Susceptibility to Basal Cell Carcinoma: Associations with PTCH Polymorphisms

Summary Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2318, 3429, 111552, 121665, 121686, 142199 and...

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Bibliographic Details
Published in:Annals of human genetics 2004-11, Vol.68 (6), p.536-545
Main Authors: Strange, R. C., El‐Genidy, N., Ramachandran, S., Lovatt, T. J., Fryer, A. A., Smith, A. G., Lear, J. T., Wong, C., Jones, P. W., Ichii‐Jones, F., Hoban, P. R.
Format: Article
Language:English
Subjects:
Aged
alleles
basal cell carcinoma
Carcinoma, Basal Cell - etiology
Carcinoma, Basal Cell - genetics
Exons
Genetic Predisposition to Disease
Haplotypes
Humans
Introns
Membrane Proteins - genetics
Patched Receptors
Patched-1 Receptor
Polymorphism, Genetic
PTCH
Receptors, Cell Surface
Skin Neoplasms - etiology
Skin Neoplasms - genetics
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Summary:Summary Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2318, 3429, 111552, 121665, 121686, 142199 and 233944 and intron 91336‐135 and 152560+9PTCH variants were sufficiently common for use in case‐control studies, and if selected markers were associated with risk. Intron 152560+9 and exon 233944 variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G2560+9‐C3944 haplotype was lower in all cases (odds ratio = 0.44, p = 0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.
ISSN:0003-4800
1469-1809
DOI:10.1046/j.1529-8817.2004.00132.x