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

• Published in: Environmental and molecular mutagenesis 2004, Vol.44 (5), p.469-476
• Main Authors: Strange, Richard C., El-Genidy, Noha, Ramachandran, Sudarshan, Lovatt, Tracy J., Fryer, Anthony A., Smith, Andrew G., Lear, John T., Ichii-Jones, Fumiyo, Jones, Peter W., Hoban, Paul R.
• Format: Article
• Language: English
• Subjects: Adult; basal cell carcinoma; BCC numbers; Biological and medical sciences; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - pathology; Exons - genetics; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetics of eukaryotes. Biological and molecular evolution; Genotype; haplotypes; Haplotypes - genetics; Humans; Medical sciences; Membrane Proteins - genetics; Middle Aged; Patched Receptors; Patched-1 Receptor; polymorphism; Polymorphism, Single Nucleotide - genetics; PTCH; Receptors, Cell Surface; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Toxicology; Ultraviolet Rays
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.20068

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 121686 C/T, intron 152560+9 G/C, and exon 233944 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. Environ. Mol. Mutagen., 2004. © 2004 Wiley‐Liss, Inc.