Frequent Epigenetic Silencing of the p16 Gene in Non‐small Cell Lung Cancers of Tobacco Smokers

• DOI: 10.1111/j.1349-7006.2002.tb01212.x
• Publication Date: 2005-08-22T10:39:13Z
• Authors: Naoki Yanagawa; Gen Tamura; Hiroyuki Oizumi; Nobumasa Takahashi; Yasuhisa Shimazaki; Teiichi Motoyama
• Keywords: Male; Lung Neoplasms; Genes, p16; Smoking; Loss of Heterozygosity; DNA Methylation; Middle Aged; Article; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Humans; Female; Gene Silencing; Chromosomes, Human, Pair 9; Promoter Regions, Genetic; Aged

Epidemiological studies have demonstrated a causal link between tobacco smoking and lung cancer. We investigated the association inactivation of p16 gene in 51 non-small cell cancers (NSCLCs). Aberrations were studied by PCR single-strand conformation polymorphism analysis, followed direct sequencing, microsatellite methylation-specific PCR, immunohistochemistry. Mutations detected 3.9% (2/51) tumors; tumors carrying mutations from smokers. The incidences loss heterozygosity, homozygous deletion, promoter methylation 37 smokers vs. 14 non-smokers were; 45.9% 28.6%, 16.2% 7.1%, 35.1% respectively. Among these, only was statistically significant (P < 0.05). Therefore, epigenetic aberration is considered to be major causative event silencing smoking. Loss protein expression apparent 49% (25/51) tumors, associated with 0.05) histological type These findings suggest that leads mainly through mechanism, ultimately increasing risk NSCLC, especially squamous type.