Second Malignancies in Patients with Skin Cancer
Second Malignancies in Patients with Skin Cancer
Abstract & Commentary
By William B. Ershler, MD
Synopsis: A prospective analysis of an established epidemiological cohort indicated a significant risk of developing subsequent malignancy among those with compared to those without established non-melanoma skin cancers. The increased risk was apparent even after adjustment for confounding variables such as age, sex, smoking history, socioeconomic status, and sun exposure.
Source: Chen J, et al. Nonmelanoma skin cancer and risk for subsequent malignancy. J Natl Cancer Inst. 2008;100:1215-1222.
Several studies1-4 have suggested that individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies, but most were derived from tumor registries, and key variables were often not available. Thus, Chen et al capitalized on the well characterized CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort to conduct a community-based, prospective cohort study to address whether a history of NMSC is a risk factor for subsequent malignancy.
The CLUE II cohort was established in Washington County, MD, in 1989, and consisted of 32,894 participants, of which 19,174 were analyzed in the current study. Criteria included age 25 years or older, residency in Washington County, and availability of key data (age, sex, socioeconomic status, medical illnesses, etc.). From this, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18,405) a personal history of NMSC during a 16-year follow-up period. For all those who reported a history of NMSC, pathological confirmation was 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.
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 (RR = 1.99, 95% CI = 1.70 to 2.33), other than NMSC, 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).
Commentary
Thus, Chen et al present data from a community-based, prospective cohort study demonstrating solid evidence for an association between a NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors. It is important to highlight that the association was true for both squamous and basal cell carcinomas, and that the risk was greater for those who experienced NMSC at a younger age. The size of the study population, its prospective design, duration of follow-up (16 years), appropriate adjustments for other risk factors, such as sun exposure, cigarette smoking, and socioeconomic status, and confirmation of all self-reported cancer diagnoses provide confidence of the validity of the observations and conclusions.
NMSC is common, with more than one million patients diagnosed each year in the United States.5 Although not a disease associated with high mortality, it is a major cause of morbidity and medical expenditure. Now, it's apparent that the presence of NMSC is an indicator of increased risk of subsequent development of non-skin cancer malignancies, and clinicians, particularly those in primary care, may chose to increase their level of surveillance accordingly. This, it would seem, would be particularly true for younger patients with NMSC, for whom the risk of second malignancy appears greater.
The observation that NMSC is associated with a higher risk of a wide range of cancers (lung, colon, breast) suggests that a basic underlying mechanism, such as impaired DNA repair, may render certain individuals susceptible to malignancy at multiple sites. Alternatively, whatever immunological forces capable of identifying and destroying tumor cells may vary among individuals and account for the observation. From the perspective of a clinical oncologist, this is the type of epidemiological observation that warrants a return to the laboratory. What is it that makes a person susceptible to multiple malignancies?
References
1. Frisch M, et al. Risk for subsequent cancer after diagnosis of basal-cell carcinoma. A population-based, epidemiologic study. Ann Intern Med. 1996;125:815-821.
2. Milan T, et al. Subsequent primary cancers after basal-cell carcinoma: A nationwide study in Finland from 1953 to 1995. Int J Cancer. 2000;87:283-288.
3. Wassberg C, et al. Second primary cancers in patients with squamous cell carcinoma of the skin: a population-based study in Sweden. Int J Cancer. 1999;80: 511-515.
4. Kahn HS, et al. Increased cancer mortality following a history of nonmelanoma skin cancer. JAMA. 1998; 280:910-912.
5. Jemal A, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43-66.
A prospective analysis of an established epidemiological cohort indicated a significant risk of developing subsequent malignancy among those with compared to those without established non-melanoma skin cancers. The increased risk was apparent even after adjustment for confounding variables such as age, sex, smoking history, socioeconomic status, and sun exposure.Subscribe Now for Access
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