title: 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.
abstract: 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.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, University Hospital of North Staffordshire, Staffordshire, United Kingdom. paa00@keele.ac.uk
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.forename: Noha
authors.initials: N
authors.lastname: El-Genidy
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Lovatt
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Smith
authors.forename: John T
authors.initials: JT
authors.lastname: Lear
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Ichii-Jones
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jones
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hoban
mesh_terms: D000328:Adult; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface