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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-1-29
pubmed:abstractText
Inactivation of the FANC-BRCA pathway via promoter methylation of the FANCF gene renders cells sensitive to DNA crosslinking agents, and has been identified in ovarian cancer cell lines and sporadic primary tumor tissues. We investigated epigenetic alterations in the FANC-BRCA pathway in head and neck squamous cell carcinomas (HNSCC) and non-small-cell lung cancers (NSCLC) using methylation-specific PCR. Promoter methylation of FANCF occurred in 15% (13/89) of HNSCCs and 14% (22/158) of NSCLCs. Methylation of BRCA1 occurred only in 6/158 NSCLC, and was limited to adenocarcinomas and large-cell carcinomas of the lung. No methylation of BRCA2 was detected. FANCF methylation was associated with a shorter duration of tobacco use (P=0.03) and a younger age of starting smoking (P=0.06) in NSCLC, and with a greater number of years of alcohol drinking (P=0.02) in HNSCC. In adenocarcinomas of the lung, FANCF promoter methylation was a significant predictor of poor survival with a hazard ratio of 3.1 (95% CI 1.2-7.9). This study demonstrates that inactivation of the FANC-BRCA pathway is relatively common in solid tumors and may be related to tobacco and alcohol exposure and survival of these patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1000-4
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14647419-Aged, pubmed-meshheading:14647419-Alcohol Drinking, pubmed-meshheading:14647419-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:14647419-Carcinoma, Squamous Cell, pubmed-meshheading:14647419-Cell Cycle Proteins, pubmed-meshheading:14647419-DNA Methylation, pubmed-meshheading:14647419-DNA-Binding Proteins, pubmed-meshheading:14647419-Fanconi Anemia Complementation Group Proteins, pubmed-meshheading:14647419-Genes, BRCA1, pubmed-meshheading:14647419-Genes, BRCA2, pubmed-meshheading:14647419-Humans, pubmed-meshheading:14647419-Lung Neoplasms, pubmed-meshheading:14647419-Male, pubmed-meshheading:14647419-Middle Aged, pubmed-meshheading:14647419-Mouth Neoplasms, pubmed-meshheading:14647419-Nuclear Proteins, pubmed-meshheading:14647419-Promoter Regions, Genetic, pubmed-meshheading:14647419-Proteins, pubmed-meshheading:14647419-Smoking, pubmed-meshheading:14647419-Survival Analysis
pubmed:year
2004
pubmed:articleTitle
Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival.
pubmed:affiliation
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.