Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry

Matilde E. Lleonart, Gregory D. Kirk, Stephanie Villar, Olufunmilayo A. Lesi, Abhijit Dasgupta, James J. Goedert, Maimuna Mendy, Monica C. Hollstein, Ruggero Montesano, John D. Groopman, Pierre Hainaut, Marlin D. Friesen

Research output: Contribution to journalArticlepeer-review

Abstract

A mutation in codon 249 of the TP53 gene (219Ser), related to aflatoxin B1 exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249Ser-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249Ser (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P < 0.05). About half (52%) of the hepatocellular carcinoma cases had >2,500 copies of 249Ser/mL plasma, corresponding to the prevalence of this mutation in liver tumors in The Gambia. In comparison, only 15% of control group and 26% of cirrhotic participants exceeded this level (P < 0.05). Further subset analysis revealed a statistically significant, quantitative relation between diagnosis of hepatocellular carcinoma and levels of 249Ser detected at 2,501 to 10,000 copies/mL plasma (odds ratio, 3.8; 95% confidence interval, 1.3-10.9) and at > 10,000 copies/mL plasma (odds ratio, 62; 95% confidence interval, 4.7-820) when compared with control subjects and after adjusting for age, gender, recruitment site, hepatitis B and C serologic status, and total DNA concentration. Levels of > 10,000 copies of 249Ser/mL plasma were also significantly associated with the diagnosis of hepatocellular carcinoma (odds ratio, 15; 95% confidence interval, 1.6-140) when compared with cirrhotic patients. Potential applications for the quantification of 249Ser DNA in plasma include estimation of long-term, cumulative aflatoxin exposure and selection of appropriate high-risk individuals for targeted intervention.

Original languageEnglish (US)
Pages (from-to)2956-2962
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number12
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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