Risk of colorectal adenoma is up in smokers.
The smoking-associated risk described in the report, a meta-analysis of 42 studies, indicates that a person who has smoked two packs per day for 25 years has almost twice the risk (relative risk, 1.88) of having a colorectal adenoma as a person who has never smoked, reported Mr. Botteri of the division of epidemiology and biostatistics at the European Institute of Oncology, Milan, and his colleagues.
The meta-analysis also indicated that the association between smoking and adenomatous polyps was stronger for high-risk adenomas than for low-risk adenomas. That finding contradicts some previous observations, made based on single studies, and suggests that smoking probably is associated with a higher risk of colon cancer. In the past, this question has been unresolved, the authors said (Gastroenterology 2008;134:388-95).
The investigators began by conducting a search of the PubMed database for relevant studies, and then scanned the references of the studies they reviewed to identify any studies they might have missed.
In total they identified 125 studies worthy of review, of which 42 were either independent case-control or nested case-control studies that met the criteria for inclusion in the meta-analysis. Twenty-six of those studies used colonoscopy or sigmoidoscopy plus barium enema and x-ray to view the entire colon. Sixteen studies used only sigmoidoscopy and did not view the entire colon.
After they pooled the data from the studies, the investigators found that current smokers had a relative risk for colorectal adenoma of 2.14, compared with never smokers. The pooled estimate for former smokers versus never smokers was a relative risk of 1.47, and the pooled estimate for ever smokers versus never smokers was a relative risk of 1.82.
When the investigators analyzed the data from a dose-response point of view, assuming a linear increase in risk, they found a 13% increased risk of presenting with adenomatous polyps for every additional 10 pack-years smoked, relative to never smokers.
The authors noted that they found the lowest relative risk between ever smokers and never smokers in the 20 studies conducted in the United States (a relative risk of 1.65), an intermediate risk in the 12 studies conducted in Europe (relative risk of 1.80), and the highest risk in the 7 studies conducted in Asia (relative risk of 2.18). Studies from Israel, Australia, and South America were excluded from this part of the analysis; there was one study from each of these regions.
These differences might suggest different smoking-cessation patterns across the continents, the investigators wrote.
Eleven of the studies recorded stratification of polyps as low risk or high risk. Although the definitions varied somewhat, the investigators concluded that the risk of developing high-risk adenomas was greater than the risk of developing low-risk adenomas for all classes of smokers, reaching statistical significance with a relative risk for current smokers of 2.04 and a relative risk for ever smokers of 2.10.
Smoking has not been shown consistently to be associated with colorectal cancer as yet. However, this may be because the latency period to cancer is so long--long enough that it is beyond the duration of the studies conducted, Mr. Botteri and his colleagues said.
Their meta-analysis also suggests another explanation: Control subjects in the studies, who are often unscreened or incompletely screened, may have undetected polyps initially, the authors added. That would tend to reduce the difference detected by the study.
Because of the lack of studies showing a clear-cut association between smoking and colon cancer, screening guidelines do not currently stratify individuals based on smoking history. However, this metaanalysis suggests that the guidelines should take smoking into account, Mr. Botteri and colleagues said.
"The results of this meta-analysis demonstrate that smokers are at higher risk which should be considered in developing screening policies," they wrote.
BY TIMOTHY F. KIRN