Frequency of pathogenic germline variants in CDH1, BRCA2, CHEK2, PALB2, BRCA1 and TP53 in sporadic lobular breast cancer

TY - JOUR

T1 - Frequency of pathogenic germline variants in CDH1, BRCA2, CHEK2, PALB2, BRCA1 and TP53 in sporadic lobular breast cancer

AU - Petridis, Christos

AU - Arora, Iteeka

AU - Shah, Vandna

AU - Moss, Charlotte L.

AU - Mera, Anca

AU - Clifford, Angela

AU - Gillett, Cheryl

AU - Pinder, Sarah E

AU - Tomlinson, Ian

AU - Roylance, Rebecca

AU - Simpson, Michael A

AU - Sawyer, Elinor J

PY - 2019/7

Y1 - 2019/7

N2 - Background: Invasive lobular breast cancer (ILC) accounts for ~15% of invasive breast carcinomas and is commonly associated with lobular carcinoma in situ (LCIS). Both have been shown to have higher familial risks than the more common ductal cancers. However there is little data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in ILC. The aim of this study was to assess the frequency of germline variants in CDH1, BRCA2, BRCA1, CHEK2, PALB2 and TP53 in sporadic ILC and LCIS diagnosed in women aged 60 years or less. Methods: Access Array technology (Fluidigm) was used to amplify all exons of CDH1, BRCA2, BRCA1, TP53, CHEK2 and PALB2 using a custom made targeted sequencing panel in 1,434 cases of ILC and 368 cases of pure LCIS together with 1,611 controls. Results: Case-control analysis revealed an excess of pathogenic variants in BRCA2, CHEK2, PALB2 and CDH1 in women with ILC. CHEK2 was the only gene that showed an association with pure LCIS (OR = 9.90, 95% CI 3.42-28.66, P = 1.4 x10-5) with a larger effect size seen in LCIS compared to ILC (OR = 4.31, 95% CI 1.61-11.58, P = 1.7 x10-3). Conclusions: 11% of patients with ILC aged

AB - Background: Invasive lobular breast cancer (ILC) accounts for ~15% of invasive breast carcinomas and is commonly associated with lobular carcinoma in situ (LCIS). Both have been shown to have higher familial risks than the more common ductal cancers. However there is little data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in ILC. The aim of this study was to assess the frequency of germline variants in CDH1, BRCA2, BRCA1, CHEK2, PALB2 and TP53 in sporadic ILC and LCIS diagnosed in women aged 60 years or less. Methods: Access Array technology (Fluidigm) was used to amplify all exons of CDH1, BRCA2, BRCA1, TP53, CHEK2 and PALB2 using a custom made targeted sequencing panel in 1,434 cases of ILC and 368 cases of pure LCIS together with 1,611 controls. Results: Case-control analysis revealed an excess of pathogenic variants in BRCA2, CHEK2, PALB2 and CDH1 in women with ILC. CHEK2 was the only gene that showed an association with pure LCIS (OR = 9.90, 95% CI 3.42-28.66, P = 1.4 x10-5) with a larger effect size seen in LCIS compared to ILC (OR = 4.31, 95% CI 1.61-11.58, P = 1.7 x10-3). Conclusions: 11% of patients with ILC aged

UR - https://www.scopus.com/pages/publications/85068780358

U2 - 10.1158/1055-9965.EPI-18-1102

DO - 10.1158/1055-9965.EPI-18-1102

M3 - Article

SN - 1055-9965

VL - 28

SP - 1162

EP - 1168

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 7

ER -