Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 166, Issue 1, Pages 217-226Publisher
SPRINGER
DOI: 10.1007/s10549-017-4388-0
Keywords
FANCM; Breast cancer; Triple-negative breast cancer; Familial breast cancer; DNA repair
Categories
Funding
- Helsinki University Central Hospital Research Fund
- Academy of Finland [266528, 250083, 122715]
- Sigrid Juselius Foundation
- Cancer Society of Finland
- Finnish Cultural Foundation
- Biomedicum Helsinki Foundation
- Academy of Finland (Center of Excellence) [284605]
- University of Oulu
- University of Oulu Support Foundation
- special Governmental EVO funds for Oulu University Hospital
- Kuopio University Hospital Grants
- University of Eastern Finland
- Cancer Foundation Finland sr [130168, 110135, 150147, 160104] Funding Source: researchfish
- Academy of Finland (AKA) [122715, 266528, 122715, 266528] Funding Source: Academy of Finland (AKA)
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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. 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. 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. These results support the role of FANCM as a breast cancer susceptibility gene, particularly for triple-negative breast cancer.
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