METHODS: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models.
RESULTS: In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (Ptrend = 0.008).
CONCLUSIONS: Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors.
方法:我们使用了四个北欧国家的全国性卫生登记处,并进行了嵌套病例对照研究。我们纳入了40538例癌症病例(0-46岁)和481945例人口对照(按出生年份和国家匹配),出生于1967年至2014年。用比值比(OR)和95%置信区间(CI)计算兄弟姐妹有出生缺陷的个体的相对癌症风险。使用逻辑回归模型。
结果:在总研究人群(0-46岁)中,我们观察到兄弟姐妹有出生缺陷的个体和兄弟姐妹未受影响的个体之间的癌症风险没有总体差异(OR1.02;95%CI0.97-1.08);然而,淋巴和造血系统恶性肿瘤的风险升高(1.16;1.05-1.28).儿童癌症(0-19岁)的总体风险增加的个体的兄弟姐妹有出生缺陷(1.09;1.00-1.19),主要由淋巴瘤(1.35;1.09-1.66)驱动,神经母细胞瘤(1.51;1.11-2.05)和肾癌(5.03;1.73-14.6)。癌症的风险也随着有出生缺陷的兄弟姐妹的数量而增加(Ptrend=0.008)。
结论:兄弟姐妹有出生缺陷的个体(0-46岁)患癌症的总体风险没有升高,但儿童癌症(0-19岁)的风险增加。我们的新发现与出生缺陷和癌症的常见病因一致,例如共同的遗传易感性和环境因素。