S. Ramachandran et al., Basal cell carcinomas: association of allelic variants with a high-risk subgroup of patients with the multiple presentation phenotype, PHARMACOGEN, 11(3), 2001, pp. 247-254
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.