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Genetic variation in the body mass index of adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort
Author(s) -
Richard Melissa A.,
Brown Austin L.,
Belmont John W.,
Scheurer Michael E.,
Arroyo Vidal M.,
Foster Kayla L.,
Kern Kathleen D.,
Hudson Melissa M.,
Leisenring Wendy M.,
Okcu M. Fatih,
Sapkota Yadav,
Yasui Yutaka,
Morton Lindsay M.,
Chanock Stephen J.,
Robison Leslie L.,
Armstrong Gregory T.,
Bhatia Smita,
Oeffinger Kevin C.,
Lupo Philip J.,
Kamdar Kala Y.
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33258
Subject(s) - medicine , body mass index , cohort , heritability , population , genome wide association study , demography , cohort study , oncology , pediatrics , genetics , single nucleotide polymorphism , genotype , biology , environmental health , sociology , gene
Background Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. Methods Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2‐stage genome‐wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi‐square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. Results In a meta‐analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL ( LINC00856 rs575792008 and EMR1 rs62123082; P Meta < 5E–8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci ( P < 7.0E–5) were further identified. At 2 CRT‐interacting loci, DNA methylation patterns may have differed by age. Conclusions Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.