PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Melissa C. Southey; David E. Goldgar; Robert Winqvist; Katri Pylkäs; Fergus Couch; Marc Tischkowitz; William D. Foulkes; Joe Dennis; Kyriaki Michailidou; Elizabeth J. van Rensburg; Tuomas Heikkinen; Heli Nevanlinna; John L. Hopper; Thilo Dörk; Kathleen B.M. Claes; Jorge Reis-Filho; Zhi Ling Teo; Paolo Radice; Irene Catucci; Paolo Peterlongo; Helen Tsimiklis; Fabrice A. Odefrey; James G. Dowty; Marjanka K. Schmidt; Annegien Broeks; Frans B. Hogervorst; Senno Verhoef; Jane Carpenter; Christine Clarke; Rodney J. Scott; Peter A. Fasching; Lothar Haeberle; Arif B. Ekici; Matthias W. Beckmann; Julian Peto; Isabel dos-Santos-Silva; Olivia Fletcher; Nichola Johnson; Manjeet K. Bolla; Elinor J. Sawyer; Ian Tomlinson; Michael J. Kerin; Nicola Miller; Federik Marme; David J. Hunter; Nick Orr; Michael Jones; Ian Campbell; Hui Cai; John R. McLaughlin; kConFab Investigators66; Australian Ovarian Cancer Study Group65,66

doi:10.1136/jmedgenet-2016-103839

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Melissa C. Southey^*
, David E. Goldgar
, Robert Winqvist
, Katri Pylkäs
, Fergus Couch
, Marc Tischkowitz
, William D. Foulkes
, Joe Dennis
, Kyriaki Michailidou
, Elizabeth J. van Rensburg
, Tuomas Heikkinen
, Heli Nevanlinna
, John L. Hopper
, Thilo Dörk
, Kathleen B.M. Claes
, Jorge Reis-Filho
, Zhi Ling Teo
, Paolo Radice
, Irene Catucci
, Paolo Peterlongo

Helen Tsimiklis, Fabrice A. Odefrey, James G. Dowty, Marjanka K. Schmidt, Annegien Broeks, Frans B. Hogervorst, Senno Verhoef, Jane Carpenter, Christine Clarke, Rodney J. Scott, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Julian Peto, Isabel dos-Santos-Silva, Olivia Fletcher, Nichola Johnson, Manjeet K. Bolla, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Federik Marme, David J. Hunter, Nick Orr, Michael Jones, Ian Campbell, Hui Cai, John R. McLaughlin, kConFab Investigators66, Australian Ovarian Cancer Study Group65,66

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

195 Citations (Scopus)

283 Downloads (Pure)

Abstract

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T > G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10^-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10^-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Original language	English
Pages (from-to)	800-811
Number of pages	12
Journal	Journal of Medical Genetics
Volume	53
Issue number	12
Early online date	23 Nov 2016
DOIs	https://doi.org/10.1136/jmedgenet-2016-103839
Publication status	Published - 01 Dec 2016
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank the following for their contributions to this study: Qin Wang (BCAC), Lesley McGuffog, and Ken Offit (CIMBA), Andrew Lee, and Ed Dicks and the staff of the Centre for Genetic Epidemiology Laboratory, staff of the CNIO genotyping unit, Sylvie LaBoissière and Frederic Robidoux and the staff of the McGill University and Génome Québec Innovation Centre, staff of the Copenhagen DNA laboratory, and Sharon A Windebank, Christopher A Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. The authors also thank UM1 CA167552 (Willett) Cancer Epidemiology Cohort in Male Health Professionals, P01 CA87969 (Stampfer) Dietary and Hormonal Determinants of Cancer in Women, UM1 CA186107 (Stampfer) Long term multidisciplinary study of cancer in women: The Nurses' Health Study, R01CA141298 (Stampfer) Growth Factors and Lethal Prostate Cancer Signature, NCI: K07-CA80668 DAMD17-02-1-0669 NIH/National Center for Research Resources/General Clinical Research Center grant MO1-RR000056, R01CA095023, P50-CA159981, NCI CCSG award P30-CA008748 (Memorial Sloan Kettering Cancer Center), Department of Defense (W81XWH-07-0449), National Health and Medical Research Council of Australia APP1029974 and APP1061177, Deutsche Krebshilfe (Maier), Wellcome Trust Centre for Human Genetics from the Wellcome Trust (090532/Z/09/Z). The authors thank the National Institute of Health Research for their support to The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, CRUK C8197/A10123), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537-the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, the Ovarian Cancer Research Fund and Susan G Komen (WF). Further information about the financial report received is outlined in the supplementary file online.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
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Southey, M. C., Goldgar, D. E., Winqvist, R., Pylkäs, K., Couch, F., Tischkowitz, M., Foulkes, W. D., Dennis, J., Michailidou, K., van Rensburg, E. J., Heikkinen, T., Nevanlinna, H., Hopper, J. L., Dörk, T., Claes, K. B. M., Reis-Filho, J., Teo, Z. L., Radice, P., Catucci, I., ... Australian Ovarian Cancer Study Group65,66 (2016). PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. Journal of Medical Genetics, 53(12), 800-811. https://doi.org/10.1136/jmedgenet-2016-103839

@article{307ffae388844bc6a50442e5f1687c3a,

title = "PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS",

abstract = "Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T > G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95\% CI 1.39 to 8.52, p=7.1{\texttimes}10-5), PALB2 c.3113G > A OR 4.21 (95\% CI 1.84 to 9.60, p=6.9{\texttimes}10-8) and ATM c.7271T > G OR 11.0 (95\% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95\% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95\% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95\% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95\% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95\% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.",

author = "Southey, \{Melissa C.\} and Goldgar, \{David E.\} and Robert Winqvist and Katri Pylk{\"a}s and Fergus Couch and Marc Tischkowitz and Foulkes, \{William D.\} and Joe Dennis and Kyriaki Michailidou and \{van Rensburg\}, \{Elizabeth J.\} and Tuomas Heikkinen and Heli Nevanlinna and Hopper, \{John L.\} and Thilo D{\"o}rk and Claes, \{Kathleen B.M.\} and Jorge Reis-Filho and Teo, \{Zhi Ling\} and Paolo Radice and Irene Catucci and Paolo Peterlongo and Helen Tsimiklis and Odefrey, \{Fabrice A.\} and Dowty, \{James G.\} and Schmidt, \{Marjanka K.\} and Annegien Broeks and Hogervorst, \{Frans B.\} and Senno Verhoef and Jane Carpenter and Christine Clarke and Scott, \{Rodney J.\} and Fasching, \{Peter A.\} and Lothar Haeberle and Ekici, \{Arif B.\} and Beckmann, \{Matthias W.\} and Julian Peto and Isabel dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Bolla, \{Manjeet K.\} and Sawyer, \{Elinor J.\} and Ian Tomlinson and Kerin, \{Michael J.\} and Nicola Miller and Federik Marme and Hunter, \{David J.\} and Nick Orr and Michael Jones and Ian Campbell and Hui Cai and McLaughlin, \{John R.\} and \{kConFab Investigators66\} and \{Australian Ovarian Cancer Study Group65,66\}",

note = "Funding Information: The authors thank the following for their contributions to this study: Qin Wang (BCAC), Lesley McGuffog, and Ken Offit (CIMBA), Andrew Lee, and Ed Dicks and the staff of the Centre for Genetic Epidemiology Laboratory, staff of the CNIO genotyping unit, Sylvie LaBoissi{\`e}re and Frederic Robidoux and the staff of the McGill University and G{\'e}nome Qu{\'e}bec Innovation Centre, staff of the Copenhagen DNA laboratory, and Sharon A Windebank, Christopher A Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. The authors also thank UM1 CA167552 (Willett) Cancer Epidemiology Cohort in Male Health Professionals, P01 CA87969 (Stampfer) Dietary and Hormonal Determinants of Cancer in Women, UM1 CA186107 (Stampfer) Long term multidisciplinary study of cancer in women: The Nurses' Health Study, R01CA141298 (Stampfer) Growth Factors and Lethal Prostate Cancer Signature, NCI: K07-CA80668 DAMD17-02-1-0669 NIH/National Center for Research Resources/General Clinical Research Center grant MO1-RR000056, R01CA095023, P50-CA159981, NCI CCSG award P30-CA008748 (Memorial Sloan Kettering Cancer Center), Department of Defense (W81XWH-07-0449), National Health and Medical Research Council of Australia APP1029974 and APP1061177, Deutsche Krebshilfe (Maier), Wellcome Trust Centre for Human Genetics from the Wellcome Trust (090532/Z/09/Z). The authors thank the National Institute of Health Research for their support to The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, CRUK C8197/A10123), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537-the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, the Ovarian Cancer Research Fund and Susan G Komen (WF). Further information about the financial report received is outlined in the supplementary file online.",

