Yang, Xin and Leslie, Goska and Doroszuk, Alicja and Schneider, Sandra and Allen, Jamie and Decker, Brennan and Dunning, Alison M. and Redman, James and Scarth, James and Plaskocinska, Inga and Luccarini, Craig and Shah, Mitul and Pooley, Karen and Dorling, Leila and Lee, Andrew and Adank, Muriel A. and Adlard, Julian and Aittomäki, Kristiina and Andrulis, Irene L. and Ang, Peter and Barwell, Julian and Bernstein, Jonine L. and Bobolis, Kristie and Borg, Åke and Blomqvist, Carl and Claes, Kathleen B.M. and Concannon, Patrick and Cuggia, Adeline and Culver, Julie O. and Damiola, Francesca and de Pauw, Antoine and Diez, Orland and Dolinsky, Jill S. and Domchek, Susan M. and Engel, Christoph and Evans, D. Gareth and Fostira, Florentia and Garber, Judy and Golmard, Lisa and Goode, Ellen L. and Gruber, Stephen B. and Hahnen, Eric and Hake, Christopher and Heikkinen, Tuomas and Hurley, Judith E. and Janavicius, Ramunas and Kleibl, Zdenek and Kleiblova, Petra and Konstantopoulou, Irene and Kvist, Anders and Laduca, Holly and Lee, Ann S.G. and Lesueur, Fabienne and Maher, Eamonn R. and Mannermaa, Arto and Manoukian, Siranoush and McFarland, Rachel and McKinnon, Wendy and Meindl, Alfons and Metcalfe, Kelly and Mohd Taib, Nur Aishah and Moilanen, Jukka and Nathanson, Katherine L. and Neuhausen, Susan and Ng, Pei Sze and Nguyen-Dumont, Tu and Nielsen, Sarah M. and Obermair, Florian and Offit, Kenneth and Olopade, Olufunmilayo I. and Ottini, Laura and Penkert, Judith and Pylkäs, Katri and Radice, Paolo and Ramus, Susan J. and Rudaitis, Vilius and Side, Lucy and Silva-Smith, Rachel and Silvestri, Valentina and Skytte, Anne-Bine and Slavin, Thomas and Soukupova, Jana and Tondini, Carlo and Trainer, Alison H. and Unzeitig, Gary and Usha, Lydia and van Overeem Hansen, Thomas and Whitworth, James and Wood, Marie and Yip, Cheng Har and Yoon, Sook-Yee and Yussuf, Amal and Zogopoulos, George and Goldgar, David and Hopper, John L. and Chenevix-Trench, Georgia and Pharoah, Paul and George, Sophia H.L. and Balmaña, Judith and Houdayer, Claude and James, Paul and El-Haffaf, Zaki and Ehrencrona, Hans and Janatova, Marketa and Peterlongo, Paolo and Nevanlinna, Heli and Schmutzler, Rita and Teo, Soo Hwang and Robson, Mark and Pal, Tuya and Couch, Fergus and Weitzel, Jeffrey N. and Elliott, Aaron and Southey, Melissa and Winqvist, Robert and Easton, Douglas F. and Foulkes, William D. and Antoniou, Antonis C. and Tischkowitz, Marc (2020) Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. Journal of Clinical Oncology, 38 (7). pp. 674-685. ISSN 0732-183X, DOI https://doi.org/10.1200/JCO.19.01907.
Full text not available from this repository.Abstract
PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers. © 2019 by American Society of Clinical Oncology.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Breast Neoplasms; Mutation; Panel testing |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 05 Jun 2020 02:31 |
| Last Modified: | 05 Jun 2020 02:31 |
| URI: | http://eprints.um.edu.my/id/eprint/24672 |
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