Genetic factors determining cutaneous basal cell carcinoma phenotype.
BACKGROUND
Basal cell carcinoma (BCC) patients demonstrate considerable phenotypic diversity. The basis of this heterogeneity is poorly understood. We have shown that presentational phenotypes are associated with BCC numbers. Thus, patients with a cluster of new BCC at any presentation comprise a subgroup, termed MPP, that is at increased risk of developing numerous lesions. Patients with more than one cluster (multiple cluster MPP) are at particular risk.


METHODS
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 clustering BCC accrual increased; and (ii) exposure to UV in single and multiple cluster MPP cases were similar. In multiple cluster cases, mean age at first presentation with a single tumor occurred earlier and, the frequencies of CYP2D6 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 ratios for these associations with the multiple cluster MPP were large; 15.5 and 7.39, respectively.


CONCLUSIONS
The finding of clusters of new, primary BCC is a critical event that is followed by markedly increased accrual of further tumors. Clustering occurs at a relatively late age and may be associated with a failure in immune surveillance. We propose the MPP is not the consequence of excessive UV exposure but reflects the presence of a distinct BCC subgroup defined by a combination of risk genes.
Ramachandran
S
S
Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, North Staffordshire Hospital, Keele University, Staffordshire, England, UK.
Fryer
A A
AA
Strange
R C
RC
D002280:Basal Cell Carcinoma / Q000235:genetics*; D004739:England; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D012878:Skin Neoplasms / Q000235:genetics*