TRUNCAL TUMOR SITE IS ASSOCIATED WITH HIGH-RISK OF MULTIPLE BASAL-CELL CARCINOMA AND IS INFLUENCED BY GLUTATHIONE-S-TRANSFERASE, GSTT1, ANDCYTOCHROME-P450, CYP1A1 GENOTYPES, AND THEIR INTERACTION

Basal cell carcinoma (BCC) places increasing burdens on clinicians; in cidence is rising and patients may develop multiple primary tumors, Al though UV exposure is critical, many patients develop tumors at less-e xposed sites, such as the trunk, suggesting a genetic predisposition, We previously showed that polymorphism in loci encoding the detoxifyin g enzymes, glutathione S-transferase (GSTM1, GSTM3, GSTT1) and cytochr ome P450 (CYP2D6, CYP1A1) influences susceptibility to BCC, We now des cribe a case-control approach in 345 patients with BCC that examines t he role of these polymorphisms and patient characteristics (age, gende r, skin type, hair color, eye color, smoking, occupation) in determini ng susceptibility to truncal tumors, GST and CYP genotypes were identi fied using polymerase chain reaction-based methods. Patients with one or more truncal tumors were significantly younger (p = 0.0170) than th ose with no truncal tumors, Male gender also appeared more common in t he truncal tumor group, although this did not achieve significance (p = 0.0925), Patients whose first tumor was truncal had significantly mo re tumors (p = 0.0297). GSTT1 null (p = 0.0245, odds ratio 2.24) and C YP1A1 Ile/Ile (p = 0.0386, odds ratio 2.86) were associated with trunc al site after correction for age and gender, The combination, GSTT1 nu ll and CYP1A1 Ile/Ile. was particularly significant (p = 0.0059, odds ratio = 2.95), These effects were present after correction for tumor n umbers, These data show first, patients with truncal tumors constitute a high-risk group for BCC, second, a significant genetic influence on BCC site, and third, a significant interaction between GSTT1 and CYP1 A1 genotypes.