医学
体质指数
队列
遗传力
人口
全基因组关联研究
人口学
儿童白血病
队列研究
儿童癌症
肿瘤科
儿科
癌症
遗传学
内科学
单核苷酸多态性
白血病
基因型
生物
淋巴细胞白血病
社会学
基因
环境卫生
作者
Melissa A. Richard,Austin L. Brown,John W. Belmont,Michael E. Scheurer,Vidal M. Arroyo,Kayla Foster,Kathleen D. Kern,Melissa M. Hudson,Wendy Leisenring,M. Fatih Okcu,Yadav Sapkota,Yutaka Yasui,Lindsay M. Morton,Stephen J. Chanock,Leslie L. Robison,Gregory T. Armstrong,Smita Bhatia,Kevin C. Oeffinger,Philip J. Lupo,Kala Y. Kamdar
出处
期刊:Cancer
[Wiley]
日期:2020-10-13
卷期号:127 (2): 310-318
被引量:6
摘要
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.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.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; PMeta < 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.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.
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