The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor

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The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor. / Brandão, Andreia; Paulo, Paula; Maia, Sofia; Pinheiro, Manuela; Peixoto, Ana; Cardoso, Marta; Silva, Maria P.; Santos, Catarina; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Muir, Kenneth; Schleutker, Johanna; Wang, Ying; Pashayan, Nora; Batra, Jyotsna; Grönberg, Henrik; Neal, David E.; Nordestgaard, Børge G.; Tangen, Catherine M.; Southey, Melissa C.; Wolk, Alicja; Albanes, Demetrius; Haiman, Christopher A.; Travis, Ruth C.; Stanford, Janet L.; Mucci, Lorelei A.; West, Catharine M.L.; Nielsen, Sune F.; Kibel, Adam S.; Cussenot, Olivier; Berndt, Sonja I.; Koutros, Stella; Sørensen, Karina Dalsgaard; Cybulski, Cezary; Grindedal, Eli Marie; Park, Jong Y.; Ingles, Sue A.; Maier, Christiane; Hamilton, Robert J.; Rosenstein, Barry S.; Vega, Ana; Kogevinas, Manolis; Wiklund, Fredrik; Penney, Kathryn L.; Brenner, Hermann; John, Esther M.; Kaneva, Radka; Logothetis, Christopher J.; Neuhausen, Susan L.; De Ruyck, Kim; UKGPCS Collaborators; The Profile Study Steering Committee; The Practical Consortium.

In: Cancers, Vol. 12, No. 11, 3254, 2020, p. 1-17.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Brandão, A, Paulo, P, Maia, S, Pinheiro, M, Peixoto, A, Cardoso, M, Silva, MP, Santos, C, Eeles, RA, Kote-Jarai, Z, Muir, K, Schleutker, J, Wang, Y, Pashayan, N, Batra, J, Grönberg, H, Neal, DE, Nordestgaard, BG, Tangen, CM, Southey, MC, Wolk, A, Albanes, D, Haiman, CA, Travis, RC, Stanford, JL, Mucci, LA, West, CML, Nielsen, SF, Kibel, AS, Cussenot, O, Berndt, SI, Koutros, S, Sørensen, KD, Cybulski, C, Grindedal, EM, Park, JY, Ingles, SA, Maier, C, Hamilton, RJ, Rosenstein, BS, Vega, A, Kogevinas, M, Wiklund, F, Penney, KL, Brenner, H, John, EM, Kaneva, R, Logothetis, CJ, Neuhausen, SL, De Ruyck, K, UKGPCS Collaborators, The Profile Study Steering Committee & The Practical Consortium 2020, 'The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor', Cancers, vol. 12, no. 11, 3254, pp. 1-17. https://doi.org/10.3390/cancers12113254

APA

Brandão, A., Paulo, P., Maia, S., Pinheiro, M., Peixoto, A., Cardoso, M., Silva, M. P., Santos, C., Eeles, R. A., Kote-Jarai, Z., Muir, K., Schleutker, J., Wang, Y., Pashayan, N., Batra, J., Grönberg, H., Neal, D. E., Nordestgaard, B. G., Tangen, C. M., ... The Practical Consortium (2020). The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor. Cancers, 12(11), 1-17. [3254]. https://doi.org/10.3390/cancers12113254

Vancouver

Brandão A, Paulo P, Maia S, Pinheiro M, Peixoto A, Cardoso M et al. The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor. Cancers. 2020;12(11):1-17. 3254. https://doi.org/10.3390/cancers12113254

Author

Brandão, Andreia ; Paulo, Paula ; Maia, Sofia ; Pinheiro, Manuela ; Peixoto, Ana ; Cardoso, Marta ; Silva, Maria P. ; Santos, Catarina ; Eeles, Rosalind A. ; Kote-Jarai, Zsofia ; Muir, Kenneth ; Schleutker, Johanna ; Wang, Ying ; Pashayan, Nora ; Batra, Jyotsna ; Grönberg, Henrik ; Neal, David E. ; Nordestgaard, Børge G. ; Tangen, Catherine M. ; Southey, Melissa C. ; Wolk, Alicja ; Albanes, Demetrius ; Haiman, Christopher A. ; Travis, Ruth C. ; Stanford, Janet L. ; Mucci, Lorelei A. ; West, Catharine M.L. ; Nielsen, Sune F. ; Kibel, Adam S. ; Cussenot, Olivier ; Berndt, Sonja I. ; Koutros, Stella ; Sørensen, Karina Dalsgaard ; Cybulski, Cezary ; Grindedal, Eli Marie ; Park, Jong Y. ; Ingles, Sue A. ; Maier, Christiane ; Hamilton, Robert J. ; Rosenstein, Barry S. ; Vega, Ana ; Kogevinas, Manolis ; Wiklund, Fredrik ; Penney, Kathryn L. ; Brenner, Hermann ; John, Esther M. ; Kaneva, Radka ; Logothetis, Christopher J. ; Neuhausen, Susan L. ; De Ruyck, Kim ; UKGPCS Collaborators ; The Profile Study Steering Committee ; The Practical Consortium. / The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor. In: Cancers. 2020 ; Vol. 12, No. 11. pp. 1-17.

