Serum retinol and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.

Vitamin A (retinol) plays a key role in the regulation of cell growth and differentiation, and has been studied as a potential chemopreventive agent for prostate cancer. However, findings from epidemiologic studies on the association between circulating retinol concentrations and the risk of prostate cancer are inconsistent. We examined whether serum concentrations of retinol were associated with the risk of prostate cancer in a nested case-control study using 692 prostate cancer cases and 844 matched controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We estimated the risk of prostate cancer using multivariate, conditional logistic regression to calculate odds ratios and 95% confidence intervals for overall prostate cancer and aggressive disease (stage III or IV or Gleason >7; n = 269). Serum retinol concentrations were not associated with overall prostate cancer risk; however, the highest versus lowest concentrations of serum retinol were associated with a 42% reduction in aggressive prostate cancer risk (P(trend) = 0.02), with the strongest inverse association for high-grade disease (Gleason sum >7; odds ratio, 0.52; 95% confidence interval, 0.32-0.84; P(trend) = 0.01). Our results suggest that higher circulating concentrations of retinol are associated with a decreased risk of aggressive prostate cancer. Further research is needed to better understand the significance of elevations in serum retinol concentrations and the possible biological mechanisms through which retinol affects prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1227-31)

Seasonal Variation in TP53 R249S-Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection

Background: Chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are etiological factors for hepatocellular carcinoma (HCC) in countries with hot, humid climates. HCC often harbors a TP53 (tumor protein p53) mutation at codon 249 (R249S). In chronic carriers, 1762T/1764A mutations in the HBV X gene are associated with increased HCC risk. Both mutations have been detected in circulating cell-free DNA (CFDNA) from asymptomatic HBV carriers

Aflatoxin-Induced TP53 R249S Mutation in HepatoCellular Carcinoma in Thailand: Association with Tumors Developing in the Absence of Liver Cirrhosis

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3rd among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G→T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection

Sensitive and specific detection of K-ras mutations in colon tumors by short oligonucleotide mass analysis

Short oligonucleotide mass analysis (SOMA) is a technique by which small sequences of mutated and wild-type DNA, produced by PCR amplification and restriction digestion, are characterized by HPLC-electrospray ionization tandem mass spectrometry. We have adapted the method to specifically detect two common point mutations at codon 12 of the c-K-ras gene. Mutations in DNA from 121 colon tumor samples were identified by SOMA and validated by comparison with sequencing. SOMA correctly identified 26 samples containing the 12GAT mutation and four samples containing the 12AGT mutation. Sequencing did not reveal mutant DNA in three samples out of the 26 samples shown by SOMA to contain the 12GAT mutation. In these three samples, the presence of mutant DNA was confirmed by SOMA analysis after selective PCR amplification in the presence of BstN1 restriction enzyme. Additional mutations in codons 12 and 13 were revealed by sequencing in 24 additional samples, and their presence did not interfere with the correct identification of G to A or G to T mutations in codon 12. These results provide the basis for a sensitive and specific method to detect c-K-ras codon 12-mutated DNA at levels below 10–12% of wild-type DNA