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Background  The analysis of relationships of BRCA alterations with cancer at sites other than breast/ovary may provide innovative information concerning BRCA pathogenic role and support additional clinical decisions. Aim of this study is to compare presence of cancers in other sites in members of hereditary (H) and not-hereditary (nH) branches of families of patients eligible to BRCA test.    Methods  We retrospectively analyzed the incidence of cancer in other sites in members of 136 families eligible for hereditary breast/ovarian cancer genetic counseling at Centro Studi Tumori Eredo-familiari of our Institute; we compared the frequency of other cancer types in 1156 members of the H-branch with respect to 1062 members of nH-Branch. The families belonging to a proband case and with informative members in at least three generation entered the present study.    Results  The frequency of other Cancers in members of H-branch was significantly higher than that in members of nH-branch (161 vs 75 cancers;  p  < 0.0001). In specific, members of H-branch had a significantly higher probability to have more lung cancer (38 vs 9; p  < 0.0006), kidney cancer (23 vs 5; p  < 0.0005), liver cancer (13 vs 3; p  < 0.02) and larynx cancer (14 vs 4; p  < 0.03). Interestingly, to belong to H-branch resulted significantly associated with a higher probability of lung cancer (OR 4.5; 2.15–9.38 95%C.I.), liver cancer (OR: 4.02; 1.14–14.15 95% C.I.) and larynx cancer (OR:3.4; 1.12–10.39 95%C.I.) independently from Gender and Age.    Conclusions  Members belonging to the H-branch of families of patients eligible to BRCA test have a higher risk of tumors in lung, larynx and liver. Clinicians should consider the increased risk for these cancers to activate prevention/early diagnosis practices in members of families with breast/ovarian familial cancer syndrome.

Hereditary and non-hereditary branches of family eligible for BRCA test: cancers in other sites