Publication

Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants

Overbeek, K. A., Rodríguez-Girondo, M. D., Wagner, A., van der Stoep, N., van den Akker, P. C., Oosterwijk, J. C., van Os, T. A., van der Kolk, L. E., Vasen, H. F. A., Hes, F. J., Cahen, D. L., Bruno, M. J. & Potjer, T. P., 1-Jun-2020, In : JOURNAL OF MEDICAL GENETICS. 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Overbeek, K. A., Rodríguez-Girondo, M. D., Wagner, A., van der Stoep, N., van den Akker, P. C., Oosterwijk, J. C., ... Potjer, T. P. (2020). Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants. JOURNAL OF MEDICAL GENETICS. https://doi.org/10.1136/jmedgenet-2019-106562

Author

Overbeek, Kasper A ; Rodríguez-Girondo, Mar Dm ; Wagner, Anja ; van der Stoep, Nienke ; van den Akker, Peter C ; Oosterwijk, Jan C ; van Os, Theo A ; van der Kolk, Lizet E ; Vasen, Hans F A ; Hes, Frederik J ; Cahen, Djuna L ; Bruno, Marco J ; Potjer, Thomas P. / Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants. In: JOURNAL OF MEDICAL GENETICS. 2020.

Harvard

Overbeek, KA, Rodríguez-Girondo, MD, Wagner, A, van der Stoep, N, van den Akker, PC, Oosterwijk, JC, van Os, TA, van der Kolk, LE, Vasen, HFA, Hes, FJ, Cahen, DL, Bruno, MJ & Potjer, TP 2020, 'Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants', JOURNAL OF MEDICAL GENETICS. https://doi.org/10.1136/jmedgenet-2019-106562

Standard

Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants. / Overbeek, Kasper A; Rodríguez-Girondo, Mar Dm; Wagner, Anja; van der Stoep, Nienke; van den Akker, Peter C; Oosterwijk, Jan C; van Os, Theo A; van der Kolk, Lizet E; Vasen, Hans F A; Hes, Frederik J; Cahen, Djuna L; Bruno, Marco J; Potjer, Thomas P.

In: JOURNAL OF MEDICAL GENETICS, 01.06.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Overbeek KA, Rodríguez-Girondo MD, Wagner A, van der Stoep N, van den Akker PC, Oosterwijk JC et al. Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants. JOURNAL OF MEDICAL GENETICS. 2020 Jun 1. https://doi.org/10.1136/jmedgenet-2019-106562


BibTeX

@article{7a2a9aeea1ac4c88b28ab898f7b62444,
title = "Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants",
abstract = "BACKGROUND: Pathogenic variants in the CDKN2A gene are generally associated with the development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist and the extent of PDAC risk is not well established for many variants.METHODS: Using the Dutch national familial melanoma database, we identified all families with a pathogenic CDKN2A variant and investigated the occurrence of PDAC within these families. We also estimated the standardised incidence ratio and lifetime PDAC risk for carriers of a highly prevalent variant in these families.RESULTS: We identified 172 families in which 649 individuals carried 15 different pathogenic variants. The most prevalent variant was the founder mutation c.225_243del (p16-Leiden, 484 proven carriers). Second most prevalent was c.67G>C (55 proven carriers). PDAC developed in 95 of 163 families (58{\%}, including 373 of 629 proven carriers) harbouring a variant with an effect on the p16INK4a protein, whereas PDAC did not occur in the 9 families (20 proven carriers) with a variant affecting only p14ARF. In the c.67G>C families, PDAC occurred in 12 of the 251 (5{\%}) persons at risk. The standardised incidence ratio was 19.1 (95{\%} CI 8.3 to 33.6) and the cumulative PDAC incidence at age 75 years (lifetime risk) was 19{\%} (95{\%} CI 7.5{\%} to 30.1{\%}).CONCLUSIONS: Our results support the notion that pathogenic CDKN2A variants affecting the p16INK4a protein, including c.67G>C, are associated with increased PDAC risk and carriers of such variants should be offered pancreatic cancer surveillance. There is no clinical evidence that impairment of only the p14ARF protein leads to an increased PDAC risk.",
author = "Overbeek, {Kasper A} and Rodr{\'i}guez-Girondo, {Mar Dm} and Anja Wagner and {van der Stoep}, Nienke and {van den Akker}, {Peter C} and Oosterwijk, {Jan C} and {van Os}, {Theo A} and {van der Kolk}, {Lizet E} and Vasen, {Hans F A} and Hes, {Frederik J} and Cahen, {Djuna L} and Bruno, {Marco J} and Potjer, {Thomas P}",
note = "{\circledC} Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.",
year = "2020",
month = "6",
day = "1",
doi = "10.1136/jmedgenet-2019-106562",
language = "English",
journal = "JOURNAL OF MEDICAL GENETICS",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants

