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Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations
  1. Luna Kadouri (luna{at}hadassah.org.il)
  1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
    1. Ayala Hubert (ayalah{at}hadassah.org.il)
    1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
      1. Yakir Rotenberg (ryakir{at}hadassah.org.il)
      1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
        1. Tamar Hamburger (tamarh{at}hadassah.org.il)
        1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
          1. Michal Sagi (msagi{at}hadassah.org.il)
          1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
            1. Chovav Nechushtan
            1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
              1. Dvorah Abeliovich (dvorah{at}cc.huji.ac.il)
              1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel
                1. Tamar Peretz (tamarp{at}cc.huji.ac.il)
                1. Hebrew University-Hadassah Medical Center, Jerusalem, Israel

                  Abstract

                  Abstract: Background: The risks for cancers other than breast (BC) or ovarian cancer (OC) in BRCA1/2 mutation carriers were elevated in studies of carrier families. However, case control studies did not confirm this observation.

                  Objective: To compare other cancers risks in BRCA1/2 mutation carriers and non-carriers all affected with BC and/or OC. Both groups share risk modifiers of BC/OC, which enable us to assess the role of BRCA1/2 mutations.

                  Methods: 1098 Ashkenazi Jewish women affected with BC and/or OC were ascertained during 1995-2003, molecular testing revealed 229 BRCA1 and 100 BRCA2 carriers and 769 non-carriers. COX proportional hazard models were used to evaluate the risk of other cancers. Analyses were conducted including all other cancers or only those diagnosed after BC/OC diagnosis.

                  Results: The hazard ratio (HR) for any other cancer were 2.6 (95%CI 1.7-4.2, p<0.001) and 1.8 (95%CI 0.95-3.6, p=0.07) in BRCA1 and BRCA2 carriers, respectively. The corresponding colon cancer HRs were 3.9 (95%CI 1.3-12.1, p=0.02) and 2.3 (95% CI 0.5-11.3, p=0.3) in BRCA1 and BRCA2 carriers. Lymphoma HR was 11.9 (95%CI 3.1-46.2, p=0.001) in BRCA2 carriers. Risk estimates for other cancers after BC/OC onset were similar.

                  Conclusion: We found a 2.5-fold increase in any other cancer and a 4-fold of colon cancer risk among BRCA1 carriers. Corresponding HRs in BRCA2 carriers were non-significant, except for markedly elevated lymphoma risk. Our results suggest a role for BRCA1/2 mutations in colorectal cancer risk in a subgroup of BC/OC affected carriers.

                  • BRCA1
                  • BRCA2
                  • cancer risk
                  • colon cancer

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