July 27, 2012 — The most important risk factor for the development of basal cell carcinoma (BCC) is a prior history of the disease, according to an analysis of data from a study of more than 1100 people at high risk for the disease.
In addition, for the first time, a history of eczema has been linked to the disease.
Martin Weinstock, MD, professor of dermatology at Brown University and a clinician at the Veterans Affairs Medical Center in Providence, Rhode Island, and colleagues authored the study, which was published online July 19 in theJournal of Investigative Dermatology.
"Predictors of new BCCs on the face and ears among those at very high risk have not been studied in detail," the authors note.
"In an attempt to better define risk factors for future BCCs in an important high-risk group, we studied predictors of BCCs among individuals who had at least two prior keratinocyte carcinomas (KCs) who participated in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial."
That trial randomly assigned 1131 US military veterans, 97% of whom were men, to prophylactic treatment against BCC with either topical tretinoin or a topical placebo vehicle. Participants were also provided with sun protection factor 15 or greater sunscreen and were encouraged to use it during the study. Every 6 months, participants were examined by a study dermatologist.
Participants in the study tended to have heavily sun-damaged skin and, on average, 3.6 KCs during the 5 years preceding entry into the study.
Dr. Weinstock chaired this multicenter trial, which concluded last year, after a median follow-up of 3.6 years, but the results were disappointing: treatment with tretinoin failed to prevent recurrence of BCC in high-risk patients.
However, to further mine data from the study, Dr. Weinstock and colleagues conducted the current analysis to see what risk factors most influenced development of BCC in this group.
They report that 44% of the participants developed new BCCs during the follow-up period. Kaplan-Meir estimates for the development of new BCCs were 18% at 1 year, 42% at 3 years, and 55% at 5 years.
According to univariate analyses of the data, the authors say the most important predictor of new BCCs was prior BCCs. Participants with a history of more than 5 BCCs before entry into the study were more than 4 times as likely to develop another BCC than participants who had been diagnosed with 1 or no prior BCCs.
"The hazard rate ratio (HRR) of those with >5 BCCs in the past 5 years, compared with those with <2, was 4.01 (95% confidence interval (CI) 3.02–5.31)," the authors write.
Age was also a predictor of future BCCs, they say, with HRRs per decade being 1.26 (95% CI, 1.14 - 1.40). Sun sensitivity was another key factor for predicting future BCCs, with an HRR of 1.80 (95% CI, 1.16 - 2.80).
In addition, "[p]atient education level was negatively correlated with time to first BCC (HRR=0.73, 95% CI 0.61–0.88) for those who had completed any education beyond high school compared with those with less education," the authors write.
The authors especially highlighted another first-time finding, that a history of eczema was a significant risk factor for the development of BCCs. "History of eczema, as determined by participants' report of ever being told by a doctor that they had eczema, was also an independent risk factor for future BCCs (HRR=1.52, 95% CI 1.01–2.29)," they write. Of note, "[n]one of the 52 patients with a history of eczema had used the calcineurin inhibitors tacrolimus or pimicrolimus, based on examination of their medical records."
In addition, the authors emphasize, recent sunscreen use had little effect on the development of BCCs. In other words, damaging exposure earlier in life seemed to be far more important than recent exposure. That finding mirrors previous research.
"Although the conclusions from this one study cannot be definitive, we found no effect of sunscreen use or even sun exposure in recent decades on BCC risk, which underscores the importance of potential chemopreventive approaches to reducing the burden of disease in this population," the researchers conclude.
Study limitations include reliance on self-report and the potential for recall bias; lack of generalizability, as the populations studied were all veterans and almost entirely men; and restriction of skin areas studied to face and ears, lending to the possibility that risk factors for BCC in other skin regions may be different.
The US Department of Veterans Affairs Co-operative Studies Program funds this research. The authors have disclosed no relevant financial relationships.
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