XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk

Abstract

We recently reported an association between low DNA repair capacity, measured through the host-cell reactivation assay, and melanoma risk in subjects with dysplastic naevi or low tanning ability. We investigated the genetic basis for these findings by analysing the Asp312Asn and Lys751Gln polymorphisms of the XPD (ERCC2) DNA repair gene in the same subjects. Similar to our previous report, no significant association between XPD polymorphisms and melanoma risk was found in 176 melanoma cases and 177 controls (odds ratio (OR) ¼ 1.5, 95% confidence interval (CI) ¼ 0.9 -2.5 for 312Asn; OR ¼ 1.3, 95% CI ¼ 0.8 -2.1 for 751Gln, adjusted for age, gender, dysplastic naevi and pigmentation characteristics). However, XPD variants were associated with increased risk in older (450 years) subjects (OR ¼ 3.4, 95% CI ¼ 1.6 -7.3 for 312Asn; OR ¼ 2.3, 95% CI ¼ 1.1 -4.9 for 751Gln). The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic naevi (OR ¼ 2.6, 95% CI ¼ 1.1 -6.4). Subjects with low tanning ability and XPD variants exhibited a nonsignificant increase of melanoma risk (OR ¼ 2.3, 95% CI ¼ 0.7 -7.0 for 312Asn; OR ¼ 3.0, 95% CI ¼ 1.0 -8.8 for 751Gln). DNA repair capacity was slightly decreased in subjects carrying 751Gln alleles. XPD variants may modify melanoma risk in subjects with specific host characteristics, such as older age, lack of dysplastic naevi or low tanning ability.

Polymorphisms in the DNA Repair GenesXPC, XPD, andXPGand Risk of Cutaneous Melanoma: a Case-Control Analysis

“…Although several previous studies have investigated the association between polymorphisms in NER genes and risk of cutaneous melanoma, most of the study sizes were relatively small, and the results were not consistent (8)(9)(10)(11)(12)(13)(14). Given potential roles of XP genes in repairing UV-induced DNA damage, we hypothesized that genetic variants in XP genes may contribute individually or collectively to risk of cutaneous melanoma.…”

XPD Lys751Gln and Asp312Asn Polymorphisms and Susceptibility to Skin Cancer: A Meta-Analysis of 17 Case-control Studies

“…After screening the titles and abstracts, only 20 potentially eligible articles were identified for further detailed evaluation. After full-text assessment of these articles, we included a total of 15 articles (Dybdahl et al, 1999;Winsey et al, 2000;Vogel et al, 2001;Yin et al, 2003;Baccarelli et al, 2004;Lovatt et al, 2005;Festa et al, 2005;Han et al, 2005;Thirumaran et al, 2006;Li et al, 2006;Millikan et al, 2006;Debniak et al, 2006;Povey et al, 2007;Kertat et al, 2008;Paszkowska-Szczur et al, 2013) in this meta analysis, including 9 studies for cutaneous melanoma (Winsey et al, 2000;Baccarelli et al, 2004;Han et al, 2005;Li et al, 2006;Millikan et al, 2006;Debniak et al, 2006;Povey et al, 2007;Kertat et al, 2008;Paszkowska-Szczur et al, 2013), 7 studies for basal cell carcinoma (Dybdahl et al, 1999;Vogel et al, 2001;Yin et al, 2003;Lovatt et al, 2005;Festa et al, 2005;Han et al, 2005;Thirumaran et al, 2006) and 1 for squamous cell carcinoma (Han et al, 2005). All articles were written in English.…”

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

“…1 Between 1940 and 2000 there was a progressive worldwide rise in the incidence of cutaneous melanoma. 2 The mortality rate from melanoma has increased from 2 per 100 000 in 1969 to 3 per 100 000 in 1999, and this was mainly because of a high mortality among men aged 65 years. 3 In the United States, approximately 64 939 new melanoma cases are predicted for 2008.…”

“…4 Phenotypic melanoma risk factors include age, 5 sunlight exposure 6 (particularly intense intermittent exposure), 5 family history of melanoma, dysplastic nevi or atypical nevi, number of nevi, skin sensitivity to sun, freckling, fair hair, eye and skin colour. 2 The role of molecular factors that could mediate susceptibility to and prognosis of sporadic melanoma is a subject of ongoing investigation. Polymorphisms associated with melanoma susceptibility or the course of disease have been described in genes involved in DNA repair, 7 in the regulation of skin pigmentation, such as the melanocortin-1 receptor gene, 8 in the production of proteins of the steroid and thyroid hormone superfamily, including vitamin D and the peroxisome proliferator-activated receptor genes, 9 or the detoxification of oxidative stress metabolites, such as the glutathione S-transferase genes.…”