AU - Overbeek, Kasper A

AU - Rodríguez-Girondo, Mar Dm

AU - Wagner, Anja

AU - van der Stoep, Nienke

AU - van den Akker, Peter C

AU - Oosterwijk, Jan C

AU - van Os, Theo A

AU - van der Kolk, Lizet E

AU - Vasen, Hans F A

AU - Hes, Frederik J

AU - Cahen, Djuna L

AU - Bruno, Marco J

AU - Potjer, Thomas P

N1 - © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - BACKGROUND: Pathogenic variants in the CDKN2A gene are generally associated with the development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist and the extent of PDAC risk is not well established for many variants.METHODS: Using the Dutch national familial melanoma database, we identified all families with a pathogenic CDKN2A variant and investigated the occurrence of PDAC within these families. We also estimated the standardised incidence ratio and lifetime PDAC risk for carriers of a highly prevalent variant in these families.RESULTS: We identified 172 families in which 649 individuals carried 15 different pathogenic variants. The most prevalent variant was the founder mutation c.225_243del (p16-Leiden, 484 proven carriers). Second most prevalent was c.67G>C (55 proven carriers). PDAC developed in 95 of 163 families (58%, including 373 of 629 proven carriers) harbouring a variant with an effect on the p16INK4a protein, whereas PDAC did not occur in the 9 families (20 proven carriers) with a variant affecting only p14ARF. In the c.67G>C families, PDAC occurred in 12 of the 251 (5%) persons at risk. The standardised incidence ratio was 19.1 (95% CI 8.3 to 33.6) and the cumulative PDAC incidence at age 75 years (lifetime risk) was 19% (95% CI 7.5% to 30.1%).CONCLUSIONS: Our results support the notion that pathogenic CDKN2A variants affecting the p16INK4a protein, including c.67G>C, are associated with increased PDAC risk and carriers of such variants should be offered pancreatic cancer surveillance. There is no clinical evidence that impairment of only the p14ARF protein leads to an increased PDAC risk.

AB - BACKGROUND: Pathogenic variants in the CDKN2A gene are generally associated with the development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist and the extent of PDAC risk is not well established for many variants.METHODS: Using the Dutch national familial melanoma database, we identified all families with a pathogenic CDKN2A variant and investigated the occurrence of PDAC within these families. We also estimated the standardised incidence ratio and lifetime PDAC risk for carriers of a highly prevalent variant in these families.RESULTS: We identified 172 families in which 649 individuals carried 15 different pathogenic variants. The most prevalent variant was the founder mutation c.225_243del (p16-Leiden, 484 proven carriers). Second most prevalent was c.67G>C (55 proven carriers). PDAC developed in 95 of 163 families (58%, including 373 of 629 proven carriers) harbouring a variant with an effect on the p16INK4a protein, whereas PDAC did not occur in the 9 families (20 proven carriers) with a variant affecting only p14ARF. In the c.67G>C families, PDAC occurred in 12 of the 251 (5%) persons at risk. The standardised incidence ratio was 19.1 (95% CI 8.3 to 33.6) and the cumulative PDAC incidence at age 75 years (lifetime risk) was 19% (95% CI 7.5% to 30.1%).CONCLUSIONS: Our results support the notion that pathogenic CDKN2A variants affecting the p16INK4a protein, including c.67G>C, are associated with increased PDAC risk and carriers of such variants should be offered pancreatic cancer surveillance. There is no clinical evidence that impairment of only the p14ARF protein leads to an increased PDAC risk.

U2 - 10.1136/jmedgenet-2019-106562

DO - 10.1136/jmedgenet-2019-106562

M3 - Article

C2 - 32482799

JO - JOURNAL OF MEDICAL GENETICS

JF - JOURNAL OF MEDICAL GENETICS

SN - 0022-2593

ER -

ID: 127088594