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@ARTICLE{Hemminki:299011,
      author       = {K. Hemminki$^*$ and A. Försti$^*$ and O. Hemminki and R.
                      J. Scott and A. Hemminki},
      title        = {{A}ge-specific familial risks in cancer as clues to
                      germline genetic and environmental causes: focus on
                      colorectal, endometrial, prostate, kidney, breast and lung
                      cancers.},
      journal      = {Hereditary cancer in clinical practice},
      volume       = {23},
      number       = {1},
      issn         = {1731-2302},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-00421},
      pages        = {7},
      year         = {2025},
      note         = {#EA:Z999#},
      abstract     = {The Swedish Family-Cancer Database (FCD) is the largest
                      source of data on familial cancer in the world, including
                      practically complete family structures and individual cancer
                      diagnoses from the high-quality cancer registry. We present
                      a novel application of FCD by analyzing age-specific
                      familial risks and interpreting them through likely causes,
                      such as germline pathogenic variants and/or environmental
                      exposures.The basic assumption for this approach is that a
                      discrete familial clustering in a narrow age-interval is not
                      random but may provide causal clues. For this analysis we
                      selected reasonably common cancers to meaningfully
                      scrutinize familial risk through adulthood in which cancers
                      are diagnosed, that included colorectal (CRC) and
                      endometrial cancers, prostate and kidney cancers and breast
                      and lung cancers. The interpretation is based on the
                      literature. The highest familial relative risks for CRC and
                      endometrial cancers were found at ages 40-44 years, matching
                      the peak impact of mismatch repair gene mutations. However
                      endometrial cancer showed also a small early onset component
                      which could not be explained. Age-related familial risks for
                      breast, prostate and kidney cancers also matched data from
                      large-scale sequencing; these included the early onset
                      component in kidney cancer which was likely due to VHL
                      mutations. Age distribution of familial lung cancer was
                      unique in showing a wide peak extending from middle to old
                      ages, which would be consistent with a combination of direct
                      genetic effects and indirect influence on inheritance of
                      smoking dependence.The present review of age-specific
                      familial risks and age-of-onset data from the literature may
                      allow an interpretation that the familial and germline
                      landscapes are reasonably harmonious for relatively early
                      onset cancers but at higher ages no discrete peaks can be
                      found which may implicate attenuated impact of high-risk
                      genes and polygenic influence.},
      subtyp        = {Review Article},
      keywords     = {Age of onset (Other) / Early onset (Other) / Familial risk
                      (Other) / Germline genetics (Other) / Heredity (Other)},
      cin          = {Z999 / B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)Z999-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39985094},
      doi          = {10.1186/s13053-024-00301-8},
      url          = {https://inrepo02.dkfz.de/record/299011},
}