FANCM c.5101C > T mutation associates with breast cancer survival and treatment outcome

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Kiiski , J , Fagerholm , R , Tervasmaki , A , Pelttari , L M , Khan , S , Jamshidi , M , Mantere , T , Pylkas , K , Bartek , J , Bartkova , J , Mannermaa , A , Tengstrom , M , Kosma , V-M , Winqvist , R , Kallioniemi , A , Aittomäki , K , Blomqvist , C & Nevanlinna , H 2016 , ' FANCM c.5101C > T mutation associates with breast cancer survival and treatment outcome ' , International Journal of Cancer , vol. 139 , no. 12 , pp. 2760-2770 .

Title: FANCM c.5101C > T mutation associates with breast cancer survival and treatment outcome
Author: Kiiski, Johanna; Fagerholm, Rainer; Tervasmaki, Anna; Pelttari, Liisa M.; Khan, Sofia; Jamshidi, Maral; Mantere, Tuomo; Pylkas, Katri; Bartek, Jiri; Bartkova, Jirina; Mannermaa, Arto; Tengstrom, Maria; Kosma, Veli-Matti; Winqvist, Robert; Kallioniemi, Anne; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli
Contributor organization: Clinicum
Department of Obstetrics and Gynecology
Kristiina Aittomäki / Principal Investigator
Department of Medical and Clinical Genetics
Department of Oncology
HUS Gynecology and Obstetrics
Date: 2016-12
Language: eng
Number of pages: 11
Belongs to series: International Journal of Cancer
ISSN: 0020-7136
Abstract: Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C> T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple-negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C> T mutation carriers and 3,832 non-carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C>T mutation associated with poor 10-year breast cancer-specific survival (hazard ratio (HR) 51.66, 95% confidence interval (CI) 1.09-2.52, p=0.018), with a more pronounced survival effect among familial cases (HR=2.93, 95% CI 1.5-5.76, p=1.80 x 10 23). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR=1.8, 95% CI 1.09-2.98, p=0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR=3.43, 95% CI 1.6-7.34, p=1.50x10(-3)) but not among radiotherapy treated patients (HR=1.35, 95% CI 0.82-2.23, p=0.237). Significant interaction was found between the mutation and radiotherapy (p=0.040). Immunohistochemical analyses show that c.5101C> T carriers have reduced PAR-activity. Our results suggest that FANCM c.5101C>T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.
Subject: FANCM
breast cancer
DNA repair
3122 Cancers
3123 Gynaecology and paediatrics
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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