Whole-genome sequencing of childhood cancer survivors treated with cranial radiation therapy identifies 5p15.33 locus for stroke: A report from the St. Jude Lifetime Cohort study
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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其它資訊
摘要PURPOSE:
To identify genetic risk factors associated with risk of stroke among survivors of childhood cancer treated with cranial radiation therapy (CRT).

EXPERIMENTAL DESIGN:
We analyzed whole-genome sequencing (36.8-fold) data of 686 childhood cancer survivors of European ancestry [median (range): 40.4 (12.4-64.7) years old; 54% male] from the St. Jude Lifetime Cohort study treated with CRT, of whom 116 (17%) had clinically-diagnosed stroke. Association analyses (single-variant and Burden/SKAT tests) were performed, adjusting for demographic characteristics and childhood cancer treatment exposures.

RESULTS:
We identified a genome-wide significant association between 5p15.33 and stroke [rs112896372: hazard ratio (HR)=2.55; P=1.42 10-8], with a stronger association (HR=3.68) among survivors treated with CRT dose 25-50 Gray (Gy) and weaker associations among those treated with CRT doses <20 or 20-25 or >50 Gy (HRs=2.14, 2.40 and 2.28). The association was replicated in 90 CRT-exposed African survivors (HR=3.05;P=0.034). In CRT-exposed Europeans, rs112896372 significantly (P<0.001)improved predictive ability (AUC=0.717) for determining stroke risk than non-genetic factors alone (AUC=0.663) at 30 years since diagnosis, with significant improvement among African survivors (P=0.047).rs112896372 was further evaluated in three independent datasets including 1641 European (HR=1.54; P=0.055) and 316 African survivors (HR=1.88; P=0.283) not treated with CRT, and 166988 males in the UK Biobank (odds ratio=1.0012; P=0.042).

CONCLUSIONS:
A novel locus 5p15.33 is associated with stroke risk among childhood cancer survivors, with a possible CRT dose-specific effect. The locus is of potential clinical utility in characterizing individuals who may benefit from surveillance and intervention strategies.
出版社接受日期28.08.2019
著者Yadav Sapkota, Yin Ting Cheung, Wonjong Moon, Kyla Shelton, Carmen L. Wilson, Zhaoming Wang, Daniel A. Mulrooney, Jinghui Zhang, Gregory T. Armstrong, Melissa M. Hudson, Leslie L. Robison, Kevin R. Krull, Yutaka Yasui
期刊名稱Clinical Cancer Research
出版年份2019
月份11
卷號25
期次22
頁次6700 - 6708
國際標準期刊號1078-0432
電子國際標準期刊號1557-3265
語言美式英語

上次更新時間 2020-10-08 於 00:38