A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer

Abstract

Introduction A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC. Methods The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n=2,296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: 1) Other (non-BCC) cancer only (n=2,349); 2) BCC only (n=534); and 3) BCC plus other cancer (n=446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway. Results Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05–1.82; p-value=0.02]. Conclusion The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype.

Association between genetic variation within vitamin D receptor‐DNA binding sites and risk of basal cell carcinoma

“…Vitamin D levels have been reported to be associated with incidence and outcomes of certain types of cancer, including NMSC . In addition, some studies have shown relationships between VDR gene polymorphisms and the risk of BCC . In addition, vitamin D‐binding protein (VDBP) single‐nucleotide polymorphisms (SNPs) affect 25(OH)D levels, thereby influencing skin carcinogenesis .…”

“…14,15 In addition, some studies have shown relationships between VDR gene polymorphisms and the risk of BCC. [16][17][18][19] In addition, vitamin D-binding protein (VDBP) single-nucleotide polymorphisms (SNPs) affect 25(OH)D levels, thereby influencing skin carcinogenesis. 15 Recently, genetic variations within VDR binding sites have emerged as important contributors to transcription factor affinity, and therefore, their impact on the function of VDES has begun to be considered.…”

Different Protein Expressions between Peripheral Ameloblastoma and Oral Basal Cell Carcinoma Occurred at the Same Mandibular Molar Area

“…These findings suggest that the pathogenesis of ameloblastoma is related to that of the OBCC. 18 , 19 , 20…”

Vitamin D and Skin Cancer

“…No significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. Thus, hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer‐prone phenotype . In a German study, associations indicated that the Apa1 and Taq1 genotypes may be important for development of BCCs, but not for SCCs.…”