Format

Send to

Choose Destination
J Natl Cancer Inst. 2019 Jun 19. pii: djz124. doi: 10.1093/jnci/djz124. [Epub ahead of print]

Germline pathogenic variants in 7,636 Japanese patients with prostate cancer and 12,366 controls.

Author information

1
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
2
Department of Genetic Medicine and Services, National Cancer Centre Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
3
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
4
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
5
Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
6
Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Centre Research Institute, 4-9-13 Yohnan, Tochigi 320-0834, Japan.
7
Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku,Tokyo 108-8639, Japan.
8
Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
9
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
10
Division of Genetics and Population Health, QIMR Berghofer Medical Research Institute, Brisbane, 300 Herston Rd, Herston, Queensland 4006, Australia.
11
RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.

Abstract

BACKGROUND:

Genetic testing has been conducted in patients with prostate cancer (PCa) using multi-gene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants.

METHODS:

We sequenced eight genes associated with hereditary PCa in 7,636 unselected Japanese patients with PCa and 12,366 male, cancer-free controls. We assigned clinical significance for all 1,456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and controls to calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided.

RESULTS:

We identified 136 pathogenic variants, and 2.9% of patients and 0.8% of controls had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P < 0.001, OR = 5.65, 95% CI = 3.55-9.32), HOXB13 (P < 0.001, OR = 4.73, 95% CI = 2.84-8.19), and ATM (P < 0.001, OR = 2.86, 95% CI = 1.63-5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis, more often had smoking and alcohol drinking histories, and family histories of breast, pancreatic, lung, and liver cancers.

CONCLUSION:

This largest sequencing study of PCa heredity provides additional evidence to the latest consensus among clinicians for developing genetic testing guidelines for PCa.

PMID:
31214711
DOI:
10.1093/jnci/djz124

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center