Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample

Colin B. Begg, Irene Orlow, Amanda J. Hummer, Bruce K. Armstrong, Anne Kricker, Loraine D. Marrett, Robert C. Millikan, Stephen B. Gruber, Hoda Anton-Culver, Roberto Zanetti, Richard P. Gallagher, Terence Dwyer, Timothy R. Rebbeck, Nandita Mitra, Klaus Busam, Lynn From, Marianne Berwick, Melisa Litchfield, Paul Tucker, Nicola StephensTeresa Switzer, Elizabeth Theis, Noori Chowdhury, Louise Vanasse, Mark Purdue, David Northrup, Stefano Rosso, Carlotta Sacerdote, Nancy Leighton, Maureen Gildea, Joe Bonner, Joanne M Jeter, Judith Klotz, Homer Wilcox, Helen Weiss, Diane Mattingly, Jon Player, Chiu Kit Tse, Peter Kanetsky, Amy Walker, Saarene Panossian, Harvey Mohrenweiser, Richard Setlow

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalJournal of the National Cancer Institute
Volume97
Issue number20
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Melanoma
Mutation
Population
p16 Genes
Penetrance
Germ-Line Mutation
DNA
Italy
Canada
Cluster Analysis
Exons
Polymerase Chain Reaction
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Begg, C. B., Orlow, I., Hummer, A. J., Armstrong, B. K., Kricker, A., Marrett, L. D., ... Setlow, R. (2005). Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. Journal of the National Cancer Institute, 97(20), 1507-1515. https://doi.org/10.1093/jnci/dji312

Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. / Begg, Colin B.; Orlow, Irene; Hummer, Amanda J.; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D.; Millikan, Robert C.; Gruber, Stephen B.; Anton-Culver, Hoda; Zanetti, Roberto; Gallagher, Richard P.; Dwyer, Terence; Rebbeck, Timothy R.; Mitra, Nandita; Busam, Klaus; From, Lynn; Berwick, Marianne; Litchfield, Melisa; Tucker, Paul; Stephens, Nicola; Switzer, Teresa; Theis, Elizabeth; Chowdhury, Noori; Vanasse, Louise; Purdue, Mark; Northrup, David; Rosso, Stefano; Sacerdote, Carlotta; Leighton, Nancy; Gildea, Maureen; Bonner, Joe; Jeter, Joanne M; Klotz, Judith; Wilcox, Homer; Weiss, Helen; Mattingly, Diane; Player, Jon; Tse, Chiu Kit; Kanetsky, Peter; Walker, Amy; Panossian, Saarene; Mohrenweiser, Harvey; Setlow, Richard.

In: Journal of the National Cancer Institute, Vol. 97, No. 20, 10.2005, p. 1507-1515.

