Susceptibility to Basal Cell Carcinoma: Associations with PTCH Polymorphisms

Abstract

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 9^1336‐135 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.