Lehrer Steven, Green Sheryl, Rosenzweig Kenneth E
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA E-mail :
Asian Pac J Cancer Prev. 2016;17(6):2979-82.
High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence.
Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau.
We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (<0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (β = - 0.463, p = 0.002) but unrelated to age (β = - 0.080, p = 0.570) or obesity (β = - 0.180, p = 0.208).
The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.
高剂量电离辐射可诱发卵巢癌,但低剂量辐射对卵巢癌发生发展的影响尚未得到广泛研究。我们评估了低剂量辐射、总背景辐射以及在直肠乙状结肠癌和乳腺癌治疗过程中传递至卵巢的辐射对卵巢癌发病率的影响。
背景辐射测量数据来自《2011年美国辐射暴露变化评估》。卵巢癌发病率数据来自疾病控制与预防中心。乳腺癌和直肠乙状结肠癌后卵巢癌的标准化发病率(SIR)来自监测、流行病学和最终结果(SEER)数据。美国各州的肥胖数据来自疾病控制与预防中心。美国各州人口的平均年龄来自美国人口普查局。
我们根据监测、流行病学和最终结果(SEER)数据计算了标准化发病率(SIR),结果显示,在194,042例接受束流辐射治疗的乳腺癌病例中,治疗120个月及以上时有796例卵巢癌(0.41%);在283,875例未接受辐射治疗的乳腺癌病例中,治疗120个月及以上时有1,531例卵巢癌(0.54%)。两组卵巢癌发病率的差异具有显著性(<0.001,双侧Fisher精确检验)。从束流辐射至乳腺的少量散射至卵巢的辐射(约3.09厘戈瑞)似乎使卵巢癌风险降低了24%。在SEER数据中,13,099例接受束流辐射治疗的直肠或直肠乙状结肠交界处癌病例中,治疗120个月及以上时有20例卵巢癌(0.15%)。在33,305例未接受辐射治疗的直肠或直肠乙状结肠交界处癌病例中,治疗120个月及以上时有91例卵巢癌(0.27%)。两组卵巢癌发病率的差异具有显著性(p = 0.017,双侧Fisher精确检验)。换句话说,辐射至直肠和直肠乙状结肠且也到达卵巢的辐射使卵巢癌风险降低了44%。此外,白人女性卵巢癌与氡背景辐射(r = -0.465,p = 0.002)和总背景辐射(r = -0.456,p = 0.002)之间存在显著的负相关关系。由于年龄增加和肥胖是卵巢癌的危险因素,因此进行了多变量线性回归分析。卵巢癌发病率与氡背景之间的负相关关系具有显著性(β = -0.463,p = 0.002),但与年龄(β = -0.080,p = 0.570)或肥胖(β = -0.180,p = 0.208)无关。
低剂量辐射后卵巢癌风险的降低可能是辐射兴奋效应的结果。兴奋效应是对低毒素暴露的一种有利生物学反应。表现出兴奋效应的污染物或毒素在小剂量时与大剂量时具有相反的作用。就辐射而言,大剂量具有致癌性。然而,在美国辐射影响较高的州总体癌症发病率较低。此外,在美国进行过核武器试验的高辐射背景州肺癌发病率有所降低。卵巢癌风险增加的女性有两种选择。她们可以密切随访(监测)或立即进行预防性双侧输卵管卵巢切除术。然而,监测的效果值得怀疑。双侧输卵管卵巢切除术被认为更可取,尽管它存在手术并发症的风险。上述数据分析表明,低剂量盆腔照射可能是降低卵巢癌风险的一个不错的第三种选择。值得进行进一步研究以确定最低的最佳辐射剂量。