Kony S J, de Vathaire F, Chompret A, Shamsaldim A, Grimaud E, Raquin M A, Oberlin O, Brugières L, Feunteun J, Eschwège F, Chavaudra J, Lemerle J, Bonaïti-Pellié C
Research Unit of Cancer Epidemiology (U351 INSERM), Villejuif, France.
Lancet. 1997 Jul 12;350(9071):91-5. doi: 10.1016/S0140-6736(97)01116-1.
Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment.
We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child.
Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially.
Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.
放疗和化疗与第二原发性恶性肿瘤（SMN）风险增加相关。SMN与家族聚集性之间的关联也已得到证实。本研究的目的是调查家族因素在SMN风险中的作用及其与治疗效果的潜在相互作用。
我们设计了一项病例对照研究，选取了25例患SMN的儿童（病例组）和96例癌症治疗后未患SMN的儿童（对照组），这些儿童来自1953年至1985年间在我们机构接受治疗的649名儿童队列。获取了患者和对照的完整家族史，并定义了家族指数以评估家族聚集程度。估算了每个儿童每次放疗疗程中身体151个部位的辐射剂量。
在25例SMN病例的家庭成员中，有10例患有早发性（≤45岁）癌症，而96例对照的亲属中有8例。与无早发性癌症家族史的患者相比，有一个或多个患病家庭成员的患者患SMN的优势比为4.7（95%可信区间1.3 - 17.1；p = 0.02）。调整局部辐射剂量并排除已知易患SMN的患者（p53突变携带者和患有神经纤维瘤病的患者）后，这一风险并未受到实质性影响。
遗传因素和接触电离辐射对SMN风险均有独立影响。当有早发性癌症家族史时，对接受癌症治疗的儿童进行随访应格外警惕。
