母体健康、宫内和围产期暴露与后代甲状腺癌风险：一项基于北欧人群的巢式病例对照研究。
Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring: a Nordic population-based nested case-control study.
机构信息
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
出版信息
Lancet Diabetes Endocrinol. 2021 Feb;9(2):94-105. doi: 10.1016/S2213-8587(20)30399-5. Epub 2020 Dec 18.
BACKGROUND
Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified.
METHODS
In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs.
RESULTS
Of the 2437 cases, 1967 (81·4%) had papillary carcinomas, 1880 (77·1%) were women, and 1384 (56·7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1·14 [95% CI 1·05-1·23]) and congenital hypothyroidism (4·55 [1·58-13·08]); maternal diabetes before pregnancy (OR 1·69 [0·98-2·93]) and postpartum haemorrhage (OR 1·28 [1·06-1·55]); and (from registry data in Denmark) maternal hypothyroidism (18·12 [10·52-31·20]), hyperthyroidism (11·91 [6·77-20·94]), goiter (67·36 [39·89-113·76]), and benign thyroid neoplasms (22·50 [6·93-73·06]) were each associated with an increased risk of thyroid cancer in offspring.
INTERPRETATION
In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring.
FUNDING
Intramural Research Program of the National Cancer Institute (National Institutes of Health).
背景
与大多数其他恶性肿瘤（如乳腺癌[62 岁]或肺癌[71 岁]）相比，甲状腺癌的发病年龄往往更年轻（中位年龄 51 岁）。从青春期早期开始，女性甲状腺癌的发病率就高于男性。然而，与甲状腺癌风险增加相关的围产期和生命早期的风险因素很少被发现。
方法
在这项基于人群的巢式病例对照研究中，我们使用来自四个北欧国家的登记数据，评估了与母亲病史、妊娠并发症和出生特征相关的子女患甲状腺癌的风险。甲状腺癌患者（病例）为 1973 年至 2013 年在丹麦、1987 年至 2014 年在芬兰、1967 年至 2015 年在挪威或 1973 年至 2014 年在瑞典出生并随后诊断为原发性甲状腺癌的个体。每个病例均根据出生年份、性别、国家和出生县与至多 10 名无甲状腺癌的个体（对照）相匹配。在诊断甲状腺癌时，患有任何癌症（非黑色素瘤皮肤癌除外）的病例和匹配对照被排除在外。病例和匹配对照必须在诊断甲状腺癌时居住在出生国。采用条件逻辑回归模型计算比值比（OR）及其 95%置信区间（CI）。
结果
在 2437 例病例中，1967 例（81.4%）为乳头状癌，1880 例（77.1%）为女性，1384 例（56.7%）在 30 岁之前诊断（0-48 岁）。较高的出生体重（每公斤 1.14 的 OR [95%CI 1.05-1.23]）和先天性甲状腺功能减退症（4.55 [1.58-13.08]）；妊娠前母亲糖尿病（OR 1.69 [0.98-2.93]）和产后出血（OR 1.28 [1.06-1.55]）；以及（来自丹麦的登记数据）母亲甲状腺功能减退症（18.12 [10.52-31.20]）、甲状腺功能亢进症（11.91 [6.77-20.94]）、甲状腺肿（67.36 [39.89-113.76]）和良性甲状腺肿瘤（22.50 [6.93-73.06]）均与子女甲状腺癌风险增加相关。
解释
宫内暴露，特别是与母亲甲状腺疾病相关的暴露，可能对后代的甲状腺癌风险产生长期影响。
资金来源
美国国立癌症研究所（美国国立卫生研究院）内部研究计划。
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