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

Timothy J Jorgensen, Ingo Ruczinski, Yin Yao Shugart, Lee Wheless, Yvette Berthier Schaad, Bailey Kessing, Judith Hoffman-Bolton, Kathy J. Helzlsouer, Wen-Hong Linda Kao, Lesley Francis, Rhoda M. Alani, Paul T. Strickland, Michael W. Smith, Anthony J. Alberg

Research output: Contribution to journalArticle

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= 2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n= 2349); (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.

Original languageEnglish (US)
Pages (from-to)e288-e293
JournalCancer Epidemiology
Volume36
Issue number5
DOIs
StatePublished - Oct 1 2012

Keywords

  • Fas
  • Genetics
  • Hedgehog
  • Polymorphisms
  • Skin cancer
  • Vitamin D receptor

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research

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    Jorgensen, T. J., Ruczinski, I., Yao Shugart, Y., Wheless, L., Berthier Schaad, Y., Kessing, B., Hoffman-Bolton, J., Helzlsouer, K. J., Kao, W-H. L., Francis, L., Alani, R. M., Strickland, P. T., Smith, M. W., & Alberg, A. J. (2012). A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer. Cancer Epidemiology, 36(5), e288-e293. https://doi.org/10.1016/j.canep.2012.05.001