Abstract
To investigate the contribution of PALB2 pathogenic gene variants (PGVs, PALB2_PGV) and the CHEK2 c.1100delC (CHEK2_1100delC) PGV to familial breast and ovarian cancer, and PALB2_PGV associated breast cancer pathology. Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3,127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial nonmucinous ovarian cancer, and 1,567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. Thirty-five PALB2 and 44 CHEK2_1100delC PGVs were detected in patients (odds ratio [OR] PALB2 breast-ovarian = 5.90 [95% CI: 1.92-18.36], CHEK2 breast-ovarian = 4.46 [95% CI: 1.86-10.46], PALB2 breast = 6.16 [95% CI: 1.98-19.21], CHEK2 breast = 4.89 [95% CI: 2.01-11.34]). Grade 3 ER-positive HER2-negative, grade 3 and triple negative (TN) tumors were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service (respectively: 15/43, 254/1,843, P = 0.0005; 28/37, 562/1,381, P = 0.0001; 12/43, 204/1,639, P < 0.0001). PALB2_PGV likelihood increased with increasing Manchester score (MS) (MS < 15 = 17/1,763, MS 20-39 = 11/520, P = 0.04) but not for CHEK2_1100delC (MS < 15 = 29...Continue Reading
References
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·B NewmanM C King
Oct 25, 2000·British Journal of Cancer
Apr 23, 2002·Nature Genetics·Hanne Meijers-HeijboerUNKNOWN CHEK2-Breast Cancer Consortium
Mar 1, 2003·American Journal of Human Genetics·Mieke SchutteUNKNOWN Breast Cancer Linkage Consortium
Apr 4, 2003·Lancet·Fiona LallooUNKNOWN Early Onset Breast Cancer Study Group
Oct 7, 2004·Journal of Medical Genetics·G H de BockJ G M Klijn
Jan 4, 2007·Nature Genetics·Nazneen RahmanMichael R Stratton
Jun 23, 2009·Journal of Medical Genetics·D G R EvansA Howell
Aug 31, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nadine Tung, Daniel P Silver
Dec 7, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Nasim MavaddatUNKNOWN Consortium of Investigators of Modifiers of BRCA1/2
Dec 22, 2011·Familial Cancer·A MoranD G R Evans
Aug 8, 2014·The New England Journal of Medicine·Antonis C AntoniouMarc Tischkowitz
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
May 28, 2015·The New England Journal of Medicine·Douglas F EastonWilliam D Foulkes
Apr 18, 2018·Journal of Medical Genetics·Amy TaylorUNKNOWN UK Cancer Genetics Group (UK-CGG)
Oct 24, 2018·International Journal of Cancer. Journal International Du Cancer·J FerlayF Bray
Jan 15, 2019·Trends in Biochemical Sciences·Mandy DucyJean-Yves Masson
May 16, 2019·Journal of Human Genetics·Andromachi VagenaFlorentia Fostira
Dec 17, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xin YangMarc Tischkowitz
Jan 23, 2020·Cancer·Anne E WeidnerTuya Pal
Feb 25, 2020·Journal of the National Cancer Institute·Chunling HuFergus J Couch
Apr 18, 2020·Scientific Reports·Supriya BehlWilliam D Foulkes
Jul 29, 2020·Nature Medicine·J J GrzymskiJ T Lu
Oct 30, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nadine M TungJudy E Garber
Dec 16, 2020·Cancers·Anthony HowellD Gareth Evans
Dec 16, 2020·Nature Communications·Nina MarsSamuli Ripatti
Jan 21, 2021·The New England Journal of Medicine·Chunling HuFergus J Couch
Jan 21, 2021·The New England Journal of Medicine·UNKNOWN Breast Cancer Association ConsortiumDouglas F Easton