GLI1 genotypes do not predict basal cell carcinoma risk: a case control study

Abstract

Background: Susceptibility to basal cell carcinoma results from complex interactions between ultraviolet radiation exposure and genetic factors. The GLI1 oncogene is believed to play a role in the genesis of these tumors. We determined whether GLI1 polymorphisms were risk factors for developing basal cell carcinoma, either alone or in combination with patterns of past sun exposure, and whether there were functional differences among different GLI1 haplotypes.

Results: GLI1 genotypes at c.2798 and c.3298 from 201 basal cell carcinoma patients were compared to 201 age and sex-matched controls. Neither genotype nor haplotype frequencies differed between cases and controls. However, the odds of developing basal cell carcinoma on the trunk compared to the head/neck appeared somewhat lower with carriers of the c.3298GC than the CC genotype. There was no evidence for interactions between skin type, childhood sunburning, average adult sun exposure, adult sunbathing, or intermittency of sun exposure and GLI1 haplotype. Additionally, we found no significant differences in transcription activation or cell transforming ability among the four GLI1 haplotypes.

Conclusion: These results suggest that different GLI1 genotypes alone or in combination with past sun exposure patterns as assessed in this study do not affect basal cell carcinoma risk.

Figure 1

Different GLI1 haplotypes function similarly. A. Different GLI1 haplotypes activate transcription of a CAT reporter comparably in HeLa cells. The GLI1 haplotypes are indicated along the abscissa with the amount transfected (ng) in each experiment. CAT activity, normalized by measuring β-galactosidase activity spectrophotometrically (Promega, Madison, WI), is indicated on the ordinate. Bars represent the means derived from three independent experiments. *indicates p < 0.05 calculated using a test of difference between means, comparing 2798G;3298G with the corresponding amount of each of the other haplotypes. B. Different GLI1 haplotypes transform RK3E cells comparably. The p value represents a test of difference between means, comparing 2798G;3298G with each of the other GLI1 haplotypes.