Karagas MR, McDonald JA, Greenberg ER, Stukel TA, Weiss JE, Baron JA, Stevens MM, et al.
Journal of the National Cancer Institute. Date of publication 1996 Dec 18;volume 88(24):1848-53.
1. J Natl Cancer Inst. 1996 Dec 18;88(24):1848-53.
Risk of basal cell and squamous cell skin cancers after ionizing radiation
therapy. For The Skin Cancer Prevention Study Group.
Karagas MR(1), McDonald JA, Greenberg ER, Stukel TA, Weiss JE, Baron JA, Stevens
MM.
Author information:
(1)Department of Community and Family Medicine, Dartmouth Medical School,
Hanover, NH 03755-3861, USA.
BACKGROUND: Human evidence that ionizing radiation is carcinogenic first came
from reports of nonmelanoma skin cancers (NMSCs) on the hands of workers using
early radiation devices. An increased risk of NMSC has been observed among
uranium miners, radiologists, and individuals treated with x rays in childhood
for tinea capitis (ringworm of the scalp) or for thymic enlargement; NMSC is one
of the cancers most strongly associated with the atomic bombing of Hiroshima and
Nagasaki. Although exposure to ionizing radiation is a known cause of NMSC, it is
not yet clear whether therapeutic radiation causes both major histologic types of
NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Additionally,
the potentially modifying effects, such as latency, age when treated, and type of
treatment, are not well understood.
PURPOSE: We investigated the relative risks of BCC and SCC associated with
previous radiation therapy and evaluated these risks in relation to age and time
since initial treatment and the medical condition for which radiation therapy was
given.
METHODS: The study group comprised individual diagnosed with at least one BCC or
SCC from January 1980 through February 1986, who were recruited to participate in
a skin cancer prevention trial designed to test whether oral beta-carotene
supplementation would reduce the risk of new NMSCs. Patients were identified
through the dermatology and pathology records of academic medical centers in
Hanover, NH; Los Angeles, CA; San Francisco, CA; and Minneapolis, MN. Each
participant completed a questionnaire detailing lifetime residence, pigmentary
characteristics, occupational and recreational sun exposure, and history of
radiation therapy. At enrollment, a study dermatologist assessed skin type
(tendency to burn or tan) and extent of actinic skin damage. Participants were
followed with an annual dermatologic examination for an average of 4 years. Of
the 5232 potentially eligible individuals, 1805 were enrolled in the trial. We
excluded 112 patients who reported previous radiation therapy for skin cancer
only and three with missing information on whether they were ever treated with
radiation therapy, leaving 1690 patients for the analysis. Approximately 4% of
the patients died or discontinued participation for other reasons during each
study year. We examined time to occurrence of first new histopathologically
confirmed BCC and SCC during the follow-up period in relation to history of
radiation therapy (for reasons other than NMSC) using a proportional hazards
model. A multiple end points survival model was used to compare the rate ratios
(RRs) for BCC and SCC. We also used a longitudinal method of analysis to compute
the RR of total new BCC and SCC tumors per person per study year associated with
radiation therapy. Using this method, we additionally assessed the potential
modifying effects of age at treatment, latency, and type of therapy. All P values
were derived from two-sided statistical tests of significance.
RESULTS: Among the participants we studied, 597 developed a new BCC (n = 1553
tumors) and 118 developed a new SCC (n = 179 tumors). The time to first new BCC,
but not SCC, was associated with prior radiation therapy (RR = 1.7; 95%
confidence interval [CI] = 1.4-2.0 and RR = 1.0; 95% CI = 0.6-1.7, respectively;
P = .03 for the difference between the RRs). The RR of total BCC tumors was
slightly higher (RR = 2.3; 95% CI = 1.7-3.1), but it was still unity for SCC (RR
= 1.0; 95% CI = 0.5-1.9). BCC risk appeared to increase with younger age at
exposure and time since initially treated, although these effects were only
marginally statistically significant (P for trend = .06 and .07, respectively).
Also, risk of BCC was more strongly related to treatment for acne (RR = 3.3; 95%
CI = 2.1-5.2) than other conditions.
CONCLUSIONS AND IMPLICATIONS: Our data suggest that exposure to therapeutic
radiation is associated with BCC but not with SCC.
PMID: 8961975 [Indexed for MEDLINE]
