Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin

• Published in: Carcinogenesis (New York) Vol. 27; no. 8; pp. 1676 - 1681
• Main Authors: Thirumaran, Ranjit Kumar, Bermejo, Justo Lorenzo, Rudnai, Peter, Gurzau, Eugene, Koppova, Kvetoslava, Goessler, Walter, Vahter, Marie, Leonardi, Giovanni S., Clemens, Felicity, Fletcher, Tony, Hemminki, Kari, Kumar, Rajiv
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2006; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Basal Cell - epidemiology; Carcinoma, Basal Cell - genetics; Case-Control Studies; Cell Cycle Proteins - genetics; Child; Child, Preschool; Dermatology; DNA Repair; Female; Genetic Predisposition to Disease; Genotype; Humans; Hungary - epidemiology; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neoplasm Proteins - genetics; Nuclear Proteins - genetics; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Romania - epidemiology; Skin Neoplasms - epidemiology; Skin Neoplasms - genetics; Slovakia - epidemiology; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet Rays - adverse effects; Hungary; Romania; Slovakia; Skin disease; Basal cell carcinoma; DNA; Malignant tumor; Single nucleotide polymorphism; DNA repair; Repair gene
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgi381

In addition to environmental exposures like UV radiation and, in some cases, arsenic contamination of drinking water, genetic factors may also influence the individual susceptibility to basal cell carcinoma of skin (BCC). In the present study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for one polymorphism in each of seven DNA repair genes. The variant allele for T241M (C>T) polymorphism in the XRCC3 gene was associated with a decreased cancer risk [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.61–0.88; P = 0.0007, multiple testing corrected P = 0.004]. The risk of multiple BCC was significantly lower among variant allele carriers than in non-carriers (P = 0.04). Men homozygous for the C-allele for E185Q (G>C) polymorphism in the NBS1 gene showed an increased BCC risk (OR, 2.19; 95% CI, 1.23–3.91), but not women (OR, 0.84; 95% CI, 0.49–1.47). In men, the age and nationality adjusted OR for the genotype CC (XRCC3)/CC (NBS1) was 8.79 (95% CI, 2.10–36.8), compared with the genotype TT (XRCC3)/GG (NBS1). The data from this study show overall risk modulation of BCC by variant allele for T241M polymorphism in XRCC3 and gender-specific effect by E185Q polymorphism in NBS1.