Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-8
pubmed:abstractText
Hepatocellular carcinoma (HCC) has a high mortality in East Asia and Sub-Saharan Africa, two regions where the main etiologic factors are chronic infections with hepatitis B virus and dietary exposure to aflatoxin. A single base substitution at the third nucleotide of codon 249 of TP53 (R249S) is common in HCC in these regions and has been associated with aflatoxin-DNA adducts. To determine whether R249S may be detected in plasma DNA before HCC diagnosis, we conducted a case-control study nested in a cohort of adult chronic hepatitis B virus carriers from Qidong County, People's Republic of China. Of the 234 plasma specimens that yielded adequate DNA, only 2 (0.9%) were positive for R249S by restriction fragment length polymorphisms, and both of them were controls. Of the 249 subjects tested for aflatoxin-albumin adducts, 168 (67%) were positive, with equal distribution between cases and controls. Aflatoxin-albumin adduct levels were low in the study, suggesting an overall low ongoing exposure to aflatoxin in this cohort. The R249S mutation was detected in 11 of 18 (61%) available tumor tissues. To assess whether low levels of mutant DNA were detectable in pre-diagnosis plasma, 14 plasma specimens from these patients were analyzed by short oligonucleotide mass analysis. Nine of them (64%) were found to be positive. Overall, these results suggest that HCC containing R249S can occur in the absence of significant recent exposure to aflatoxins. The use of short oligonucleotide mass analysis in the context of low ongoing aflatoxin exposure may allow the detection of R249S in plasma several months ahead of clinical diagnosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1638-43
pubmed:meshHeading
pubmed-meshheading:19366907-Adult, pubmed-meshheading:19366907-Aflatoxins, pubmed-meshheading:19366907-Albumins, pubmed-meshheading:19366907-Carcinoma, Hepatocellular, pubmed-meshheading:19366907-Carrier State, pubmed-meshheading:19366907-China, pubmed-meshheading:19366907-Cocarcinogenesis, pubmed-meshheading:19366907-Codon, pubmed-meshheading:19366907-Female, pubmed-meshheading:19366907-Food Contamination, pubmed-meshheading:19366907-Genotype, pubmed-meshheading:19366907-Hepatitis B, Chronic, pubmed-meshheading:19366907-Humans, pubmed-meshheading:19366907-Liver Neoplasms, pubmed-meshheading:19366907-Logistic Models, pubmed-meshheading:19366907-Male, pubmed-meshheading:19366907-Middle Aged, pubmed-meshheading:19366907-Mutation, pubmed-meshheading:19366907-Polymorphism, Restriction Fragment Length, pubmed-meshheading:19366907-Tumor Suppressor Protein p53
pubmed:year
2009
pubmed:articleTitle
TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China.
pubmed:affiliation
IARC, Lyon Cedex 08, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural