Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
Centers for Disease Control and Prevention CDC Home Search CDC CDC Health Topics A-Z    
Office of Genomics and Disease Prevention  
Office of Genomics and Disease Prevention
e-Journal Club

XRCC1 Arg399Gln Polymorphism, Sunburn, and Non-melanoma Skin Cancer: Evidence of Gene-Environment Interaction

May 1, 2002

Reviewed by:

Caroline Hoffman, MSPH (candidate)
Department of Epidemiology
Rollins School of Public Health
Emory University

The Health Outcome

Non-melanoma Skin Cancer (NMSC) is a malignant growth of the epithelial layer of the skin.  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common forms of NMSC.  BCC is more common than SCC, but SCC is more invasive and may account for about three-fourths of all deaths from NMSC (2).  Research studies have identified several exposures that are associated with NMSC, including UV radiation, ionizing radiation (3,4), and arsenic (5,6).  However, host susceptibility factors such as skin pigmentation and tendency to burn are also related to NMSC (7,8).  DNA repair capability has been linked to skin cancer, but the precise genes that contribute to this relationship are unknown (9).

The Finding

Nelson HH et al conducted a case-control study consisting of 499 BCC cases, 246 SCC cases, and 431 controls in New Hampshire to investigate the relation between the XRCC1 arg399gln polymorphism and its interaction with carcinogen exposure and non-melanoma skin cancer.  Cases were identified by an incidence survey of all newly diagnosed cases of BCC and SCC in New Hampshire between July 1993 and June 1995.  Controls were derived from the New Hampshire Department of Transportation and the Healthcare Financing Administration enrollment list and were frequency matched to cases by gender and age.

Two primary exposures were considered for analysis: sunburn history and therapeutic ionizing radiation.  Results from a questionnaire administered by the researchers during an in-home interview provided information on exposures.  Sunburn exposure was defined as the number of painful sunburns lasting ≥ two days and was dichotomized into low exposure (0 to 2 painful sunburns) and high exposure (≥ three painful sunburns) based on the median number of sunburns among control subjects.  Self-report of therapeutic ionizing radiation was verified in 76% of subjects, and radiation therapy to treat NMSC was excluded from the analysis.

Overall, the XRCC1 gln399gln homozygote variant genotype was significantly associated with a decreased risk of both BCC [odds ratio (OR) = 0.7 (95% confidence interval (CI) 0.4-1.0)] and SCC [OR = 0.6 (95% CI 0.3-0.9)].  However, among individuals with the homozygote variant genotype who had experienced ≥ 3 painful sunburns, there was an increased relative risk of SCC [OR = 6.8 (95% CI 2.4-19.2)].  There was no significant interaction found between ionizing radiation therapy and NMSC or between sunburn and BCC.

Public Health Implications

Between 1979 and 1993, the incidence rate of BCC increased 80% and the incidence rate of SCC increased more than 230% (1).  Because rates of NMSC have increased so dramatically, it is of public health importance to better understand what factors contribute to BCC and SCC and to understand how these factors interact.  By increasing our knowledge of the environmental exposures and genetic determinates that lead to NMSC, we can identify those persons at risk and more effectively implement interventions and health education programs.

References

  1. Nelson HH, et al.  The XRCC1 arg399gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. Cancer Res 2002;62(1):152-5.
  2. Dunn JE, et al. Skin cancer as a cause of death. California Med. 1965;102:361-3.
  3. Weinstock , MA . National skin cancer prevention program: at a glance 1996. Washington D.C. : National Public Health Service.
  4. Kargas M, et al.  Increase in Incidence rates of basal cell and squamous cell skin cancer in New Hampshire , USA . New Hampshire Skin Cancer Study Group. Int. J. Cancer. 1999, 81: 555-559.
  5. Litcher M, et al.  Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma. The New Hampshire Skin Cancer Study Group. Arch Dermatol 2000;136:1007-111.
  6. Kargas M, et al.  Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study. Am J Epidemiol 2001;153:559-565.
  7. Kargas M, et al.  A dose-response analysis of skin cancer inorganic arsenic in drinking water. Risk Anal 1989;9:519-28.
  8. Gallagher R, et al.  Sunlight exposure, pigmentary factors, and risk of nonmelanomcytic skin cancer I. Squamous cell carcinoma. Arch Dermatol 1995;31:164-9.
  9. Gallagher R, et al.  Sunlight exposure, pigmentary factors, and risk of nonmelanomcytic skin cancer II. Basal cell carcinoma. Arch Dermatol 1995;131:157-63.
  10. Wei Q, et al.  DNA repair and susceptibility to basal cell carcinoma: a case-control study. Am J Epidemiol 1994;140:568-607.
  11. E-journal club abstraction template
Last Updated August 27, 2004