Presentation with multiple cutaneous basal cell carcinomas: Association ofglutathione S-transferase and cytochrome P450 genotypes with clinical phenotype
S. Ramachandran et al., Presentation with multiple cutaneous basal cell carcinomas: Association ofglutathione S-transferase and cytochrome P450 genotypes with clinical phenotype, CANC EPID B, 8(1), 1999, pp. 61-67
We previously reported associations between numbers of basal cell carcinoma
s (BCCs) and glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P45
0 (CYP2D6) genotypes, Thus, although GSTM1 AB is protective, GSTM1 null, GS
TT1 null, and CYP2D6 EM are associated with increased numbers of lesions. H
ere, we examine the hypothesis that these genotypes are associated with hig
h-risk subgroups, The subgroup studied comprised 119 patients with more tha
n one previously unidentified BCC at first or later presentations [multiple
presentation phenotype (MPP)], These patients were part of a group of 773
BCC patients that also included 567 patients with one BCC and 87 patients w
ith only one lesion at each presentation [single presentation phenotype (SP
P)] but who developed multiple BCCs, The number of tumors in the MPP was si
gnificantly greater than that in the SPP groups. In the MPP but not SPP pat
ients, GSTM1 AB, GSTT1 null, and CYP2D6 EM were significantly associated wi
th BCC numbers, suggesting that previously observed associations reflect th
e influence of these genes only in the MPP cases. There was no evidence tha
t MPP patients had received more UV exposure. We also determined whether th
e increased numbers of BCC in the MPP cases reflects an association with th
e truncal tumor phenotype, The values of the rate ratios indicated that the
MPP is a marker for the risk of many BCCs, although the combination of MPP
and a truncal tumor is a higher-risk phenotype, The data demonstrate the h
eterogeneity in BCC patients, which reflects differences in genetic factors
that determine skin response to UV.