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Genetic variants in telomere-maintaining genes and skin cancer risk

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Abstract

Telomere-related genes play an important role in maintaining the integrity of the telomeric structure that protects chromosome ends, and telomere dysfunction may lead to tumorigenesis. We evaluated the associations between 39 SNPs, including 38 tag-SNPs in telomere-related genes (TERT, TRF1, TRF2, TNKS2, and POT1) and one SNP (rs401681) in the TERT-CLPTM1L locus which has been identified as a susceptibility locus to skin cancer in the previous GWAS, and the risk of skin cancer in a case–control study of Caucasians nested within the Nurses’ Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. Of the 39 SNPs evaluated, ten showed a nominal significant association with the risk of at least one type of skin cancer. After correction for multiple testing within each gene, two SNPs in the TERT gene (rs2853676 and rs2242652) and one SNP in the TRF1 gene (rs2981096) showed significant associations with the risk of melanoma. Also, the SNP rs401681 in the TERT-CLPTM1L locus was replicated for the association with melanoma risk. The additive odds ratio (OR) [95% confidence interval (95% CI)] of these four SNPs (rs2853676[T], rs2242652[A], rs2981096[G], and rs401681[C]) for the risk of melanoma was 1.43 (1.14–1.81), 1.50 (1.14–1.98), 1.87 (1.19–2.91), and 0.73 (0.59–0.91), respectively. Moreover, we found that the rs401681[C] was associated with shorter relative telomere length (P for trend, 0.05). We did not observe significant associations for SCC or BCC risk. Our study provides evidence for the contribution of genetic variants in the telomere-maintaining genes to melanoma susceptibility.

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Abbreviations

SCC:

Squamous cell carcinoma

BCC:

Basal cell carcinoma

OR:

Odds ratio

CI:

Confidence interval

UV:

Ultraviolet

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Acknowledgments

We thank Dr. Hardeep Ranu and Ms. Pati Soule of the Dana-Farber/Harvard Cancer Center High-Throughput Polymorphism Detection Core for their laboratory assistance, and Ms. Carolyn Guo for her programming support. We are indebted to the participants in the Nurses’ Health Study for their dedication and commitment. This work was supported by National Institutes of Health research grants CA122838, CA133914, CA082838, and CA132190. JP was supported by NIH training grant 5T32 CA 09001.

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Authors and Affiliations

  1. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Hongmei Nan, Jennifer Prescott, Immaculata De Vivo & Jiali Han

  2. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

    Hongmei Nan, Abrar A. Qureshi, Jennifer Prescott, Immaculata De Vivo & Jiali Han

  3. Clinical Research Program, Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Abrar A. Qureshi & Jiali Han

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  1. Hongmei Nan
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  2. Abrar A. Qureshi
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Correspondence to Hongmei Nan.

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Nan, H., Qureshi, A.A., Prescott, J. et al. Genetic variants in telomere-maintaining genes and skin cancer risk. Hum Genet 129, 247–253 (2011). https://doi.org/10.1007/s00439-010-0921-5

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