A Community-Based Study of Nucleotide Excision Repair Polymorphisms in Relation to the Risk of Non-Melanoma Skin Cancer
Anthony J. Alberg, PhD, MPH
Blatt Ness Professor
Division of Biostatistics and Epidemiology, Department of Medicine
Associate Director for Cancer Prevention and Control
Medical University of South Carolina Charleston, SC USA
What are the main findings of the study?
This was a community-based epidemiologic study of common variants in nucleotide excision repair genes in relation to the risk of non-melanoma skin cancer.
Nucleotide excision repair is known to be important to non-melanoma skin cancer because this pathway is responsible for finding and removing the DNA damage caused by exposure to ultraviolet radiation, the major environmental cause of non-melanoma skin cancer.
Xeroderma pigmentosum (XP) is an example of an autosomal recessive disorder in which rare but highly penetrant mutations in the XP genes lead to 1000-fold elevated risk of non-melanoma skin cancer.
To test whether common, less penetrant variants might also be associated with susceptibility to non-melanoma skin cancer, we studied 221 single nucleotide polymorphisms (SNPs) in 26 nucleotide excision repair genes.
The prevalence of minor alleles was compared in 900 case with non-melanoma skin cancer who were individually matched to a control without any cancer history according to age, sex, and skin type. The study population was limited to those of European ancestry.
For the most part, the associations detected were specific to basal cell carcinoma of the skin and did not apply to squamous cell carcinoma of the skin.
The main study finding was that the three most significant SNPs associated with basal cell carcinoma of the skin were specific to the ERCC6 (Cockayne Syndrome B) gene.
Were any of the findings unexpected?
The strong signal from SNPs in ERCC6/CSB in relation to NMSC, and particularly with respect to BCC risk, had to our knowledge not been previously reported.
This is an interesting finding. We are not aware of previous studies that specifically interrogated the nucleotide excision repair pathway so thoroughly, which is perhaps why these associations had not been previously noted.
What should clinicians and patients take away from this study?
The finding from this study should be viewed as hypothesis-generating and will need to be replicated, so at the present time there are no implications for clinical practice.
These findings do raise the possibility that common variants in the ERCC6/CSB gene may be associated with susceptibility to basal cell carcinoma of the skin, findings that if replicated could in the long run lead to improved understanding of human skin carcinogenesis.
What recommendations do you have for dermatology health care providers as a result of your study?
These findings should be viewed as preliminary and are not directly relevant to clinical practice at the present time.
The primary strategy to prevent non-melanoma skin cancer is to protect the skin from exposure to solar ultraviolet radiation.
Results from our study and similar studies may in the long run help to characterize those who are most susceptible to skin cancer based on genetic profile.
A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer.
Wheless L, Kistner-Griffin E, Jorgensen TJ, Ruczinski I, Berthier-Schaad Y,
Kessing B, Hoffman-Bolton J, Francis L, Shugart YY, Strickland PT,
Kao WH, Alani RM, Smith MW, Alberg AJ.
Department of Medicine, Division of Epidemiology and Biostatistics, Medical University of South Carolina, Charleston, South Carolina, USA.
J Invest Dermatol. 2012 May;132(5):1354-62. doi: 10.1038/jid.2012.4.
Epub 2012 Feb 16.