Abstract
1 min read<div>Abstract<p>In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. <i>KRAS2</i> mutations were detected by mutant-enriched PCR and sequencing (<i>n</i> = 1,098). <i>TP53</i> mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (<i>n</i> = 550). <i>KRAS2</i> or <i>TP53</i> mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had <i>KRAS2</i> mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had <i>TP53</i> mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between <i>TP53</i> mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of <i>TP53</i> or <i>KRAS2</i> mutations in the plasma of healthy subjects in a prospective study, suggesting that <i>KRAS2</i> mutation is detectable ahead of bladder cancer diagnosis. <i>TP53</i> mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis. (Cancer Res 2006; 66(13): 6871-6)</p></div>
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