignant skin lesions or other malignant disorders who visited Bundang CHA General Hospital. The institutional review board of Bundang CHA General Hospital approved this genetic study in January 1998. All of the patients and controls

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

“…It was suggested that the XRCC1 Arg399Gln polymorphism was also associated with other cancers in Asian population, which included colorectal cancer, 42 lung cancer, 43 basal cell carcinoma 44 and so on. The study by Wang et al 42 indicated that the XRCC1 399Gln allele was associated with a significantly increased rectal cancer risk among men.…”

“…Besides, XRCC1 Arg399Gln polymorphism may alter the risk of lung cancer in women nonsmokers in China. 43 Kang et al 44 found that the XRCC1 Arg399Gln polymorphism was associated with an increased risk of basal cell carcinoma. 44 Given the important roles of XRCC1 gene, it is biologically plausible that XRCC1 polymorphism may modulate the risk of PCa.…”

“…43 Kang et al 44 found that the XRCC1 Arg399Gln polymorphism was associated with an increased risk of basal cell carcinoma. 44 Given the important roles of XRCC1 gene, it is biologically plausible that XRCC1 polymorphism may modulate the risk of PCa. The XRCC1 Arg399Gln polymorphism was shown to be correlated with DNA repair activity and associated with susceptibility to various cancers, including PCa.…”

Single nucleotide polymorphisms in DNA repair genes and putative cancer risk

“…Mixed results were also obtained for other cancer entities. While a protective effect of the XRCC1 variant has been reported for nasopharyngeal carcinoma ) and squamous cell carcinoma (Kang et al 2007), an increased risk was observed for salivary gland carcinoma (Ho et al 2007). For alleles 280 and 399, no significant association between the variant form and risk of cancers including lung cancer (Hao et al 2006;Hung et al 2005;Yin et al 2009), salivary gland carcinoma (Ho et al 2007) and nasopharyngeal carcinoma ) is reported, suggesting that the XRCC1 SNPs at position 280 and 399 do not play a major role for cancer risk.…”

“…For alleles 280 and 399, no significant association between the variant form and risk of cancers including lung cancer (Hao et al 2006;Hung et al 2005;Yin et al 2009), salivary gland carcinoma (Ho et al 2007) and nasopharyngeal carcinoma ) is reported, suggesting that the XRCC1 SNPs at position 280 and 399 do not play a major role for cancer risk. On the other hand, an increased cancer risk for the variant form of allele 399 was reported for squamous cell carcinoma (Kang et al 2007) and lung cancer (De Ruyck et al 2007;Wang et al 2015).…”