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Open Access 01-12-2009 | Research

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

Authors: Andrea Watson, Paul Kent, Murad Alam, Amy S Paller, David M Umbach, Joon Won Yoon, Philip M Iannaccone, David O Walterhouse

Published in: Molecular Cancer | Issue 1/2009

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.

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Armstrong BK, Kricker A: The epidemiology of UV induced skin cancer. J Photochem Photobiol B. 2001, 63: 8-18. 10.1016/S1011-1344(01)00198-1CrossRefPubMed

Lear JT, Smith AG, Bowers B, Heagearty AH, Jones PW, Gilford J, Alldersea J, Strange RC, Fryer AA: Truncal tumor site is associated with high risk of multiple basal cell carcinoma and is influenced by glutathione S-transferase, GSTT1, and cytochrome P459, CYP1A1 genotypes, and their interaction. J Invest Dermatol. 1997, 108: 519-522. 10.1111/1523-1747.ep12289738CrossRefPubMed

Liboutet M, Portela M, Delestaing G, Vilmer C, Dupin N, Gorin I, Saiag P, Lebbe C, Kerob D, Dubertret L, Grandchamp B, Basset-Sequin N, Soufir N: MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas. J Invest Dermatol. 2006, 126: 1510-1517. 10.1038/sj.jid.5700263CrossRefPubMed

Gudbjartsson DF, Sulem P, Stacey SN, Goldstein AM, Rafnar TH, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Sveinsdottir SG, Magnusson V, Lindblom A, Kostulas K, Botella-Estrada R, Soriano V, Juberias P, Grasa M, Saez B, Andres R, Scherer D, Rudnai P, Gurzau E, Koppova K, Kiemeney LA, Jakobsdottir M, Steinberg S, Helgason A, Gretarsdottir S, Tucker MA, Mayordomo JI, Nagore E, Kumar R, Hansson J, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet. 2008, 70: 886-891. 10.1038/ng.161. 10.1038/ng.161CrossRef

Scherer D, Bermejo JL, Rudnai P, Gurzau E, Koppova K, Hemminki K, Kumar R: MC1R variants associated susceptibility to basal cell carcinoma of skin: Interaction with host factors and XRCC3 polymorphism. Int J Cancer. 2008, 122: 1787-1793. 10.1002/ijc.23257CrossRefPubMed

Gailani MR, Stahle-Backdahl M, Lefell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE, Toftgard R: The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet. 1996, 14: 78-81. 10.1038/ng0996-78CrossRefPubMed

Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH, de Sauvage FJ: Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998, 391: 90-92. 10.1038/34201CrossRefPubMed

Dahmane N, Lee J, Robbins P, Heller P, Ruiz i Altaba A: Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature. 1997, 389: 876-881. 10.1038/39918CrossRefPubMed

Nilsson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, Toftgard R: Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc Natl Acad Sci USA. 2000, 97: 3438-3443. 10.1073/pnas.050467397PubMedCentralCrossRefPubMed

10.

Wang XQ, Chan N, Rothnagel JA: Letters to the editor: identification of polymorphic variants of the GLI1 oncogene. J Invest Dermatol. 2000, 115: 328-329. 10.1046/j.1523-1747.2000.00065.xCrossRefPubMed

11.

Qiu GR, Gong LG, He G, Xu XY, Xin N, Sun GF, Yuan YH, Sun KL: Association of the GLI gene with ventricular septal defect after the susceptibility gene being narrowed to 3.56 cM in 12q13. Chin Med J. 2006, 119: 267-274.PubMed

12.

Yoon JW, Liu CZ, Yang JT, Swart R, Iannaccone P, Walterhouse D: GLI Activates Transcription through a herpes Simplex Viral Protein 16-Like Activation Domain. J Biol Chem. 1998, 273: 3496-3501. 10.1074/jbc.273.6.3496CrossRefPubMed

13.

Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988, 124 (6): 869-71. 10.1001/archderm.124.6.869CrossRefPubMed

14.

Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN: Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis. 2000, 36: 167-176. 10.1053/ajkd.2000.8290CrossRefPubMed

15.

Luscombe CJ, Fryer AA, French ME, Liu S, Saxby MF, Jones PW, Strange RC: Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet. 2001, 358: 641-642. 10.1016/S0140-6736(01)05788-9CrossRefPubMed

16.

Lovatt TJ, Lear JT, Bastrilles J, Wong C, Griffiths CE, Ramachandran S, Smith AG, Salim A, Fryer AA, Jones PW, Strange RC: Associations between UVR exposure and basal cell carcinoma site and histology. Cancer Lett. 2004, 216: 191-197. 10.1016/j.canlet.2004.08.008CrossRefPubMed

17.

Lovatt TJ, Lear JT, Bastrilles J, Wong C, Griffiths CE, Samarasinghe V, Roebuck J, Ramachandran S, Smith AG, Jones PW, Fryer AA, Strange RC: Associations between ultraviolet radiation, basal cell carcinoma site and histology, host characteristics, and rate of development of further tumors. J Am Acad Dermatol. 2005, 52: 468-473. 10.1016/j.jaad.2004.08.060CrossRefPubMed

18.

Ruppert JM, Vogelstein B, Kinzler KW: The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol Cell Biol. 1991, 11: 1724-1728.PubMedCentralPubMed

19.

Weir BS: Genetic Data Analysis II: methods for discrete population genetic data. 1996, Sunderland MA: Sinauer

Title: GLI1 genotypes do not predict basal cell carcinoma risk: a case control study
Authors: Andrea Watson
Paul Kent
Murad Alam
Amy S Paller
David M Umbach
Joon Won Yoon
Philip M Iannaccone
David O Walterhouse
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2009
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-8-113

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Abstract

Background

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