Radiation-related risk of basal cell carcinoma: a report from the Childhood Cancer Survivor Study

Abstract

Background: Basal cell carcinoma (BCC) is the most common malignancy in the United States. Ionizing radiation is an established risk factor in certain populations, including cancer survivors. We quantified the association between ionizing radiation dose and the risk of BCC in childhood cancer survivors.

Methods: Participants in the Childhood Cancer Survivor Study who reported a BCC (case subjects, n = 199) were matched on age and length of follow-up to three study participants who had not developed a BCC (control subjects, n = 597). The radiation-absorbed dose (in Gy) to the BCC location was calculated based on individual radiotherapy records using a custom-designed dosimetry program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and treatment factors, therapeutic radiation dose, and surrogate markers of sun sensitivity (skin and hair color) and the risk of BCC. A linear dose-response model was fitted to evaluate the excess odds ratio per Gy of radiation dose.

Results: Among case subjects, 83% developed BCC between the ages of 20 and 39 years. Radiation therapy, either alone or in combination with chemotherapy, was associated with an increased risk of BCC compared with no chemotherapy or radiation. The odds ratio for subjects who received 35 Gy or more to the skin site vs no radiation therapy was 39.8 (95% CI = 8.6 to 185). Results were consistent with a linear dose-response relationship, with an excess odds ratio per Gy of 1.09 (95% CI = 0.49 to 2.64). No other treatment variables were statistically significantly associated with an increased risk of BCC.

Conclusions: Radiation doses to the skin of more than 1 Gy are associated with an increased risk of BCC.

Figure 1.

Dose–response models for ionizing radiation to the skin surface. Black circles represent odds ratios from categorical model (error bars represent 95% confidence intervals) for the median dose for the category; median (category): 0.14 Gy (0.01–0.9 Gy), 2.6 Gy (1.0–4.9 Gy), 10.3 Gy (5.0–14.9 Gy), 19.2 Gy (15.0–24.9 Gy), 28.4 Gy (25.0–34.9 Gy), and 40.6 Gy (35.0–63.3 Gy). Linear model: relative risk = 1 + 1.09 × dose; linear exponential: relative risk = 1 + 1.32 × dose × exp(−0.0114 × dose). The horizontal dashed line corresponds to a relative risk of 1.0.