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Cancer Epidemiol Biomarkers Prev. 2018 Nov;27(11):1364-1370. doi: 10.1158/1055-9965.EPI-17-1065. Epub 2018 Jul 23.

CDKN2A Germline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations.

Author information

1
Department of Oncology, Mayo Clinic, Rochester, Minnesota. Mcwilliams.robert@mayo.edu.
2
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
3
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
4
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
5
Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida.
6
Division of Epidemiology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
7
Departments of Medicine and Human Genetics, University of Chicago Medical Center, Chicago, Illinois.
8
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Department of Medicine, Division of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida.
10
Department of Medicine, Columbia University Medical Center, New York, New York.
11
Departments of Cancer Epidemiology and Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida.
12
Department of Epidemiology, Columbia University Medical Center, New York, New York.
13
Herbert Irving Comprehensive Cancer Center, New York, New York.
14
Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota.
15
Division of Oncology, Washington University, St. Louis, Missouri.

Abstract

Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects.Methods: We sequenced CDKN2A in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced.Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258_278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5-7.1; P = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0% (OR, 13.4; 95% CI, 4.9-36.7; P < 0.001) compared with NHW cases (0.4%).Conclusions: CDKN2A RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs.Impact: RCVs in CDKN2A are frequent in AAs and are associated with risk for pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 27(11); 1364-70. ©2018 AACR.

PMID:
30038052
PMCID:
PMC6214745
[Available on 2019-11-01]
DOI:
10.1158/1055-9965.EPI-17-1065

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