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HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.

ABSTRACT: Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant. Although the proband of the F3 with PTC was HABP2 wild type, three relatives presented the variant. Five of 170 healthy Brazilian individuals with no family history of BC or PTC and three of 50 sporadic PTC presented the p.G534E. These findings suggested no association of this variant with our familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes have pathogenic effects in the risk of familial PTC development.

SUBMITTER: Pinheiro M

PROVIDER: S-EPMC5522276 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.

Pinheiro Maisa M Drigo Sandra Aparecida SA Tonhosolo Renata R Andrade Sonia C S SCS Marchi Fabio Albuquerque FA Jurisica Igor I Kowalski Luiz Paulo LP Achatz Maria Isabel MI Rogatto Silvia Regina SR

Oncotarget 20170601 25

Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so ...[more]

PMID: 28402931

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Project description:ImportanceFamily history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood.ObjectivesTo investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements.Design, setting, and participantsThis single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020.ExposuresFamily history of breast cancer (FHBC).Main outcomes and measuresThe primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set.ResultsOf 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected.Conclusions and relevanceIn this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.

Dataset Information

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.

Publications

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.

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