title: The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers.
abstract: Cancer risks in heterozygous mutation carriers of the ATM, BLM, and FANCC genes are controversial. To shed light on this issue, cancer rates were evaluated by cross referencing asymptomatic Israeli heterozygous mutation carriers in the ATM, BLM, and FANCC genes with cancer diagnoses registered at the Israeli National Cancer Registry (INCR). Comparison of observed to expected Standardized Incidence Rates (SIR) was performed. Overall, 474 individuals participated in the study: 378 females; 25 Arab and 31 Jewish ATM carriers, 152 BLM carriers, and 170 FANCC carriers (all Ashkenazim). Age range at genotyping was 19-53 years (mean + SD 30.6 + 5 years). In addition, 96 males were included; 5, 34, and 57 ATM, BLM, and FANCC mutation carriers, respectively. Over 5-16 years from genotyping (4721 person/years), 15 new cancers were diagnosed in mutation carriers: 5 breast, 4 cervical, 3 melanomas, and one each bone sarcoma, pancreatic, and colorectal cancer. No single cancer diagnosis was more prevalent then expected in all groups combined or per gene analyzed. Specifically breast cancer SIR was 0.02-0.77. We conclude that Israeli ATM, BLM, and FANCC heterozygous mutation carriers are not at an increased risk for developing cancer.
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Laitman
authors.affiliation: Israel National Cancer Registry (INCR), Ministry of Health, Jerusalem, Israel; School of Public Health, Haifa University, Haifa, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Boker-Keinan
authors.affiliation: Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Berkenstadt
authors.affiliation: Israel National Cancer Registry (INCR), Ministry of Health, Jerusalem, Israel.
authors.forename: Irena
authors.initials: I
authors.lastname: Liphsitz
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.affiliation: Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Ries-Levavi
authors.affiliation: National AT Clinic, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Ifat
authors.initials: I
authors.lastname: Sarouk
authors.affiliation: Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: eitan.friedman@sheba.health.gov.il.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D053484:RecQ Helicases / Q000235:genetics*; D012306:Risk; D055815:Young Adult
chemical_list: C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C097151:Bloom syndrome protein; D053484:RecQ Helicases
keywords: ATM; BLM; Cancer risks; FANCC; autosomal recessive; founder mutations; inherited cancer syndrome