Bibtex

@article{1ab96a5beea0417492541d662e321007,
title = "The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor",
abstract = "The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.",
keywords = "Cancer predisposition, CHEK2, Founder variant, Prostate cancer",
author = "Andreia Brand{\~a}o and Paula Paulo and Sofia Maia and Manuela Pinheiro and Ana Peixoto and Marta Cardoso and Silva, {Maria P.} and Catarina Santos and Eeles, {Rosalind A.} and Zsofia Kote-Jarai and Kenneth Muir and Johanna Schleutker and Ying Wang and Nora Pashayan and Jyotsna Batra and Henrik Gr{\"o}nberg and Neal, {David E.} and Nordestgaard, {B{\o}rge G.} and Tangen, {Catherine M.} and Southey, {Melissa C.} and Alicja Wolk and Demetrius Albanes and Haiman, {Christopher A.} and Travis, {Ruth C.} and Stanford, {Janet L.} and Mucci, {Lorelei A.} and West, {Catharine M.L.} and Nielsen, {Sune F.} and Kibel, {Adam S.} and Olivier Cussenot and Berndt, {Sonja I.} and Stella Koutros and S{\o}rensen, {Karina Dalsgaard} and Cezary Cybulski and Grindedal, {Eli Marie} and Park, {Jong Y.} and Ingles, {Sue A.} and Christiane Maier and Hamilton, {Robert J.} and Rosenstein, {Barry S.} and Ana Vega and Manolis Kogevinas and Fredrik Wiklund and Penney, {Kathryn L.} and Hermann Brenner and John, {Esther M.} and Radka Kaneva and Logothetis, {Christopher J.} and Neuhausen, {Susan L.} and {De Ruyck}, Kim and {UKGPCS Collaborators} and {The Profile Study Steering Committee} and {The Practical Consortium}",
year = "2020",
doi = "10.3390/cancers12113254",
language = "English",
volume = "12",
pages = "1--17",
journal = "Cancers",
issn = "2072-6694",
publisher = "M D P I AG",
number = "11",

}

RIS

TY - JOUR

T1 - The CHEK2 variant C.349A>G is associated with prostate cancer risk and carriers share a common ancestor

AU - Brandão, Andreia

AU - Paulo, Paula

AU - Maia, Sofia

AU - Pinheiro, Manuela

AU - Peixoto, Ana

AU - Cardoso, Marta

AU - Silva, Maria P.

AU - Santos, Catarina

AU - Eeles, Rosalind A.

AU - Kote-Jarai, Zsofia

AU - Muir, Kenneth

AU - Schleutker, Johanna

AU - Wang, Ying

AU - Pashayan, Nora

AU - Batra, Jyotsna

AU - Grönberg, Henrik

AU - Neal, David E.

AU - Nordestgaard, Børge G.

AU - Tangen, Catherine M.

AU - Southey, Melissa C.

AU - Wolk, Alicja

AU - Albanes, Demetrius

AU - Haiman, Christopher A.

AU - Travis, Ruth C.

AU - Stanford, Janet L.

AU - Mucci, Lorelei A.

AU - West, Catharine M.L.

AU - Nielsen, Sune F.

AU - Kibel, Adam S.

AU - Cussenot, Olivier

AU - Berndt, Sonja I.

AU - Koutros, Stella

AU - Sørensen, Karina Dalsgaard

AU - Cybulski, Cezary

AU - Grindedal, Eli Marie

AU - Park, Jong Y.

AU - Ingles, Sue A.

AU - Maier, Christiane

AU - Hamilton, Robert J.

AU - Rosenstein, Barry S.

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Wiklund, Fredrik

AU - Penney, Kathryn L.

AU - Brenner, Hermann

AU - John, Esther M.

AU - Kaneva, Radka

AU - Logothetis, Christopher J.

AU - Neuhausen, Susan L.

AU - De Ruyck, Kim

AU - UKGPCS Collaborators

AU - The Profile Study Steering Committee

AU - The Practical Consortium

PY - 2020

Y1 - 2020

N2 - The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

AB - The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

KW - Cancer predisposition

KW - CHEK2

KW - Founder variant

KW - Prostate cancer

U2 - 10.3390/cancers12113254

DO - 10.3390/cancers12113254

M3 - Journal article

C2 - 33158149

AN - SCOPUS:85096384312

VL - 12

SP - 1

EP - 17

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 11

M1 - 3254

ER -

ID: 252294762