title: The APC I1307K allele conveys a significant increased risk for cancer.
abstract: This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate its use for specific cancer types-particularly in males. Female carriers have better prognosis and increased lifespan.
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Leshno
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shiran
authors.initials: S
authors.lastname: Shapira
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Liberman
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kraus
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Sror
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Amira
authors.initials: A
authors.lastname: Harlap-Gat
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Doran
authors.initials: D
authors.lastname: Avivi
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Galazan
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: David
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Department of Gastroenterology, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Nitsan
authors.initials: N
authors.lastname: Maharshak
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Serhan
authors.initials: S
authors.lastname: Moanis
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Department of Gastroenterology, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Nadir
authors.initials: N
authors.lastname: Arber
authors.affiliation: Integrated Cancer Prevention Center, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Department of Gastroenterology, Tel- Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Moshkowitz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D015995:Prevalence; D011379:Prognosis; D012306:Risk
keywords: I1307K; cancer risk; gender disparity; prognosis