Cancer Risk in Individuals with Intellectual Disability in Sweden: A Population-Based Cohort Study

Qianwei Liu, Hans-Olov Adami, Abraham Reichenberg, Alexander Kolevzon, Fang Fang, Sven Sandin

A knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.

Intellectual disability (ID) is a lifelong impairment of cognition and adaptive behavior that emerges in childhood [1], affects around 1% of the world population [2], and is associated with increased morbidity and mortality [3–5]. For instance, individuals with ID generally have an abnormal level of intelligence quotient (IQ) (under 70) and deficiency in at least 2 adaptive behaviors in environment and social milieu [6]. The underlying causes of ID are heterogenous, including chromosomal abnormality, gene mutation, environmental factors, and prenatal factors [7]. The exact cause, however, is not identifiable for most individuals with ID [8].

Study Population

We used nationwide data from Sweden made available via the European Union’s Horizon 2020 research and innovation program RECAP preterm (Research on European Children and Adults Born Preterm; The study population consisted of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. The mothers of these individuals were identified through the Swedish Medical Birth Register, which covers 99% of all births in Sweden since 1973 [31]. Fathers were identified using the Swedish Multi-Generation Register [32].

The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID (15,334 with mild ID, 2,683 with moderate ID, 1,078 with severe ID, 450 with profound ID, and 8,411 with unspecified or other ID) and their 29,641 ID-free full siblings (Tables 1 and S4). Among individuals with ID, 9,878 had syndromic ID (35.3%), whereas 18,078 had idiopathic ID (64.7%). Compared with the reference group, individuals with ID were in general more likely to be male, with lower parental educational level, lower birth weight, lower Apgar score at 1 minute, and a higher prevalence of multiple birth, preterm birth, parental psychiatric history, and maternal smoking during pregnancy (Tables 1 and S4). Characteristics of ID by severity are described in S5 Table.

In the largest population-based cohort study to date, to our knowledge, we observed a 1.6-fold increased risk of any cancer among individuals with ID, compared with individuals without ID, up to age 43 years. There was also an increased risk for several cancer types, including cancer of the esophagus, stomach, small intestine, colon, pancreas, uterus, kidney, CNS, and other or unspecified sites, as well as AML and ALL. The risk of any cancer was higher for syndromic ID and for childhood cancer, but did not vary by sex, ID severity, birth weight, Apgar score at 1 minute, gestational age at birth, parental education, maternal smoking during pregnancy, or calendar year of birth. The sibling comparison showed no support for familial confounding of the observed association.

Citation: Liu Q, Adami H-O, Reichenberg A, Kolevzon A, Fang F, Sandin S (2021) Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study. PLoS Med 18(10): e1003840.

Editor: Wei Zheng, Vanderbilt University School of Medicine, UNITED STATES

Received: April 24, 2021; Accepted: October 8, 2021; Published: October 21, 2021

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data cannot be shared publicly owing to restrictions by law. Data can be requested through the Statistics Sweden ( and the Swedish National Board of Health and Welfare ( after approval by the Ethics Committees.

Funding: The study was supported by grants from the European Union (H2020-SC1: PM04-2016, grant for SS). This study was also supported by the Swedish Cancer Society (No. 20 0846 PjF, grant for FF), the Swedish Research Council for Health, Working Life and Welfare (No. 2017-00531, grant for FF), the China Scholarship Council (No. 201700260291, grant for QL) and the Karolinska Institute (Senior Researcher Award and Strategic Research Area in Epidemiology, grant for FF). The funding source had no role in study design, data collection, data analysis, data interpretation, writing of the scientific article, or the decision to submit the paper for publication.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AK reported research support from AMO pharma and consult to ovid, acadia, alkermes, jaguar, and ritrova. Other authors declared no competing interests.

Abbreviations: ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; CI, confidence interval; CNS, central nervous system; HR, hazard ratio; ID, intellectual disability; IQ, intelligence quotient; IR, incidence rate

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