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 presentation with a cluster of new basal cell carcinoma (BCC) comprise a subgroup, termed multiple presentation phenotype (MPP), that is at increased risk of developing further 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 clusters (multiple cluster MPP) and 113 cases with only one cluster (single cluster 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) exposure in these groups was similar. We determined whether the multiple cluster MPP was associated with characteristics associated with sensitivity to UV or glutathione S-transferase (GST) GSTT1, GSTM1, cytochrome P450 (CYP) CYP2D6, tumour necrosis factor (TNF)-alpha and vitamin D receptor (VDR) genotypes previously associated with BCC presentational phenotypes. While the frequencies of blue eyes and male gender were greater in multiple cluster than 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%) 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%, respectively). The odds ratios for the individual associations of CYP2D6 EM and GSTT1 null with the multiple cluster MPP were relatively larger; 15.5 and 7.39, respectively. TNF-alpha and VDR genotypes were not associated with multiple cluster MPP. We propose that the MPP is not the consequence of excessive UV exposure but rather reflects the presence of a distinct BCC subgroup which is defined by combinations of risk genes.
Ramachandran
S
S
Centre for Cell and Molecular Medicine and Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire, UK.
Fryer
A A
AA
Smith
A G
AG
Lear
J T
JT
Bowers
B
B
Hartland
A J
AJ
Whiteside
J R
JR
Jones
P W
PW
Strange
R C
RC
D000483:Alleles; D002280:Basal Cell Carcinoma / Q000201:enzymology / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase