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| By
Heather Lindsey |
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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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