Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients.

Solid organ transplant recipients are at higher risk of nonmelanomaskin cancer (NMSC), especially basal cell carcinoma (BCC)and squamous cell carcinoma (SCC). Genetic alterations in the productionof detoxifying enzymes such as glutathione S-transferase(GST) and CYP1A1 may enhance this risk. We investigated the frequencyof GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1)and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and132 controls free from NMSC matched for type of transplanted organ,duration of transplantation, sex and age. Allele GSTP1*A was associatedwith a higher risk of NMSC [odds ratio (OR) 1.7 (1.1–2.5); P ¼0.017]. Homozygosity for allele GSTP1 Val105 was lower in cases [OR0.3 (0.1–0.8); P ¼ 0.012], especially in patients with SCC [OR 0.1(0.0–0.7); P ¼ 0.012]. A higher risk of BCC was found in patients withGSTM1 null/null [null/null versus A + B, OR 3.1 (1.4–6.8); P ¼0.003]. Analysis of allelism and interaction between allelic variantsshowed significant association between combined GSTM1 andCYP1A1 Val462 genotypes, where individuals homozygous for the riskallele GSTM1 null and carrying also the allele CYP1A1 Val462, showa higher risk of developing NMSC [OR 4.5 (1.1–21.4); P ¼ 0.03], especiallySCC [OR 6.5 (1.4–34.4); P ¼ 0.01]. GSTP1 polymorphisms areassociated with both BCC and SCC risk. GSTM1 polymorphismsseem to be involved in BCC risk, while GSTM1 null/null genotypecombined with CYP1A1 allele Val462 are associated with a higher riskfor SCC, indicating that allelism and/or interactions between allelicvariants at other loci may also influence the risk of NMSC, particularlySCC.