Basal cell carcinomas: association of allelic variants with a high-risk subgroup of patients with the multiple presentation phenotype

Previous studies have shown that patients who present at first or a later p resentation with a cluster of new basal cell carcinoma (BCC) comprise a sub group, termed multiple presentation phenotype (MPP), that is at increased r isk of developing farther lesions. in this study we examined the hypothesis that patients who develop multiple clusters are a high-risk; subgroup. We found, in a total group of 926 BCC patients, 32 patients with 2-5 BCC clust ers (multiple cluster MPP) and 113 cases with only one cluster (single clus ter MPP), Multiple cluster MPP cases had mean of 11.3 BCC compared with 3.7 in single cluster MPP cases during similar follow-up, Ultraviolet (UV) exp osure in these groups was similar. We determined whether the multiple clust er MPP was associated with characteristics associated with sensitivity to U V or glutathione S-transferase (GST) GSTT1, GSTM1, cytochrome P450 (CYP) CY P2D6, tumour necrosis factor (TNF)-alpha and vitamin D receptor (VDR) genot ypes previously associated with BCC presentational phenotypes. While the fr equencies of blue eyes and male gender were greater in multiple cluster tha n single cluster cases, these differences were not significant, In multiple cluster cases, mean age at first presentation with single tumours occurred earlier and the frequencies of CYP2D6 extensive metabolizer (EM) (94.4%) a nd GSTT1 null (41.2%) were significantly greater (P = 0.028 and P = 0.004) than in single cluster cases (67.1% and 14.3%, respectively). The odds rati os for the individual associations of CYP2D6 EM and GSTT1 null with the mul tiple cluster MPP were relatively large; 15.5 and 7.39, respectively. TNF-a lpha and VDR genotypes were not associated with multiple cluster MPP. We pr opose that the MPP is not the consequence of excessive UV exposure but rath er reflects the presence of a distinct BCC subgroup which is defined by com binations of risk genes, Pharmacogenetics 11:247-254 (C) 2001 Lippincott Wi lliams & Wilkins.