University of Oulu

Kiiski, J.I., Tervasmäki, A., Pelttari, L.M. et al. Breast Cancer Res Treat (2017) 166: 217. https://doi.org/10.1007/s10549-017-4388-0

FANCM mutation c.5791C>T is a risk factor for triple-negative breast cancer in the Finnish population

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Author: Kiiski, Johanna I.1; Tervasmäki, Anna2,3; Pelttari, Liisa M.1;
Organizations: 1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital
2Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu
3Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre
4School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, and Cancer Center of Eastern Finland, University of Eastern Finland
5Imaging Center, Clinical Pathology, Kuopio University Hospital
6School of Medicine, Institute of Clinical Medicine, Oncology, Kuopio
7Cancer Center, Kuopio University Hospital
8Division of Oncology and Pathology Department of Clinical Sciences Lund, Lund University
9Forensic Medicine, and Cancer Center of Eastern Finland, University of Eastern Finland
10BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, and Fimlab Laboratories Tampere
11Department of Pathology, University of Helsinki and Helsinki University Hospital
12Department of Oncology, University of Helsinki and Helsinki University Hospital
13Department of Clinical Genetics, University of Helsinki and Helsinki University Hospital
14Department of Obstetrics and Gynecology, Helsinki University Central Hospital (HUS)
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2017120755461
Language: English
Published: Springer Nature, 2017
Publish Date: 2017-12-08
Description:

Abstract

Purpose: The FANCM c.5101C>T nonsense mutation was previously found to associate with breast cancer in the Finnish population, especially among triple-negative cases. Here, we studied the prevalence of three other FANCM variants: c.5791C>T, which has been reported to predispose to familial breast cancer, and the c.4025_4026delCT and c.5293dupA variants recently identified in Finnish cancer patients.

Methods: We genotyped the FANCM c.5791C>mutation in 4806 invasive breast cancer patients, including BRCA1/2 mutation negative familial cases and unselected cases, and in 2734 healthy population controls from four different geographical areas of Finland. The association of the mutation with breast cancer risk among patient subgroups was statistically evaluated. We further analyzed the combined risk associated with c.5101C>T and c.5791C>T mutations. We also genotyped 526 unselected ovarian cancer patients for the c.5791C>T mutation and 862 familial breast cancer patients for the c.4025_4026delCT and c.5293dupA variants.

Results: The frequency of the FANCM c.5791C>T mutation was higher among breast cancer cases than in controls (OR 1.94, 95% CI 0.87–4.32, P = 0.11), with a statistically significant association with triple-negative breast cancer (OR 5.14, 95% CI 1.65–16.0, P = 0.005). The combined analysis for c.5101C>T and c.5791C>T carriers confirmed a strong association with breast cancer (OR 1.86, 95% CI 1.32–2.49, P = 0.0002), especially among the triple-negative patients (OR 3.08, 95% CI 1.77–5.35, P = 0.00007). For the other variants, only one additional c.4025_4026delCT carrier and no c.5293dupA carriers were observed.

Conclusions: These results support the role of FANCM as a breast cancer susceptibility gene, particularly for triple-negative breast cancer.

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Volume: 166
Issue: 1
Pages: 217 - 226
DOI: 10.1007/s10549-017-4388-0
OADOI: https://oadoi.org/10.1007/s10549-017-4388-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: Helsinki breast cancer study has been supported by the Helsinki University Central Hospital Research Fund, the Academy of Finland (266528), the Sigrid Juselius Foundation, the Cancer Society of Finland, the Finnish Cultural Foundation for LMP, and the Biomedicum Helsinki Foundation for JK. Oulu breast cancer study has been supported by the Academy of Finland (250083) for KP, and by the Academy of Finland (122715 and Center of Excellence 284605), the Cancer Society of Finland, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation, and the special Governmental EVO funds for Oulu University Hospital-based research activities for RW. The Kuopio breast cancer study was supported by the special Government Funding of Kuopio University Hospital Grants, The Cancer Society of Finland, and the strategic fund of the University of Eastern Finland.
Academy of Finland Grant Number: 266528
250083
122715
284605
Detailed Information: 266528 (Academy of Finland Funding decision)
250083 (Academy of Finland Funding decision)
122715 (Academy of Finland Funding decision)
284605 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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