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Published in: Breast Cancer Research and Treatment 1/2017

Open Access 01-11-2017 | Epidemiology

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

Authors: Johanna I. Kiiski, Anna Tervasmäki, Liisa M. Pelttari, Sofia Khan, Tuomo Mantere, Katri Pylkäs, Arto Mannermaa, Maria Tengström, Anders Kvist, Åke Borg, Veli-Matti Kosma, Anne Kallioniemi, Johanna Schleutker, Ralf Bützow, Carl Blomqvist, Kristiina Aittomäki, Robert Winqvist, Heli Nevanlinna

Published in: Breast Cancer Research and Treatment | Issue 1/2017

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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>T 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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Metadata
Title
FANCM mutation c.5791C>T is a risk factor for triple-negative breast cancer in the Finnish population
Authors
Johanna I. Kiiski
Anna Tervasmäki
Liisa M. Pelttari
Sofia Khan
Tuomo Mantere
Katri Pylkäs
Arto Mannermaa
Maria Tengström
Anders Kvist
Åke Borg
Veli-Matti Kosma
Anne Kallioniemi
Johanna Schleutker
Ralf Bützow
Carl Blomqvist
Kristiina Aittomäki
Robert Winqvist
Heli Nevanlinna
Publication date
01-11-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4388-0

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