Associations between ultraviolet radiation, basal cell carcinoma site and histology, host characteristics, and rate of development of further tumors.

BACKGROUND: Patients with basal cell carcinoma (BCC) frequently develop further tumors during follow-up. OBJECTIVE: We sought to elucidate the relative effects of pattern of ultraviolet radiation exposure, and site and histologic type of the first tumor, on the rate of increase in BCC numbers. METHODS: We used negative binomial regression analysis to study the association of selected variables on the rate of increase in BCC numbers in 266 Caucasian patients who first presented with a tumor on the head/neck or trunk with nodular or superficial histology. RESULTS: Patients with an initial truncal BCC with superficial histology demonstrated significantly faster increases in BCC numbers than did patients with other site and histology combinations. CONCLUSIONS: These data indicate that site and histology define subsets of patients with BCC.

Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients.

Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (< or =7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.

PTCH polymorphism is associated with the rate of increase in basal cell carcinoma numbers during follow-up: preliminary data on the influence of an exon 12-exon 23 haplotype.

After first presentation with a basal cell carcinoma (BCC), patients demonstrate interindividual diversity in the rate of development of further BCCs (number/year of follow-up). The mechanism for this variation is unknown. In this study, we evaluated whether PTCH variants mediate this phenomenon. We used negative binomial regression analysis to identify associations between BCC numbers/year and host characteristics, parameters of exposure to ultraviolet radiation (UVR), and PTCH exon 12(1686) C/T, intron 15(2560+9) G/C, and exon 23(3944) C/T genotypes and haplotypes in 279 BCC cases who presented with an initial tumor on the head/neck. PTCH genotypes were not significantly associated with BCCs/year, although cases with two copies of the C1686-C3944 haplotype developed significantly fewer BCCs/year than those without this haplotype (rate ratio = 0.44; 95% CI = 0.27-0.71). Cases with one copy of T1686-T3944 developed more BCCs/year (rate ratio = 2.46; 95% CI = 1.27-3.97) than those without the haplotype. We found no significant associations between BCCs/year and the other PTCH haplotypes studied. We reexamined the association of C1686-C3944 with BCCs/year in a model that included UVR exposure parameters (sunburning in childhood, sunbathing score, intermittency of exposure between 40 and 60 years of age, exposure in hours/year) and skin type, gender, and age at first presentation. The association between C1686-C3944 and BCCs/year remained significant (rate ratio = 0.44; 95% CI = 0.26-0.73 for two copies of the haplotype). The data show that allelic variation in PTCH contributes to the rate of development of BCC.

Associations between UVR exposure and basal cell carcinoma site and histology.

While sunlight is critical in basal cell carcinoma (BCC) pathogenesis the relationship between exposure and tumor site and histology is unclear. We determined if tumor site (trunk or head/neck) or histology (nodular or superficial) is determined by exposure pattern. In 66 cases with truncal and 362 patients with head/neck BCC at first presentation, average hours exposure/year, intermittency score, childhood sunburning and skin type were not significantly associated with tumor site or histology. However, often sunbathing was associated with a five-fold increased risk of truncal BCC. Average sunbathing score was significantly greater in 22 cases with truncal compared with 325 cases with head/neck nodular tumors and also in 44 cases with superficial truncal compared with superficial head/neck BCC. Thus, sunbathing determined tumor site but not histology.

Combined effects of gender, skin type and polymorphic genes on clinical phenotype: use of rate of increase in numbers of basal cell carcinomas as a model system.

Patients with a basal cell carcinomas (BCC) have an increased risk of further tumors. We studied the individual and combined impact of gender, skin type and allelic genes cytochrome P450 (CYP2D6), vitamin D receptor (VDR), tumor necrosis factor-alpha, TNF-alpha) on the rate of increase in BCC numbers after first presentation. Individually, male gender, skin type 1, CYP2D6 EM, VDR TT and TNF-alpha GG were associated with more BCC/year (rate ratio (RR) 1.20-1.36) while RR for associations of combinations of two, three and four variables were greater than in their reference categories (RR 1.32-1.90, 2.20-2.84, 3.06-5.49, respectively). The data show that different factors mediate the numbers of BCC/year in males and females and, the individual contributions of variables to risk is modest.