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Nonmelanoma Skin Cancer Increases Risk for Subsequent Cancers

August 28, 2008 — Individuals with a history of nonmelanoma skin cancer (NMSC) are at increased risk for subsequent noncutaneous cancers. The results of a study published in the August 26 Advance Access issue of the Journal of the National Cancer Institute showed that even after adjusting for other risk factors, a history of confirmed NMSC was associated with a statistically significantly increased risk for future noncutaneous malignant tumors and may be a marker of a general high-cancer risk phenotype.
The researchers found that the crude incidence rate of subsequent cancers other than NMSC was 293.5 cases per 10,000 person-years for those with a history of basal cell carcinoma and squamous cell carcinoma. This was in comparison with 77.8 per 10,000, among persons without a history of NMSC. The association remained robust even after the data was adjusted for potential confounders.
"Nonmelanoma skin cancer has been linked to suboptimal DNA repair capacity," said senior author Anthony Alberg, PhD, associate director of Cancer Prevention and Control at the Hollings Cancer Center, Medical University of South Carolina in Charleston. "If that's true, suboptimal DNA repair may explain the risk seen in other organs."
Suboptimal immune responses have also been associated with NMSC, explained Dr. Alberg, and some hypotheses have linked a systemic suboptimal inflammatory and/or immune response to carcinogenesis in general. Thus, it is possible that exposure to ultraviolet radiation, the major environmental cause of NMSC, may cause changes in normal tissue by inducing immune suppression in the skin, which then might compromise normal immune surveillance against nascent tumor cells.
Previous studies have suggested an association between a history of NMSC and the development of subsequent noncutaneous cancers. However, the majority of previous reports have been based on cancer registry data, without making adjustments for potential confounding lifestyle factors. The goal of the current investigation was to examine if a previous NMSC diagnosis was associated with an increased incidence of subsequent cancer, with use of a community-based prospective cohort study design. This methodology would allow for follow-up on an individual level as well as the ability to adjust for confounding variables.
Baseline data were collected from May 1, 1989, through November 30, 1989, from a cohort of 19,174 individuals. Of this group, 769 participants had a confirmed diagnosis of NMSC: 513 (67%) with basal cell carcinoma, 165 (21%) with squamous cell carcinoma, 60 (8%) with a diagnosis of both basal cell carcinoma and squamous cell carcinoma, and 31 (4%) with an unknown subtype.
The follow-up period lasted for 16 years, and the outcome of the study was the occurrence of a first confirmed primary cancer, aside from NMSC, that was diagnosed from January 1, 1990, through December 31, 2005.
When the data was adjusted for age, the risk for the development of a subsequent noncutaneous cancer was statistically significantly associated with a personal history of confirmed NMSC (relative risk [RR], 2.04). Adjustments made for factors such as sex, body mass index, cigarette smoking, and educational status barely altered the association (RR, 1.99). Even after adjusting for sunburn history and skin type, the association remained strong (RR, 1.98).
"We did not incorporate the family history, or other factors," Dr. Alberg told Medscape Oncology. "This is an interim study and we hope to look at genetic variances in the future."
The strongest association between a history of NMSC and subsequent cancers was observed in younger individuals (aged 25 - 44 years). The earlier age of NMSC diagnosis being strongly linked to the risk for the development of subsequent cancers is consistent with the pattern that might be expected for a marker of inherited predisposition to cancer, they noted.
The most frequently diagnosed cancers in the study population were similar to those that occur most commonly in the general population, such as lung, colorectal, breast, and prostate cancers. Statistical power was too limited to evaluate the association between NMSC and the risk for specific cancers, but the researchers were able to perform an analysis for cancer sites with more than 10 patients in the NMSC group.

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