p53 mutations in esophageal tumors from a high incidence area of China in relation to patient diet and smoking history.
Esophageal tumors from 29 patients residing in Guangzhou, China were examined for mutations in exons 5-8 of the p53 tumor suppressor gene and for p53 protein accumulation in tumor cell nuclei. Anamnestic data for each patient, which included information on family history of cancer, tobacco smoking, drinking of alcoholic beverages, and dietary habits such as consumption of pickled vegetables, were recorded. Screening of DNA from tumor cells microdissected from biopsies was performed by PCR amplification of p53 gene exons 5-8, denaturing gradient gel electrophoresis analysis, and DNA sequencing. Mutations were identified in 20 of 29 tumors (69%). All tumors harboring a missense mutation in the p53 gene also showed nuclear accumulation of the tumor suppressor protein by immunohistochemistry. The most common p53 mutations in these tumors were guanine to adenine (G-->A) transitions (10 of 20 tumors; 50%). We did not find multiple mutations at codon 176, in contrast to Lung et al. in their recent study of esophageal cancer patients from Guangzhou (M. L. Lung et al., Cancer Epidemiol. Biomark. Prev., 5: 277-284, 1996). The mutation prevalence was high both in smokers (13 mutations in 20 smokers; 65%) and in nonsmokers (7 of 9 tumors with mutations; 78%), an observation that differs from that of studies in European and North American patients, which demonstrate a much higher prevalence of p53 mutations in smokers than in nonsmokers (reviewed in R. Montesano et al., Int. J. Cancer Predict. Oncol., 69: 225-235, 1996.). Our findings in this pilot study of tumor suppressor gene mutations in patients from Guangzhou support a large body of epidemiological observations pointing to dietary mutagenic carcinogens peculiar to populations in China at high risk of esophageal cancer.
Bennett
W P
WP
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.
von Brevern
M C
MC
Zhu
S M
SM
Bartsch
H
H
Muehlbauer
K R
KR
Hollstein
M C
MC
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004032:Diet / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects