Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy
Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy
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DOI：
10.1093/jnci/88.24.1848
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发表时间：
1996-12-18
期刊：
影响因子：
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通讯作者：
Stevens, M
中科院分区：
文献类型：
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作者：
Karagas, MR;McDonald, JA;Stevens, M
背景：电离辐射致癌的人类证据首先来自使用早期辐射设备的工人手上的非黑色素瘤皮肤癌（NMSCs）的报道。在铀矿工人、放射科医生和儿童时期因头癣（头皮癣）或胸腺肿大而接受x射线治疗的个体中观察到NMSC的风险增加；NMSC是与广岛和长崎原子弹爆炸最密切相关的癌症之一。虽然暴露于电离辐射是NMSC的已知原因，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，基底细胞癌（BCC）和鳞状细胞癌（SCC）。此外，潜在的修饰效应，如潜伏期、治疗时的年龄和治疗类型，还不是很清楚。目的：我们调查了与既往放射治疗相关的BCC和SCC的相对风险，并评估了这些风险与初始治疗后的年龄和时间以及给予放射治疗的医疗状况的关系。方法：研究组包括从1980年1月到1986年2月被诊断为至少一种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NMSCs的风险。通过汉诺威学术医疗中心的皮肤病学和病理学记录确定患者；洛杉矶，加州；加州旧金山；以及明尼苏达州的明尼阿波利斯。每个参与者都完成了一份问卷，详细说明了一生的居住情况、色素特征、职业和娱乐阳光照射以及放射治疗史。在入组时，一位皮肤科医生评估了受试者的皮肤类型（烧伤或晒黑的倾向）和光化性皮肤损伤的程度。参与者每年接受一次皮肤检查，平均随访4年。在5232名可能符合条件的个体中，1805人参加了试验。我们排除了112例仅因皮肤癌接受过放射治疗的患者和3例缺少是否接受过放射治疗信息的患者，留下1690例患者进行分析。在每个研究年度中，大约4%的患者死亡或因其他原因停止参与。我们使用比例风险模型检查了随访期间与放射治疗史（非NMSC原因）相关的首次新组织病理学证实的BCC和SCC的发生时间。采用多终点生存模型比较BCC和SCC的发病率比（rr）。我们还使用纵向分析方法来计算每个研究年度与放射治疗相关的每个人的新发BCC和SCC肿瘤的RR。使用这种方法，我们还评估了治疗年龄、潜伏期和治疗类型的潜在改变作用。所有P值均采用双侧显著性统计检验。结果：在我们研究的参与者中，597例发生了新的BCC （n = 1553个肿瘤），118例发生了新的SCC （n = 179个肿瘤）。首次出现新BCC的时间与既往放射治疗相关(RR = 1.7； 95%可信区间（RR = 1.7； 95%可信区间[CI] = 1.4-2.0和RR = 1.0; 95% CI = 0.6-1.7； RRs之间的差异P = 0.03）。总BCC肿瘤的RR略高（RR = 2.3, 95% CI = 1.7 ~ 3.1），但对于SCC仍是一致的（RR = 1.0, 95% CI = 0.5 ~ 1.9）。BCC风险似乎随着接触年龄和初始治疗时间的增加而增加，尽管这些影响仅在统计学上具有边际意义(趋势P = .06和。07年,分别)。此外，与其他情况相比，BCC的风险与痤疮治疗的相关性更强（RR = 3.3; 95% CI = 2.1-5.2）。结论和意义：我们的数据表明，接受治疗性放疗与BCC相关，但与SCC无关。电离辐射暴露与皮肤癌风险之间关系的几个方面尚未完全了解，需要继续调查。
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 risk 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 individuals 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 exclused 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 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. Several aspects of the relationship of ionizing radiation exposure to the risk for skin cancer are not yet fully understood and warrant continued investigation.