AS242 - DNA Repair, Telomere Length, and Cutaneous Malignant Melanoma Risk
Investigator Names and Contact Information
Jiali Han, jiali.han@channing.harvard.edu
Introduction/Intent
Cancer of the skin (non-melanoma and melanoma skin cancers combined) is the most common form of cancer, accounting for more than 50% of all cancers. Most of the more than 1 million cases of skin cancer diagnosed yearly in the United States are considered to be sun-related. Melanoma, the most serious type of skin cancer, accounts for about 4% of cases of skin cancer but causes about 79% of deaths due to skin cancer. The number of new cases of melanoma in the US is rising dramatically 1. The American Cancer Society estimates that about 59,600 cases of invasive melanoma will be diagnosed in 2005 and that melanoma will account for most (about 7,800) of the 10,600 deaths due to skin cancer1.
As melanoma is becoming an increasingly serious public health problem in the US and globally, research on genetic susceptibility to melanoma is critical in identifying high-risk groups and providing individualized preventive strategies. However, it has been relatively understudied compared to other common cancers. Familial melanoma constitutes only 5-12% of total melanoma cases2, and only 20-40% of the observed familial clustering of melanoma is attributable to the strongly predisposing CDKN2A/p16 and CDK4 mutations3. Most of the genetic variants that contribute to the risk of developing sporadic melanoma remain unknown.
Telomere length in peripheral blood leukocytes (PBLs) has emerged as a potential biomarker of aging and of risk of age-related diseases such as cancers. Telomere length is determined in part by inherited genetic factors. In addition to causing DNA damage, UVB irradiation shortens telomeres. In skin tissue, telomere disruption triggers multiple DNA damage responses. We propose to examine telomere length and the genetic variants in telomere-related genes in relation to the risk of cutaneous malignant melanoma (hereafter called melanoma). We will include 586 incident cases of melanoma and 586 matched controls who provided blood samples pre-diagnostically from three large well-characterized cohorts, the Women’s Health Initiative Observational Study, the Nurses Health Study, and Nurses Health Study II.
Specific aims
1. To evaluate whether shorter telomere length in peripheral blood leukocytes is associated with increased risk of melanoma.
2. To evaluate whether genetic variants in telomere-related genes (TERT, POT1, TNKS, TRF1, TRF2, TINF2, and TRF2IP) are associated with the risk of melanoma.
3. To evaluate interactions between telomere length and inherited variants in telomere-related genes and tendency to burn/tan on melanoma risk.
Results/Findings
Some of the publications related to this ancillary study are:
Ms1163 - Nan H, Du M, De Vivo I, Manson JE, Liu S, McTiernan A, Curb JD, Lessin LS, Bonner MR, Guo Q, Qureshi AA, Hunter DJ, and Han J. Shorter telomeres associate with a reduced risk of melanoma development. Cancer Res. 2011 Oct 25. [Epub ahead of print]
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.
References
1. Cancer Facts and Figures. American Cancer Society 2005.
2. Goldstein AM, Tucker MA. Genetic epidemiology of cutaneous melanoma: a global perspective. Arch Dermatol 2001; 137:1493-6.
3. Kefford RF, Newton Bishop JA, Bergman W, Tucker MA. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol 1999; 17:3245-51.