year = "2016",

month = dec,

day = "1",

doi = "10.1136/jmedgenet-2016-103839",

language = "English",

volume = "53",

pages = "800--811",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "BMJ Publishing Group",

number = "12",

}

Southey, MC, Goldgar, DE, Winqvist, R, Pylkäs, K, Couch, F, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, JL, Dörk, T, Claes, KBM, Reis-Filho, J, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, FA, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Hunter, DJ, Orr, N, Jones, M, Campbell, I, Cai, H, McLaughlin, JR, kConFab Investigators66 & Australian Ovarian Cancer Study Group65,66 2016, 'PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS', Journal of Medical Genetics, vol. 53, no. 12, pp. 800-811. https://doi.org/10.1136/jmedgenet-2016-103839

TY - JOUR

T1 - PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

AU - Southey, Melissa C.

AU - Goldgar, David E.

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Couch, Fergus

AU - Tischkowitz, Marc

AU - Foulkes, William D.

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - van Rensburg, Elizabeth J.

AU - Heikkinen, Tuomas

AU - Nevanlinna, Heli

AU - Hopper, John L.

AU - Dörk, Thilo

AU - Claes, Kathleen B.M.

AU - Reis-Filho, Jorge

AU - Teo, Zhi Ling

AU - Radice, Paolo

AU - Catucci, Irene

AU - Peterlongo, Paolo

AU - Tsimiklis, Helen

AU - Odefrey, Fabrice A.

AU - Dowty, James G.

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Hogervorst, Frans B.

AU - Verhoef, Senno

AU - Carpenter, Jane

AU - Clarke, Christine

AU - Scott, Rodney J.

AU - Fasching, Peter A.

AU - Haeberle, Lothar

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Peto, Julian

AU - dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Bolla, Manjeet K.

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Marme, Federik

AU - Hunter, David J.

AU - Orr, Nick

AU - Jones, Michael

AU - Campbell, Ian

AU - Cai, Hui

AU - McLaughlin, John R.

AU - kConFab Investigators66

AU - Australian Ovarian Cancer Study Group65,66

N1 - Funding Information: The authors thank the following for their contributions to this study: Qin Wang (BCAC), Lesley McGuffog, and Ken Offit (CIMBA), Andrew Lee, and Ed Dicks and the staff of the Centre for Genetic Epidemiology Laboratory, staff of the CNIO genotyping unit, Sylvie LaBoissière and Frederic Robidoux and the staff of the McGill University and Génome Québec Innovation Centre, staff of the Copenhagen DNA laboratory, and Sharon A Windebank, Christopher A Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. The authors also thank UM1 CA167552 (Willett) Cancer Epidemiology Cohort in Male Health Professionals, P01 CA87969 (Stampfer) Dietary and Hormonal Determinants of Cancer in Women, UM1 CA186107 (Stampfer) Long term multidisciplinary study of cancer in women: The Nurses' Health Study, R01CA141298 (Stampfer) Growth Factors and Lethal Prostate Cancer Signature, NCI: K07-CA80668 DAMD17-02-1-0669 NIH/National Center for Research Resources/General Clinical Research Center grant MO1-RR000056, R01CA095023, P50-CA159981, NCI CCSG award P30-CA008748 (Memorial Sloan Kettering Cancer Center), Department of Defense (W81XWH-07-0449), National Health and Medical Research Council of Australia APP1029974 and APP1061177, Deutsche Krebshilfe (Maier), Wellcome Trust Centre for Human Genetics from the Wellcome Trust (090532/Z/09/Z). The authors thank the National Institute of Health Research for their support to The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, CRUK C8197/A10123), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537-the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, the Ovarian Cancer Research Fund and Susan G Komen (WF). Further information about the financial report received is outlined in the supplementary file online.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T > G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

AB - Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T > G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

U2 - 10.1136/jmedgenet-2016-103839

DO - 10.1136/jmedgenet-2016-103839

M3 - Article

AN - SCOPUS:84986246968

SN - 0022-2593

VL - 53

SP - 800

EP - 811

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 12

ER -

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

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Bibliographical note

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