Genetic factors determining cutaneous basal cell carcinoma phenotype

Background. Basal cell carcinoma (BCC) patients demonstrate considerable ph enotypic diversity. The basis of this heterogeneity is poorly understood. W e have shown that presentational phenotypes are associated with BCC numbers . Thus, patients with a cluster of new BCC at any presentation comprise a s ubgroup, termed MPP, that is at increased risk of developing numerous lesio ns. Patients with more than one cluster (multiple cluster MPP) are at parti cular risk. Procedure. We determined in a cohort of BCC cases, whether: (i) tumor accrual was altered after clustering; and (ii) multiple cluster MPP is associated with characteristics linked with sensitivity to UV or, GSTT1, GSTM1, GSTM3, GSTP1, MC1R, CYP2D6, TNF-alpha, and VDR genotypes previously associated with BCC presentational phenotypes. Results. (i) After clusteri ng BCC accrual increased; and (ii) exposure to UV in single and multiple cl uster MPP cases were similar. In multiple cluster cases, mean age at first presentation with a single tumor occurred earlier and, the frequencies of C YP2D6 EM (94.4%) and GSTT1 null (41.2%) were significantly greater (P=0.028 and P=0.004) than in single cluster cases (67.1 and 14.3%). The odds ratio s for these associations with the multiple cluster MPP were large; 15.5 and 7.39, respectively. Conclusions. The finding of clusters of new, primary B CC is a critical event that is followed by markedly increased accrual of fu rther tumors. Clustering occurs at a relatively late age and may be associa ted with a failure in immune surveillance. We propose the MPP is not the co nsequence of excessive UV exposure but reflects the presence of a distinct BCC subgroup defined by a combination of risk genes. Med. Pediatr. Oncol. 3 6:559-563, 2001. (C) 2001 Wiley-Liss, Inc.