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.

PTCH1 gene haplotype association with basal cell carcinoma after transplantation

“…We selected three frequent SNPs present in the PTCH1 gene: 23,24 exon 23 C>T 3944 , exon 12 C>T 1686 and intron 9 C>T 1336‐135 . Polymorphism C>T 3944 has been associated with breast cancer risk in women using oral contraceptives, 29 and with BCC in relation to population eumelanin–phaeomelanin status 25 …”

“…Somatic mutations in the PTCH1 gene or in one of the components of the SHH signalling pathway contribute to development of BCC and other types of cancers 18–22 . Moreover, recent publications suggest that allelic variation of the PTCH1 gene may also influence genetic susceptibility to BCC 23–26 …”

Sonic Hedgehog signaling in advanced prostate cancer

“…Further analysis revealed that activating or missense mutations in SMOH, a Hh coreceptor, are present in human basal cell carcinomas and medulloblastomas [63,64]. Additional data now exist suggesting various roles for the Hh pathway in breast, esophageal, lung, pancreatic, and stomach tumors [49,[64][65][66][67][68][69][70][71][72][73]. Thus it appears that the Hh pathway is affected in multiple tumor types.…”

Comparison of risk factors of single basal cell carcinoma with multiple basal cell carcinomas

“…One possible explanation could be the genetic susceptibility secondary to ethnic affinity. The genetic factors associated with mBCC, particularly PTCH gene polymorphism,[26] have been investigated in several studies; glutathione S -transferase, cytochrome P450 and TNF polymorphism have been suggested as other genetically determined risk factors for mBCC. [142425]…”