Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers
Open accessAbstract
The purpose of this study was to quantify the risk of cancers other than melanoma among family members of CDKN2A mutation carriers using data from the Genes, Environment and Melanoma study. Relative risks (RRs) of all non-melanoma cancers among first-degree relatives (FDRs) of melanoma patients with CDKN2A mutations (n = 65) and FDRs of melanoma patients without mutations (n = 3537) were calculated as the ratio of estimated event rates (number of cancers/total person-years) in FDRs of carriers vs noncarriers with exact Clopper-Pearson-type tests and 95% confidence intervals (CIs). All statistical tests were two-sided. There were 56 (13.1%) non-melanoma cancers reported among 429 FDRs of mutation carriers and 2199 (9.4%) non-melanoma cancers in 23 452 FDRs of noncarriers. The FDRs of carriers had an increased risk of any cancer other than melanoma (56 cancers among 429 FDRs of carrier probands vs 2199 cancers among 23 452 FDRs of noncarrier probands; RR = 1.5, 95% CI = 1.2 to 2.0, P = .005), gastrointestinal cancer (20 cancers among 429 FDRs of carrier probands vs 506 cancers among 23 452 FDRs of noncarrier probands; RR = 2.4, 95% CI = 1.4 to 3.7, P = .001), and pancreatic cancer (five cancers among 429 FDRs of carrier probands vs 41 cancers among 23 452 FDRs of noncarrier probands; RR = 7.4, 95% CI = 2.3 to 18.7, P = .002). Wilms tumor was reported in two FDRs of carrier probands and three FDRs of noncarrier probands (RR = 40.4, 95% CI = 3.4 to 352.7, P = .005). The lifetime risk of any cancer other than melanoma among CDKN2A mutation carriers was estimated as 59.0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype.
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Germline mutations in specific genes are associated with developing pancreatic ductal adenocarcinoma.
“germline mutations in specific genes are associated with developing the condition.26–28”
From Early detection of pancreatic cancer (2020) · cites this paper as [28]
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- Authors
- Mukherjee, B., DeLancey, J. O., Raskin, L., Everett, J., Jeter, J., Begg, C. B., Orlow, I., Berwick, M., Armstrong, B. K., Kricker, A., Marrett, L. D., Millikan, R. C., Culver, H. A., Rosso, S., Zanetti, R., Kanetsky, P. A., From, L., & Gruber, S. B.
- Affiliations
- University of Michigan (US)
- University of Southern California (US)
- ORCID
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-25
- Volume
- 104
- Issue
- 12
- Pages
- 953-956
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC3379723
- OpenAlex
- W2113061788
- Cited by
- 42
- References
- 27
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (CA014089, CA046592)
- National Cancer Institute (CA014089, CA 156608, CA 83180, R03CA156608, CA 98-018, CA 046592, CA 131010, R01CA112243, R01CA131010, U01CA083180, R01CA098018, P30CA046592, P30CA014089)
- National Institute of Environmental Health Sciences (P30ES010126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- CDKN2A mutation, familial cancer risk, first-degree relatives, melanoma, gastrointestinal cancer, pancreatic cancer, Wilms tumor, lifetime cancer risk, hereditary cancer predisposition, genetic susceptibility, relative risk, cancer prevention recommendations, cancer treatment recommendations, cancer survivorship
- MeSH terms
- Adult, Aged, Aged, 80 and over, Family, Female, Genotype, Heterozygote, Humans, Male, Middle Aged, Mutation, Neoplasms, Risk Factors, United States, Age Distribution, Risk Assessment, Cyclin-Dependent Kinase Inhibitor p16, Genetic Predisposition to Disease
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