Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancerCitation formats

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Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancer. / Woodward, Emma; Van Veen, Elke; Forde, Claire; Harkness, Elaine; Byers, Helen; Ellingford, Jamie; Bowers, Naomi; Wallace, Andrew J ; Howell, Sacha; Howell, Tony; Lalloo, Fiona; Newman, William; Smith, Miriam J; Evans, D Gareth.

In: Genetics in Medicine, 13.05.2021.

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@article{dfcb5e129089441d84acdc86b0ff2f74,
title = "Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancer",
abstract = "Purpose: 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. Methods: Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial non-mucinous ovarian cancer and 1567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. Results: 35 PALB2 and 44 CHEK2_1100delC PGVs were detected in patients [odds ratio (OR) PALB2 breast-ovarian=5.90 (95% CIs:1.92-18.36), CHEK2 breast-ovarian=4.46 (95% CIs:1.86-10.46); PALB2 breast=6.16 (95% CIs:1.98-19.21), CHEK2 breast=4.89 (95% CIs:2.01-11.34). Grade3-ERpositive-HER2negative, grade3 and triple negative (TN) tumours were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service [respectively: 15/43, 254/1843, P=0.0005; 28/37, 562/1381, P=0.0001; 12/43, 204/1639, P<0.0001). PALB2_PGV likelihood increased with increasing Manchester Score (MS) [MS<15=17/1763, MS 20-39=11/520, P=0.04] but not for CHEK2_1100delC [MS<15=29/1762, MS 20-39=4/520]. PALB2 PGVs showed perfect segregation in 20/20 first degree relatives with breast cancer, compared with 7/13 for CHEK2_1100delC (P=0.002). Conclusion: PALB2 PGVs and CHEK2_1100delC together account for ~2.5% of familial breast/ovarian cancer risk. PALB2 PGVs are associated with grade3, TN and grade3-ERpositive-HER2negative breast tumours. ",
author = "Emma Woodward and {Van Veen}, Elke and Claire Forde and Elaine Harkness and Helen Byers and Jamie Ellingford and Naomi Bowers and Wallace, {Andrew J} and Sacha Howell and Tony Howell and Fiona Lalloo and William Newman and Smith, {Miriam J} and Evans, {D Gareth}",
year = "2021",
month = may,
day = "13",
language = "English",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams & Wilkins",

}

RIS

TY - JOUR

T1 - Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancer

AU - Woodward, Emma

AU - Van Veen, Elke

AU - Forde, Claire

AU - Harkness, Elaine

AU - Byers, Helen

AU - Ellingford, Jamie

AU - Bowers, Naomi

AU - Wallace, Andrew J

AU - Howell, Sacha

AU - Howell, Tony

AU - Lalloo, Fiona

AU - Newman, William

AU - Smith, Miriam J

AU - Evans, D Gareth

PY - 2021/5/13

Y1 - 2021/5/13

N2 - Purpose: 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. Methods: Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial non-mucinous ovarian cancer and 1567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. Results: 35 PALB2 and 44 CHEK2_1100delC PGVs were detected in patients [odds ratio (OR) PALB2 breast-ovarian=5.90 (95% CIs:1.92-18.36), CHEK2 breast-ovarian=4.46 (95% CIs:1.86-10.46); PALB2 breast=6.16 (95% CIs:1.98-19.21), CHEK2 breast=4.89 (95% CIs:2.01-11.34). Grade3-ERpositive-HER2negative, grade3 and triple negative (TN) tumours were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service [respectively: 15/43, 254/1843, P=0.0005; 28/37, 562/1381, P=0.0001; 12/43, 204/1639, P<0.0001). PALB2_PGV likelihood increased with increasing Manchester Score (MS) [MS<15=17/1763, MS 20-39=11/520, P=0.04] but not for CHEK2_1100delC [MS<15=29/1762, MS 20-39=4/520]. PALB2 PGVs showed perfect segregation in 20/20 first degree relatives with breast cancer, compared with 7/13 for CHEK2_1100delC (P=0.002). Conclusion: PALB2 PGVs and CHEK2_1100delC together account for ~2.5% of familial breast/ovarian cancer risk. PALB2 PGVs are associated with grade3, TN and grade3-ERpositive-HER2negative breast tumours.

AB - Purpose: 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. Methods: Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial non-mucinous ovarian cancer and 1567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. Results: 35 PALB2 and 44 CHEK2_1100delC PGVs were detected in patients [odds ratio (OR) PALB2 breast-ovarian=5.90 (95% CIs:1.92-18.36), CHEK2 breast-ovarian=4.46 (95% CIs:1.86-10.46); PALB2 breast=6.16 (95% CIs:1.98-19.21), CHEK2 breast=4.89 (95% CIs:2.01-11.34). Grade3-ERpositive-HER2negative, grade3 and triple negative (TN) tumours were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service [respectively: 15/43, 254/1843, P=0.0005; 28/37, 562/1381, P=0.0001; 12/43, 204/1639, P<0.0001). PALB2_PGV likelihood increased with increasing Manchester Score (MS) [MS<15=17/1763, MS 20-39=11/520, P=0.04] but not for CHEK2_1100delC [MS<15=29/1762, MS 20-39=4/520]. PALB2 PGVs showed perfect segregation in 20/20 first degree relatives with breast cancer, compared with 7/13 for CHEK2_1100delC (P=0.002). Conclusion: PALB2 PGVs and CHEK2_1100delC together account for ~2.5% of familial breast/ovarian cancer risk. PALB2 PGVs are associated with grade3, TN and grade3-ERpositive-HER2negative breast tumours.

M3 - Article

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

ER -