TY - JOUR
T1 - A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer
AU - Jsorgensen, Timothy J.
AU - Ruczinski, Ingo
AU - Yao Shugart, Yin
AU - Wheless, Lee
AU - Berthier Schaad, Yvette
AU - Kessing, Bailey
AU - Hoffman-Bolton, Judith
AU - Helzlsouer, Kathy J.
AU - Kao, W. H.Linda
AU - Francis, Lesley
AU - Alani, Rhoda M.
AU - Strickland, Paul T.
AU - Smith, Michael W.
AU - Alberg, Anthony J.
N1 - Funding Information:
Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, which is funded by the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the CDC to make the cancer registry data available.
Funding Information:
This work was supported by the National Cancer Institute (NCI) (R01 CA105069, HHSN26120080001E) and the Intramural Research Program of the NCI, Center for Cancer Research . This publication does not necessarily reflect the views or policies of the NCI, NIMH, NIH, U.S. DHHS, the U.S. government, or the Maryland Cancer Registry, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Fas
KW - Genetics
KW - Hedgehog
KW - Polymorphisms
KW - Skin cancer
KW - Vitamin D receptor
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U2 - 10.1016/j.canep.2012.05.001
DO - 10.1016/j.canep.2012.05.001
M3 - Article
C2 - 22677152
AN - SCOPUS:84865863540
SN - 1877-7821
VL - 36
SP - e288-e293
JO - Cancer Epidemiology
JF - Cancer Epidemiology
IS - 5
ER -