Smoking, Gender, and Ethnicity Predict Somatic BRAF Mutations in Colorectal Cancer
Open Access
- 1 March 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 19 (3), 838-843
- https://doi.org/10.1158/1055-9965.epi-09-1112
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 (ORinteraction, 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. Cancer Epidemiol Biomarkers Prev; 19(3); 838–43Keywords
This publication has 33 references indexed in Scilit:
- Clinicopathological and protein characterization of BRAF‐ and K‐RAS‐mutated colorectal cancer and implications for prognosisInternational Journal of Cancer, 2009
- Activated BRAF targets proximal colon tumors with mismatch repair deficiency and MLH1 inactivationGenes, Chromosomes and Cancer, 2003
- Phenotype of Microsatellite Unstable Colorectal Carcinomas: Well-Differentiated and Focally Mucinous Tumors and the Absence of Dirty Necrosis Correlate With Microsatellite InstabilityThe American Journal of Surgical Pathology, 2003
- DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular studyThe Lancet, 2002
- Mutations of the BRAF gene in human cancerNature, 2002
- Evidence for an age‐related influence of microsatellite instability on colorectal cancer survivalInternational Journal of Cancer, 2002
- Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.2001
- Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer.2001
- Ethnic differences in colorectal cancer among Arab and Jewish neighbors in IsraelThe American Journal of Gastroenterology, 2001
- Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotypeProceedings of the National Academy of Sciences of the United States of America, 2000