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@ARTICLE{TenBroeke:148599,
      author       = {S. W. Ten Broeke and H. M. van der Klift and C. M. J. Tops
                      and S. Aretz and I. Bernstein and D. D. Buchanan and A. de
                      la Chapelle and G. Capella and M. Clendenning and C. Engel
                      and S. Gallinger and E. Gomez Garcia and J. C. Figueiredo
                      and R. Haile and H. L. Hampel and J. L. Hopper and N.
                      Hoogerbrugge and M. von Knebel Doeberitz$^*$ and L. Le
                      Marchand and T. G. W. Letteboer and M. A. Jenkins and A.
                      Lindblom and N. M. Lindor and A. R. Mensenkamp and P.
                      Møller and P. A. Newcomb and T. A. M. van Os and R.
                      Pearlman and M. Pineda and N. Rahner and E. J. W. Redeker
                      and M. J. W. Olderode-Berends and C. Rosty and H. K.
                      Schackert and R. Scott and L. Senter and L. Spruijt and V.
                      Steinke-Lange and M. Suerink and S. Thibodeau and Y. J. Vos
                      and A. Wagner and I. Winship and F. J. Hes and H. F. A.
                      Vasen and J. T. Wijnen and M. Nielsen and A. K. Win},
      title        = {{C}ancer {R}isks for {PMS}2-{A}ssociated {L}ynch
                      {S}yndrome.},
      journal      = {Journal of clinical oncology},
      volume       = {36},
      number       = {29},
      issn         = {1527-7755},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2019-03147},
      pages        = {2961 - 2968},
      year         = {2018},
      abstract     = {Lynch syndrome due to pathogenic variants in the DNA
                      mismatch repair genes MLH1, MSH2, and MSH6 is predominantly
                      associated with colorectal and endometrial cancer, although
                      extracolonic cancers have been described within the Lynch
                      tumor spectrum. However, the age-specific cumulative risk
                      (penetrance) of these cancers is still poorly defined for
                      PMS2-associated Lynch syndrome. Using a large data set from
                      a worldwide collaboration, our aim was to determine accurate
                      penetrance measures of cancers for carriers of heterozygous
                      pathogenic PMS2 variants.A modified segregation analysis was
                      conducted that incorporated both genotyped and nongenotyped
                      relatives, with conditioning for ascertainment to estimates
                      corrected for bias. Hazard ratios (HRs) and corresponding
                      $95\%$ CIs were estimated for each cancer site for mutation
                      carriers compared with the general population, followed by
                      estimation of penetrance.In total, 284 families consisting
                      of 4,878 first- and second-degree family members were
                      included in the analysis. PMS2 mutation carriers were at
                      increased risk for colorectal cancer (cumulative risk to age
                      80 years of $13\%$ $[95\%$ CI, $7.9\%$ to $22\%]$ for males
                      and $12\%$ $[95\%$ CI, $6.7\%$ to $21\%]$ for females) and
                      endometrial cancer $(13\%$ $[95\%$ CI, $7.0\%-24\%]),$
                      compared with the general population $(6.6\%,$ $4.7\%,$ and
                      $2.4\%,$ respectively). There was no clear evidence of an
                      increased risk of ovarian, gastric, hepatobiliary, bladder,
                      renal, brain, breast, prostate, or small bowel
                      cancer.Heterozygous PMS2 mutation carriers were at small
                      increased risk for colorectal and endometrial cancer but not
                      for any other Lynch syndrome-associated cancer. This finding
                      justifies that PMS2-specific screening protocols could be
                      restricted to colonoscopies. The role of risk-reducing
                      hysterectomy and bilateral salpingo-oophorectomy for PMS2
                      mutation carriers needs further discussion.},
      keywords     = {PMS2 protein, human (NLM Chemicals) / Mismatch Repair
                      Endonuclease PMS2 (NLM Chemicals)},
      cin          = {G105},
      ddc          = {610},
      cid          = {I:(DE-He78)G105-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30161022},
      pmc          = {pmc:PMC6349460},
      doi          = {10.1200/JCO.2018.78.4777},
      url          = {https://inrepo02.dkfz.de/record/148599},
}