Research output: Contribution to journalArticle

Begg, CB, Orlow, I, Hummer, AJ, Armstrong, BK, Kricker, A, Marrett, LD, Millikan, RC, Gruber, SB, Anton-Culver, H, Zanetti, R, Gallagher, RP, Dwyer, T, Rebbeck, TR, Mitra, N, Busam, K, From, L, Berwick, M, Litchfield, M, Tucker, P, Stephens, N, Switzer, T, Theis, E, Chowdhury, N, Vanasse, L, Purdue, M, Northrup, D, Rosso, S, Sacerdote, C, Leighton, N, Gildea, M, Bonner, J, Jeter, JM, Klotz, J, Wilcox, H, Weiss, H, Mattingly, D, Player, J, Tse, CK, Kanetsky, P, Walker, A, Panossian, S, Mohrenweiser, H & Setlow, R 2005, 'Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample', Journal of the National Cancer Institute, vol. 97, no. 20, pp. 1507-1515. https://doi.org/10.1093/jnci/dji312
Begg, Colin B. ; Orlow, Irene ; Hummer, Amanda J. ; Armstrong, Bruce K. ; Kricker, Anne ; Marrett, Loraine D. ; Millikan, Robert C. ; Gruber, Stephen B. ; Anton-Culver, Hoda ; Zanetti, Roberto ; Gallagher, Richard P. ; Dwyer, Terence ; Rebbeck, Timothy R. ; Mitra, Nandita ; Busam, Klaus ; From, Lynn ; Berwick, Marianne ; Litchfield, Melisa ; Tucker, Paul ; Stephens, Nicola ; Switzer, Teresa ; Theis, Elizabeth ; Chowdhury, Noori ; Vanasse, Louise ; Purdue, Mark ; Northrup, David ; Rosso, Stefano ; Sacerdote, Carlotta ; Leighton, Nancy ; Gildea, Maureen ; Bonner, Joe ; Jeter, Joanne M ; Klotz, Judith ; Wilcox, Homer ; Weiss, Helen ; Mattingly, Diane ; Player, Jon ; Tse, Chiu Kit ; Kanetsky, Peter ; Walker, Amy ; Panossian, Saarene ; Mohrenweiser, Harvey ; Setlow, Richard. / Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. In: Journal of the National Cancer Institute. 2005 ; Vol. 97, No. 20. pp. 1507-1515.
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title = "Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample",
abstract = "Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58{\%} in Europe to 91{\%} in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53{\%} participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14{\%} (95{\%} CI = 8{\%} to 22{\%}) by age 50 years, 24{\%} (95{\%} CI = 15{\%} to 34{\%}) by age 70 years, and 28{\%} (95{\%} CI = 18{\%} to 40{\%}) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.",
author = "Begg, {Colin B.} and Irene Orlow and Hummer, {Amanda J.} and Armstrong, {Bruce K.} and Anne Kricker and Marrett, {Loraine D.} and Millikan, {Robert C.} and Gruber, {Stephen B.} and Hoda Anton-Culver and Roberto Zanetti and Gallagher, {Richard P.} and Terence Dwyer and Rebbeck, {Timothy R.} and Nandita Mitra and Klaus Busam and Lynn From and Marianne Berwick and Melisa Litchfield and Paul Tucker and Nicola Stephens and Teresa Switzer and Elizabeth Theis and Noori Chowdhury and Louise Vanasse and Mark Purdue and David Northrup and Stefano Rosso and Carlotta Sacerdote and Nancy Leighton and Maureen Gildea and Joe Bonner and Jeter, {Joanne M} and Judith Klotz and Homer Wilcox and Helen Weiss and Diane Mattingly and Jon Player and Tse, {Chiu Kit} and Peter Kanetsky and Amy Walker and Saarene Panossian and Harvey Mohrenweiser and Richard Setlow",
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TY - JOUR

T1 - Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample

AU - Begg, Colin B.

AU - Orlow, Irene

AU - Hummer, Amanda J.

AU - Armstrong, Bruce K.

AU - Kricker, Anne

AU - Marrett, Loraine D.

AU - Millikan, Robert C.

AU - Gruber, Stephen B.

AU - Anton-Culver, Hoda

AU - Zanetti, Roberto

AU - Gallagher, Richard P.

AU - Dwyer, Terence

AU - Rebbeck, Timothy R.

AU - Mitra, Nandita

AU - Busam, Klaus

AU - From, Lynn

AU - Berwick, Marianne

AU - Litchfield, Melisa

AU - Tucker, Paul

AU - Stephens, Nicola

AU - Switzer, Teresa

AU - Theis, Elizabeth

AU - Chowdhury, Noori

AU - Vanasse, Louise

AU - Purdue, Mark

AU - Northrup, David

AU - Rosso, Stefano

AU - Sacerdote, Carlotta

AU - Leighton, Nancy

AU - Gildea, Maureen

AU - Bonner, Joe

AU - Jeter, Joanne M

AU - Klotz, Judith

AU - Wilcox, Homer

AU - Weiss, Helen

AU - Mattingly, Diane

AU - Player, Jon

AU - Tse, Chiu Kit

AU - Kanetsky, Peter

AU - Walker, Amy

AU - Panossian, Saarene

AU - Mohrenweiser, Harvey

AU - Setlow, Richard

PY - 2005/10

Y1 - 2005/10

N2 - Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.

AB - Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.

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DO - 10.1093/jnci/dji312

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