Journal of the National Cancer Institute Advance Access published online on August 26, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn260
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© The Author 2008. Published by Oxford University Press.
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Nonmelanoma Skin Cancer and Risk for Subsequent Malignancy
Affiliations of authors: Division of Cancer Prevention, National Cancer Institute, Rockville, MD (JC); Department of Biostatistics (IR), Department of Epidemiology (TJJ, GY, YY, SCH, JH-B, KJH, AJA), and Department of Environmental Health Sciences (PTS), The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC (TJJ); Department of Oncology (RA) and Department of Dermatology (RA, NJL), The Johns Hopkins University School of Medicine, Baltimore, MD; George W. Comstock Center for Public Health Research and Prevention, Washington County, MD (SCH, JH-B, KJH, AJA); Mercy Medical Center, Baltimore, MD (KJH); Department of Biostatistics, Bioinformatics, and Epidemiology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (AJA)
Correspondence to: Anthony J. Alberg, Department of Biostatics, Bioinformatics, and Epidemiology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, PO Box 250955, Charleston, SC 29425 (e-mail: alberg{at}musc.edu).
Background: Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study.
Methods: In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18 405) a personal history of NMSC (total n = 19 174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided.
Results: The crude incidence rate (per 10 000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups (P for interaction = .022).
Conclusions: This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors.
| Context and Caveats Prior knowledge Prior studies have suggested that people with a personal history of nonmelanoma skin cancer (NMSC) have an increased risk of subsequent noncutaneous malignancies. However, the study designs made clear conclusions difficult. Study design Community-based prospective cohort study of the association of a personal history of NMSC with subsequent cancers, compared with no such history. Follow-up was 16 years. Contribution The crude incidence rate of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 per 10 000 person-years and with a negative history was 77.8 per 10 000 person-years. Persons with a personal history of NMSC had a statistically significantly higher adjusted risk of being diagnosed with a subsequent cancer other than NMSC than those without such a history. The association was observed for both basal and squamous cell carcinomas, and it was robust even after adjusting for potential confounding variables and accounting for sun exposure. Implications NMSC appears to be a clinically important and substantial risk marker for subsequent malignancies and may be a marker of a general high–cancer risk phenotype. Additional research on this association is thus warranted. Limitations Persons with a personal history of NMSC may have been more likely than those without such history to receive regular medical care that would enhance the likelihood of cancer detection. The cohort studied was established in a single county and so may not be representative of the total population. Adjustments for skin type and sunburn history were imputed for a large proportion of missing data. Uncertainty in the imputation could introduce uncertainty into the results. From the Editors
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Manuscript received November 27, 2007; revised June 4, 2008; accepted June 30, 2008.
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