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@ARTICLE{Billaud:306176,
      author       = {A. Billaud and G. Figlioli and C. Mooser and I. Casamassima
                      and V. Azzoni and J. Srivatsa and M. Colombo and L. Caleca
                      and T. U. Ahearn and I. L. Andrulis and A. C. Antoniou and
                      M. W. Beckmann and S. Behrens$^*$ and M. Bermisheva and N.
                      V. Bogdanova and M. K. Bolla and B. Bonanni and T. Brüning
                      and N. J. Camp and A. Campbell and J. E. Castelao and M. H.
                      Cessna and J. Chang-Claude$^*$ and K. Czene and J. Dennis
                      and P. Devilee and T. Dörk and A. M. Dunning and M.
                      Eriksson and D. G. Evans and P. A. Fasching and J. D.
                      Figueroa and M. Gabrielson and M. Gago-Dominguez and A.
                      González-Neira and P. Guénel and A. Hadjisavvas and E.
                      Hahnen and U. Hamann$^*$ and P. Hillemanns and A.
                      Hollestelle and M. J. Hooning and R. Hoppe and A. Howell and
                      A. Jakubowska and V. N. Kristensen and J. Lubiński and M.
                      Lush and S. Manoukian and D. Mavroudis and R. L. Milne and
                      A. M. Mulligan and W. G. Newman and N. Obi and M. I.
                      Panayiotidis and G. Pita and M. U. Rashid$^*$ and V. Rhenius
                      and E. Saloustros and E. J. Sawyer and R. K. Schmutzler and
                      M. Shah and M. C. Southey and A. B. Spurdle and I. Tomlinson
                      and T. Truong and Q. Wang and C. Wendt and P. L. Auer and N.
                      J. Boddicker and C. Bodelon and E. S. Burnside and F. Chen
                      and F. J. Couch and S. M. Domchek and H. A. Eliassen and C.
                      Haiman and J. M. Hodge and C. Hu and H. Huang and S.
                      Lindstrom and M. E. Martinez and K. L. Nathanson and S. L.
                      Neuhausen and K. M. O'Brien and J. E. Olson and J. R. Palmer
                      and A. V. Patel and K. J. Ruddy and D. P. Sandler and L. R.
                      Teras and C. R. Weinberg and J. N. Weitzel and S. J. Winham
                      and S. Yadav and S. Yao and G. Zirpoli and M. Janatova and
                      Z. Kleibl and P. Kleiblova and J. Soukupova and Q. Zhao and
                      L. Devereux and P. A. James and I. G. Campbell and T.
                      Nguyen-Dumont and J. G. Dowty and N. Andrieu and F. Lesueur
                      and D. Stoppa-Lyonnet and M. d. l. Hoya and P. Radice and C.
                      S. Sørensen and P. Peterlongo},
      collaboration = {NBCS Collaborators and k. Investigators and C. consortium
                      and GENESIS},
      title        = {{L}arge-scale meta-analysis and precision functional assays
                      identify {FANCM} regions in which {PTV}s confer different
                      risks for {ER}-negative and triple-negative breast cancer.},
      journal      = {The breast},
      volume       = {85},
      issn         = {0960-9776},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-02416},
      pages        = {104619},
      year         = {2025},
      abstract     = {The breast cancer risk conferred by germline protein
                      truncating variants (PTVs) in known and putative breast
                      cancer genes has been extensively investigated. However, the
                      effect of FANCM PTVs on breast cancer risk remains unclear.
                      Our previous clinical, genetic and functional results on the
                      N-terminal p.Arg658∗ and the two C-terminal p.Gln1701∗
                      and p.Gly1906Alafs∗12 variants suggested that FANCM PTVs
                      may confer different risks for ER-negative (ER-neg) and
                      triple-negative (TN) breast cancer subtypes. Here, we
                      performed meta-analyses of seven studies totaling 144 681
                      breast cancer cases and 123 632 controls. FANCM PTVs were
                      tested for association with breast cancer risk overall and
                      the disease clinical subtypes by single variant and burden
                      analyses. Two CRISPR-Cas9-based functional assays were also
                      conducted to test the fitness of cells after knock-in of the
                      p.Arg658∗, p.Gln1701∗ and p.Gly1906Alafs∗12 PTVs and
                      the sensitivity of different FANCM regions to genome
                      editing. Our results suggest that the N-terminal FANCM
                      region upstream of p.Tyr725 harbors essential functions,
                      whereas downstream regions appear dispensable. This is
                      supported by our genetic data which indicate that all FANCM
                      PTVs, excluding the two C-terminal p.Gln1701∗ and
                      p.Gly1906Alafs∗12, are associated with an increased risk
                      of ER-neg (OR = 1.41, P = 0.023) and TN (OR = 1.64, P =
                      0.0023). Notably, PTVs upstream of AA position 670 are
                      associated with a moderate risk of developing TN breast
                      cancer, and that even when the p.Arg658∗ carriers were
                      excluded from the analysis. Importantly, our results confirm
                      previous data indicating that p.Arg658∗ carriers are at
                      moderate risk of developing ER-neg (OR = 2.08, P = 0.030)
                      and TN (OR = 3.26; P = 0.0034), whereas carriers of
                      p.Gln1701∗ and p.Gly1906Alafs∗12 should not be
                      considered at increased risk. Our data are useful for
                      counseling carriers of FANCM PTVs, but further analyses are
                      warranted to obtain more precise risk estimates.},
      keywords     = {Breast cancer risk (Other) / CRISPR-Cas9 (Other) / FANCM
                      (Other) / Gene editing (Other) / Genetic predisposition
                      (Other) / Meta-analysis (Other)},
      cin          = {C020 / B072},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331 / I:(DE-He78)B072-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41223770},
      doi          = {10.1016/j.breast.2025.104619},
      url          = {https://inrepo02.dkfz.de/record/306176},
}