No 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.

The identification of clinically relevant, active immunomodulatory agents is important for developing immunotherapeutic approaches to chronic lymphocytic leukemia (CLL) and other B-cell lymphomas that are not curable with conventional chemotherapy. In this investigation, the imidazoquinoline Toll-like receptor (TLR)-7/8 agonist, imiquimod, was found to mediate the clearance of a lymphomatous skin lesion in a CLL patient. Imidazoquinolines also activated TLR-7/8 signaling pathways, resulting in increased expression of costimulatory molecules on circulating tumor cells. These observations extend the therapeutic spectrum of imiquimod to cutaneous B-cell lymphomas and suggest the use of TLR-7/8 agonists in CLL immunotherapy.