Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

被引：4

作者：

Evans, D. Gareth ^{[1
]}

Sithambaram, Siva ^{[2
]}

van Veen, Elke Maria ^{[3
]}

Burghel, George J. ^{[4
]}

Schlecht, Helene ^{[5
]}

Harkness, Elaine F. ^{[3
]}

Byers, Helen ^{[6
]}

Ellingford, Jamie M. ^{[7
]}

Gandhi, Ashu ^{[8
]}

Howell, Sacha J. ^{[2
,9
]}

Howell, Anthony ^{[10
]}

Forde, Claire ^{[11
]}

Lalloo, Fiona ^{[12
]}

Newman, William G. ^{[13
]}

Smith, Miriam Jane ^{[14
]}

Woodward, Emma Roisin ^{[15
]}

机构：

[1] Univ Manchester, Div Evolut & Genom Sci, Sch Hlth Sci, Manchester M13 9WL, Lancs, England

[2] Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England

[3] Univ Manchester, Div Evolut & Genom Sci, Manchester, Lancs, England

[4] MFT, Genom Diagnost Lab, Manchester, Lancs, England

[5] Cent Manchester Univ Hosp NHS Fdn Trust, North West Genom Lab Hub, Manchester, Lancs, England

[6] Univ Manchester, Genom Med, Sch Hlth Sci Manchester, Manchester, Lancs, England

[7] Univ Manchester, Inst Human Dev, Sch Hlth Sci Manchester, Manchester, Lancs, England

[8] Wythenshawe Hosp Manchester Univ Fdn Trust, Prevent Breast Canc Ctr, Manchester, Lancs, England

[9] Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England

[10] Manchester Fdn Trust, Prevent Breast Canc Ctr, Manchester, Lancs, England

[11] Cent Manchester Univ Hosp NHS Fdn Trust, Clin Genet Serv, Manchester, Lancs, England

[12] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Ctr Genom Med, Clin Genet Serv, Manchester, Lancs, England

[13] Univ Manchester, Genet, Sch Hlth Sci, Manchester, Lancs, England

[14] Univ Manchester, Genet Med, Sch Hlth Sci, Manchester, Lancs, England

[15] MFT, Manchester Ctr Genom Med, Manchester, Lancs, England

来源：

JOURNAL OF MEDICAL GENETICS | 2023年 / 60卷 / 08期

关键词：

Genetics; Medical; BRCA2; MUTATIONS; WOMEN; PREVALENCE; PATHOLOGY;

D O I：

10.1136/jmg-2022-108790

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

PurposeTo investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC). MethodsWe undertook BRCA1/2 analysis in 311 women with DCIS and 392 with G1BC and extended panel testing (non-BRCA1/2) in 176/311 with DCIS and 156/392 with G1BC. We investigated PV detection by age at diagnosis, Manchester Score (MS), DCIS grade and receptor status. Results30/311 (9.6%) with DCIS and 16/392 with G1BC (4.1%) had a BRCA1/2 PV (p=0.003), and 24/176-(13.6%) and 7/156-(4.5%), respectively, a non-BRCA1/2 PV (p=0.004). Increasing MS was associated with increased likelihood of BRCA1/2 PV in both DCIS and G1BC, although the 10% threshold was not predictive for G1GB. 13/32 (40.6%) DCIS and 0/17 with G1BC <40 years had a non-BRCA1/2 PV (p<0.001). 0/16 DCIS G1 had a PV. For G2 and G3 DCIS, PV rates were 10/98 (BRCA1/2) and 9/90 (non-BRCA1/2), and 8/47 (BRCA1/2) and 8/45 (non-BRCA1/2), respectively. 6/9 BRCA1 and 3/26 BRCA2-associated DCIS were oestrogen receptor negative-(p=0.003). G1BC population testing showed no increased PV rate (OR=1.16, 95% CI 0.28 to 4.80). ConclusionDCIS is more likely to be associated with both BRCA1/2 and non-BRCA1/2 PVs than G1BC. Extended panel testing ought to be offered in young-onset DCIS where PV detection rates are highest.

引用

页码：740 / 746

页数：7

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