title: Smoking, gender, and ethnicity predict somatic BRAF mutations in colorectal cancer.
abstract: Approximately 5% to 15% of all colorectal cancers (CRC) have an activating BRAF somatic mutation, which may be associated with a distinct risk profile compared with tumors without BRAF mutations. Here, we measured the prevalence and epidemiologic correlates of the BRAF V600E somatic mutation in cases collected as a part of a population-based case-control study of CRC in northern Israel. The prevalence of BRAF V600E was 5.0% in this population, and the mutation was more likely to be found in tumors from cases who were of Ashkenazi Jewish descent [odds ratio (OR), 1.87; 95% confidence interval (95% CI), 1.01-3.47], female (OR, 1.97; P = 1.17-3.31), and older (73.8 years versus 70.3 years; P < 0.001). These results were similar when restricting to only tumors with microsatellite instability. Whether smoking was associated with a BRAF somatic mutation depended on gender. Although men were less likely to have a tumor with a BRAF somatic mutation, men who smoked were much more likely to have a tumor with a somatic BRAF mutation (OR(interaction), 4.95; 95% CI, 1.18-20.83) than women who never smoked. We note the strong heterogeneity in the reported prevalence of the BRAF V600E mutation in studies of different ethnicities, with a lower prevalence in Israel than other Western populations but a higher prevalence among Jewish than non-Jewish Israeli cases. Epidemiologic studies of CRC should incorporate somatic characteristics to fully appreciate risk factors for this disease.
authors.affiliation: Environmental Health Sciences, School of Public Health, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Rozek
authors.forename: Casey M
authors.initials: CM
authors.lastname: Herron
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology / Q000208:ethnology; D007585:Jews / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf