Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer

详细信息    查看全文

• 作者：Sarah L. Kerns ; Richard G. Stock ; Nelson N. Stone ; Seth R. Blacksburg ; Lynda Rath ; Ana Vega ; Laura Fachal ; Antonio G¨®mez-Caama?o ; Dirk De Ruysscher ; Guido Lammering ; Matthew Parliament ; Michael Blackshaw ; Michael Sia ; Jamie Cesaretti ; Mitchell Terk ; Rosetta Hixson ; Barry S. Rosenstein ; Harry Ostrer
• 关键词：Radiogenomics ; Prostate cancer ; Rectal toxicity ; Genome-wide association study
• 刊名：Radiotherapy and Oncology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：107
• 期：3
• 页码：372-376
• 全文大小：248 K

文摘

Background and purpose

Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important.

Materials and methods

A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites.

Results

rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined m>pm>-values 5.4 ¡Á 10^?8 and 6.9 ¡Á 10^?7 respectively). Several other SNPs had m>pm>-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers¡¯ m>dm> = 5.0 ¡Á 10^?12 in the replication cohort).

Conclusions

This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.