University of Oulu

Susanna Koivuluoma, Anna Tervasmäki, Saila Kauppila, Robert Winqvist, Timo Kumpula, Outi Kuismin, Jukka Moilanen, Katri Pylkäs, Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer, European Journal of Cancer, Volume 143, 2021, Pages 46-51, ISSN 0959-8049,

Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer

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Author: Koivuluoma, Susanna1; Tervasmäki, Anna1; Kauppila, Saila2;
Organizations: 1Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, NordLab Oulu, University of Oulu, Oulu, Finland
2Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Clinical Genetics, Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-04-16


Background: Breast cancer is strongly influenced by hereditary risk factors. Yet, the known susceptibility genes and genomic loci explain only about half of the familial component of the disease. To identify novel breast cancer predisposing gene defects, here we have performed massive parallel sequencing for Northern Finnish breast cancer cases.

Methods: Ninety-eight breast cancer cases with indication of hereditary disease susceptibility were exome sequenced. Data filtering strategy focused on predictably deleterious rare variants that were still enriched in the sequenced cohort. Findings were confirmed with additional, geographically matched breast cancer cohorts.

Results: A recurrent heterozygous splice acceptor variant, c.918-1G>C, in SERPINA3, was identified, and it was significantly enriched both in the hereditary (6/201, 3.0%, p = 0.006, OR 5.1, 95% CI 1.7–14.8) and unselected breast cancer cohort (26/1569, 1.7%, p = 0.009, OR 2.8, 95% CI 1.3–6.2). SERPINA3 c.918-1G>C carriers were also significantly more likely to have a rare tumor subtype, medullary breast cancer, than the non-carriers (4/26, 15.4%, p = 0.000014, OR 42.9, 95% CI 11.7–157.1).

Conclusion: These findings demonstrate that c.918-1G>C germline variant in SERPINA3 gene, encoding a member of the serine protease inhibitor class, is a novel breast cancer predisposing allele.

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Series: European journal of cancer
ISSN: 0959-8049
ISSN-E: 1879-0852
ISSN-L: 0959-8049
Volume: 143
Pages: 46 - 51
DOI: 10.1016/j.ejca.2020.10.033
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by the Academy of Finland (grant numbers 307808, 314183, 335242) and the Cancer Foundation of Finland sr. Funders had no role in the study design, collection, analysis and interpretation of data, writing of the report and the decision to submit the article for publication.
Academy of Finland Grant Number: 307808
Detailed Information: 307808 (Academy of Finland Funding decision)
314183 (Academy of Finland Funding decision)
335242 (Academy of Finland Funding decision)
Copyright information: © 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (