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

Bhramar Mukherjee, John Oliver Delancey, Leon Raskin, Jessica Everett, Joanne M 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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 23452 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 23452 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 23452 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 23452 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.

Original languageEnglish (US)
Pages (from-to)953-956
Number of pages4
JournalJournal of the National Cancer Institute
Volume104
Issue number12
DOIs
StatePublished - Jun 20 2012

Fingerprint

Mutation
Neoplasms
Melanoma
Confidence Intervals
Genotype
Gastrointestinal Neoplasms
Wilms Tumor
Pancreatic Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mukherjee, B., Delancey, J. O., Raskin, L., Everett, J., Jeter, J. M., Begg, C. B., ... Gruber, S. B. (2012). Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers. Journal of the National Cancer Institute, 104(12), 953-956. https://doi.org/10.1093/jnci/djs221

Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers. / Mukherjee, Bhramar; Delancey, John Oliver; Raskin, Leon; Everett, Jessica; Jeter, Joanne M; Begg, Colin B.; Orlow, Irene; Berwick, Marianne; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D.; Millikan, Robert C.; Culver, Hoda Anton; Rosso, Stefano; Zanetti, Roberto; Kanetsky, Peter A.; From, Lynn; Gruber, Stephen B.

In: Journal of the National Cancer Institute, Vol. 104, No. 12, 20.06.2012, p. 953-956.

Research output: Contribution to journalArticle

Mukherjee, B, Delancey, JO, Raskin, L, Everett, J, Jeter, JM, Begg, CB, Orlow, I, Berwick, M, Armstrong, BK, Kricker, A, Marrett, LD, Millikan, RC, Culver, HA, Rosso, S, Zanetti, R, Kanetsky, PA, From, L & Gruber, SB 2012, 'Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers', Journal of the National Cancer Institute, vol. 104, no. 12, pp. 953-956. https://doi.org/10.1093/jnci/djs221
Mukherjee, Bhramar ; Delancey, John Oliver ; Raskin, Leon ; Everett, Jessica ; Jeter, Joanne M ; Begg, Colin B. ; Orlow, Irene ; Berwick, Marianne ; Armstrong, Bruce K. ; Kricker, Anne ; Marrett, Loraine D. ; Millikan, Robert C. ; Culver, Hoda Anton ; Rosso, Stefano ; Zanetti, Roberto ; Kanetsky, Peter A. ; From, Lynn ; Gruber, Stephen B. / Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers. In: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 12. pp. 953-956.
@article{276fccd4b496439986088a84d99b09fa,
title = "Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers",
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 23452 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 23452 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 23452 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 23452 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.",
author = "Bhramar Mukherjee and Delancey, {John Oliver} and Leon Raskin and Jessica Everett and Jeter, {Joanne M} and Begg, {Colin B.} and Irene Orlow and Marianne Berwick and Armstrong, {Bruce K.} and Anne Kricker and Marrett, {Loraine D.} and Millikan, {Robert C.} and Culver, {Hoda Anton} and Stefano Rosso and Roberto Zanetti and Kanetsky, {Peter A.} and Lynn From and Gruber, {Stephen B.}",
year = "2012",
month = "6",
day = "20",
doi = "10.1093/jnci/djs221",
language = "English (US)",
volume = "104",
pages = "953--956",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers

AU - Mukherjee, Bhramar

AU - Delancey, John Oliver

AU - Raskin, Leon

AU - Everett, Jessica

AU - Jeter, Joanne M

AU - Begg, Colin B.

AU - Orlow, Irene

AU - Berwick, Marianne

AU - Armstrong, Bruce K.

AU - Kricker, Anne

AU - Marrett, Loraine D.

AU - Millikan, Robert C.

AU - Culver, Hoda Anton

AU - Rosso, Stefano

AU - Zanetti, Roberto

AU - Kanetsky, Peter A.

AU - From, Lynn

AU - Gruber, Stephen B.

PY - 2012/6/20

Y1 - 2012/6/20

N2 - 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 23452 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 23452 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 23452 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 23452 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.

AB - 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 23452 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 23452 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 23452 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 23452 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.

UR - http://www.scopus.com/inward/record.url?scp=84864143250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864143250&partnerID=8YFLogxK

U2 - 10.1093/jnci/djs221

DO - 10.1093/jnci/djs221

M3 - Article

C2 - 22534780

AN - SCOPUS:84864143250

VL - 104

SP - 953

EP - 956

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 12

ER -