[MOL] Alcohol and cigarettes increase p53 mut5ations in NSCLC [02563] Medicine On Line


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[MOL] Alcohol and cigarettes increase p53 mut5ations in NSCLC



Journal Summary
Alcohol and Cigarettes Increase Occurrence of p53 Mutations in Non-Small Cell Lung Cancer
  
 
 
By Heather Lindsey
 

Researchers at Johns Hopkins University have found that alcohol consumption and smoking together increase the frequency of p53 mutations in non-small cell lung cancer (NSCLC). Alcohol may enhance the p53 genetic mutation rate caused by tobacco in the lungs. Loss of p53 function in a clonal population of cells provides a growth advantage that may result in cancer progression.

 
The investigators studied 105 patients (95 smokers and 10 nonsmokers) with NSCLC undergoing surgery for the disease.

Ninety-seven patients provided an alcohol intake history. Forty-four percent drank one or more drinks per day, 21 percent drank less than one drink per day and 35 percent did not drink. Nonsmokers had smoked fewer than 100 cigarettes during their lifetime, and smokers had at least a 10-pack-year history of smoking.

Sequence analysis of p53 was performed on tumor samples from the 105 patients using direct sequencing and the p53 GeneChip. At least one mutation was found in 53 percent of these tumors.

P53 mutations occurred in 72 percent of patients who drank one or more drinks daily, while the mutations occurred in 39 percent of those who drank less than one drink daily (P = 0.003; values less than 0.05 are considered significant). Fifty-eight percent of smokers versus 10 percent of nonsmokers carried p53 mutations (P = 0.02).

Seventy-six percent of patients who drank one or more drinks per day and smoked had p53 mutations in their lung tumors, while 42 percent of patients who drank less than one drink per day and smoked had p53 mutations. Only 14 percent of people who neither drank nor smoked had tumors with p53 mutations.

GC to TA transversions were the most common p53 mutation seen in smokers. Only one p53 mutation was present among the 10 nonsmokers. GC to AT transitions were more common in drinkers than non-drinkers, although this was not statistically significant.

P53 mutations may be associated with the progression of NSCLC, noted the researchers. In addition, these mutations may be linked to more aggressive NSCLC and shorter survival.

Alcohol Consumption and Cigarette Smoking Increase the Frequency of p53 Mutations in Non-Small Cell Lung Cancer. Steven A. Ahrendt, John T. Chow, Stephen C. Yang, Li Wu, Mei-Jie Zhang, Jin Jen and David Sidransky. Cancer Research 60 (June 15, 2000), 3155-3159.


 
 
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