title: Truncal tumor site is associated with high risk of multiple basal cell carcinoma and is influenced by glutathione S-transferase, GSTT1, and cytochrome P450, CYP1A1 genotypes, and their interaction.
abstract: Basal cell carcinoma (BCC) places increasing burdens on clinicians; incidence is rising and patients may develop multiple primary tumors. Although UV exposure is critical, many patients develop tumors at less-exposed sites, such as the trunk, suggesting a genetic predisposition. We previously showed that polymorphism in loci encoding the detoxifying enzymes, glutathione S-transferase (GSTM1, GSTM3, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) influences susceptibility to BCC. We now describe a case-control approach in 345 patients with BCC that examines the role of these polymorphisms and patient characteristics (age, gender, skin type, hair color, eye color, smoking, occupation) in determining susceptibility to truncal tumors. GST and CYP genotypes were identified using polymerase chain reaction-based methods. Patients with one or more truncal tumors were significantly younger (p = 0.0170) than those with no truncal tumors. Male gender also appeared more common in the truncal tumor group, although this did not achieve significance (p = 0.0925). Patients whose first tumor was truncal had significantly more tumors (p = 0.0297). GSTT1 null (p = 0.0245, odds ratio 2.24) and CYP1A1 Ile/Ile (p = 0.0386, odds ratio 2.86) were associated with truncal site after correction for age and gender. The combination, GSTT1 null and CYP1A1 Ile/Ile, was particularly significant (p = 0.0059, odds ratio = 2.95). These effects were present after correction for tumor numbers. 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 CYP1A1 genotypes.
authors.affiliation: Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, U.K.
authors.forename: J T
authors.initials: JT
authors.lastname: Lear
authors.forename: A G
authors.initials: AG
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Bowers
authors.forename: A H
authors.initials: AH
authors.lastname: Heagearty
authors.forename: P W
authors.initials: PW
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Gilford
authors.forename: J
authors.initials: J
authors.lastname: Alldersea
authors.forename: R C
authors.initials: RC
authors.lastname: Strange
authors.forename: A A
authors.initials: AA
authors.lastname: Fryer
mesh_terms: D000368:Aged; D002280:Basal Cell Carcinoma / Q000453:epidemiology* / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics; D013899:Thoracic Neoplasms / Q000453:epidemiology* / Q000235:genetics
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase