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. 2012 Jun 20;104(12):953-6.
doi: 10.1093/jnci/djs221. Epub 2012 Apr 24.

Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers

Bhramar Mukherjee  1 , John Oliver Delancey, Leon Raskin, Jessica Everett, Joanne Jeter, Colin B Begg, Irene Orlow, Marianne Berwick, Bruce K Armstrong, Anne Kricker, Loraine D Marrett, Robert C Millikan, Hoda Anton Culver, Stefano Rosso, Roberto Zanetti, Peter A Kanetsky, Lynn From, Stephen B Gruber; GEM Study Investigators
Affiliations

Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers

Bhramar Mukherjee et al. J Natl Cancer Inst. .

Abstract

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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Figures

Figure 1
Figure 1
Age-specific cumulative risks for all non-melanoma cancers, all gastrointestinal (GI) cancers, and colorectal cancer in CDKN2A mutation carriers as obtained by a kin-cohort analysis. The dashed line represents the 95% bootstrap confidence interval.
See this image and copyright information in PMC

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