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Cancer. 2017 Oct 15;123(20):3925-3932. doi: 10.1002/cncr.30817. Epub 2017 Jun 28.

Germline genetic variants in men with prostate cancer and one or more additional cancers.

Author information

1
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
3
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
4
Cancer Genetics Clinic, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.

Abstract

BACKGROUND:

Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer.

METHODS:

Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome.

RESULTS:

Sequencing identified approximately 3500 variants. Nine protein-truncating deleterious mutations were found across 6 genes, including BRCA2, ataxia telangiectasia mutated (ATM), mutL homolog 1 (MLH1), BRCA1 interacting protein C-terminal helicase 1 (BRIP1), partner and localizer of BRCA2 (PALB2), and fibroblast growth factor receptor 3 (FGFR3). Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer-predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing.

CONCLUSIONS:

Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. Cancer 2017;123:3925-32. © 2017 American Cancer Society.

KEYWORDS:

gene panel; genetic testing; germline variants; multiple primary malignant neoplasms; prostate cancer

PMID:
28657667
PMCID:
PMC6108085
DOI:
10.1002/cncr.30817
[Indexed for MEDLINE]
Free PMC Article

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