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

Kiiski, Johanna I.; Tervasmäki, Anna; Pelttari, Liisa M; Khan, Sofia; Mantere, Tuomo; Pylkäs, Katri; Mannermaa, Arto; Tengström, Maria; Kvist, Anders LU and Borg, Åke LU , et al. (2017) In Breast Cancer Research and Treatment p.1-10
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... (More)

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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publication status
epub
subject
keywords
Breast cancer, DNA repair, Familial breast cancer, FANCM, Triple-negative breast cancer
in
Breast Cancer Research and Treatment
pages
10 pages
publisher
Springer
external identifiers
  • scopus:85023195004
ISSN
0167-6806
DOI
10.1007/s10549-017-4388-0
language
English
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yes
id
2bf1236e-9d4b-43a8-a82a-13c54694698d
date added to LUP
2017-08-02 15:59:19
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2017-08-03 09:55:00
@article{2bf1236e-9d4b-43a8-a82a-13c54694698d,
  abstract     = {<p>Purpose: The FANCM c.5101C&gt;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&gt;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&gt;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&gt;T and c.5791C&gt;T mutations. We also genotyped 526 unselected ovarian cancer patients for the c.5791C&gt;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&gt;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&gt;T and c.5791C&gt;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.</p>},
  author       = {Kiiski, Johanna I. and Tervasmäki, Anna and Pelttari, Liisa M and Khan, Sofia and Mantere, Tuomo and Pylkäs, Katri and Mannermaa, Arto and Tengström, Maria and Kvist, Anders and Borg, Åke and Kosma, Veli-Matti and Kallioniemi, Anne and Schleutker, Johanna and Bützow, Ralf and Blomqvist, Carl and Aittomäki, Kristiina and Winqvist, Robert and Nevanlinna, Heli},
  issn         = {0167-6806},
  keyword      = {Breast cancer,DNA repair,Familial breast cancer,FANCM,Triple-negative breast cancer},
  language     = {eng},
  month        = {07},
  pages        = {1--10},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {FANCM mutation c.5791C>T is a risk factor for triple-negative breast cancer in the Finnish population},
  url          = {http://dx.doi.org/10.1007/s10549-017-4388-0},
  year         = {2017},
}