Karagas M R, McDonald J A, Greenberg E R, Stukel T A, Weiss J E, Baron J A, Stevens M M
Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH 03755-3861, USA.
J Natl Cancer Inst. 1996 Dec 18;88(24):1848-53. doi: 10.1093/jnci/88.24.1848.
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.
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.
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.
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.
Our data suggest that exposure to therapeutic radiation is associated with BCC but not with SCC.
电离辐射具有致癌性的人体证据最初来自于使用早期辐射设备的工人手部非黑色素瘤皮肤癌（NMSC）的报告。在铀矿工人、放射科医生以及童年时期因头癣（头皮癣）或胸腺肿大接受过X射线治疗的个体中，已观察到NMSC风险增加；NMSC是与广岛和长崎原子弹爆炸关联最为紧密的癌症之一。尽管暴露于电离辐射是已知的NMSC病因，但尚不清楚治疗性辐射是否会导致NMSC的两种主要组织学类型，即基底细胞癌（BCC）和鳞状细胞癌（SCC）。此外，诸如潜伏期、治疗时的年龄以及治疗类型等潜在的影响因素还未得到充分了解。
我们调查了既往放疗与BCC和SCC的相对风险，并根据年龄、首次治疗后的时间以及放疗所针对的疾病状况评估了这些风险。
研究组包括1980年1月至1986年2月期间被诊断患有至少1例BCC或SCC的个体，他们被招募参加一项皮肤癌预防试验，旨在测试口服β-胡萝卜素补充剂是否会降低新发NMSC的风险。通过新罕布什尔州汉诺威、加利福尼亚州洛杉矶、加利福尼亚州旧金山以及明尼苏达州明尼阿波利斯的学术医疗中心的皮肤科和病理记录识别患者。每位参与者填写一份问卷，详细说明终生居住情况、色素沉着特征、职业和娱乐性阳光暴露以及放疗史。在入组时，研究皮肤科医生评估皮肤类型（晒伤或晒黑倾向）和光化性皮肤损伤程度。参与者每年接受一次皮肤科检查，平均随访4年。在5232名潜在符合条件的个体中，1805人参加了试验。我们排除了仅报告既往因皮肤癌接受过放疗的112名患者以及3名缺失是否接受过放疗信息的患者，剩余1690名患者用于分析。在每个研究年度，约4%的患者因其他原因死亡或退出研究。我们使用比例风险模型，研究随访期间首次经组织病理学确诊的新BCC和SCC的发生时间与放疗史（因NMSC以外的原因）的关系。使用多终点生存模型比较BCC和SCC的率比（RR）。我们还使用纵向分析方法计算与放疗相关的每人每年新发BCC和SCC肿瘤总数的RR。使用这种方法，我们还评估了治疗时年龄、潜伏期和治疗类型的潜在影响。所有P值均来自双侧显著性统计检验。
在我们研究的参与者中，597人发生了新的BCC（n = 1553个肿瘤），118人发生了新的SCC（n = 179个肿瘤）。首次出现新BCC的时间与既往放疗相关，但SCC并非如此（RR分别为1.7；95%置信区间[CI] = 1.4 - 2.0和RR = 1.0；95% CI = 0.6 - 1.7；RR之间的差异P = .03）。BCC肿瘤总数的RR略高（RR = 2.3；95% CI = 1.7 - 3.1），但SCC的RR仍为1.0（RR = 1.0；95% CI = 0.5 - 1.9）。BCC风险似乎随着暴露时年龄较小以及首次治疗后的时间增加而升高，尽管这些影响在统计学上仅具有微弱的显著性（趋势P值分别为.06和.07）。此外，与其他疾病相比，BCC风险与痤疮治疗的相关性更强（RR = 3.3；95% CI = 2.1 - 5.2）。
我们的数据表明，暴露于治疗性辐射与BCC相关，但与SCC无关。
