XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk.
Baccarelli-A; Calista-D; Minghetti-P; Marinelli-B; Albetti-B; Tseng-T; Hedayati-M; Grossman-L; Landi-G; Struewing-JP; Landi-MT
Br J Cancer 2004 Jan; 90(2):497-502
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)=1.5, 95% confidence interval (CI)=0.9-2.5 for 312Asn; OR=1.3, 95% CI=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 (>50 years) subjects (OR=3.4, 95% CI=1.6-7.3 for 312Asn; OR=2.3, 95% CI=1.1-4.9 for 751Gln). The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic naevi (OR=2.6, 95% CI=1.1-6.4). Subjects with low tanning ability and XPD variants exhibited a nonsignificant increase of melanoma risk (OR=2.3, 95% CI=0.7-7.0 for 312Asn; OR=3.0, 95% CI=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.
Age-factors; Humans; Men; Women; Genetic-factors; Genetics; Etiology; Risk-factors; Skin-cancer; Proteins; Cancer;
Author Keywords: Cutaneous malignant melanoma; XPD; ERCC2; DNA repair; Age
Dr MT Landi, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, 6120 Executive Blvd., Bethesda, MD 20892-7236
British Journal of Cancer
Johns Hopkins University