Cigarette smoking increases risk for CRC
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The risk for colorectal cancer increased with cigarette smoking, according to a study published in the American Journal of Gastroenterology.
“The association is driven by the selective effect of smoking on the risk of CRC developing through the [microsatellite] pathway,” Edoardo Botteri, PhD, from the section for colorectal cancer screening at the Cancer Registry of Norway, Oslo, and colleagues wrote. “Our findings support smoking cessation to reduce the risk of CRC. Further evaluations of the molecular mechanisms through which smoking affects colorectal carcinogenesis are warranted.”
Botteri and colleagues performed a systematic review and metanalysis of 188 studies on the correlation between cigarette smoking and CRC. Investigators calculated the relative risk of CRC regarding smoking status, intensity, duration, packing-years and time since quitting.
Results showed the pooled RR for CRC was 1.14 (95% CI, 1.1–1.18) for current smokers and 1.17 (95% CI, 1.15–1.2) for former smokers compared with nonsmokers. Investigators noted the risk for CRC increased linearly with smoking intensity and duration.
“Former smokers who had quit smoking for more than 25 years had significantly decreased risk of CRC compared with current smokers,” the investigators wrote.
According to researchers, smoking was significantly correlated with the risk for CRC. This was characterized by high CpG island methylator phenotype (RR = 1.42; 95% CI, 1.2–1.67; number of studies [n] = 4), BRAF mutation (RR = 1.63; 95% CI, 1.23–2.16; n = 4), or high microsatellite instability (RR = 1.56; 95% CI, 1.32–1.85; n = 8). However, it was not characterized by KRAS (RR = 1.04; 95% CI, 0.9–1.2; n=55) or TP53 (RR = 1.13; 95% CI, 0.99–1.29; n=55) mutations.
“Regarding time since smoking cessation, we acknowledge that few studies attempted to adjust the analysis for smoking history measures, such as smoking duration and intensity,” Botteri and colleagues. “Thus, we cannot quantify how much the estimates for smoking cessation are influenced by those factors, and our findings should be considered with caution.”
Perspective
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Carole Macaron, MD
Growing evidence has linked cigarette smoking to colorectal cancer in recent years. Although the molecular mechanisms behind this association are not clearly understood, we know from epigenetic studies that smoking induces DNA methylation at CpG islands with strong dose-response associations between methylation, smoking exposure, and time since cessation of smoking. The current study findings that ever smokers had a higher risk for CIMP-positive (RR = 1.42), MSI-high (RR = 1.56), or BRAF mutated (RR = 1.63) colorectal cancers, compared with never smokers, is consistent with prior studies and indicates that smoking largely increases the risk for CRC through the microsatellite instability pathway.
While the estimated increased risk for CRC of 15% to 20% in men and women may seem marginal compared with the carcinogenesis effect of tobacco on other cancers, it is dose dependent. The current meta-analysis provides strong evidence that the risk increases linearly with the increasing duration and intensity of smoking. This means that the more packs of cigarettes smoked a year, the longer a person smoked, and the earlier they started smoking, the greater the risk for developing CRC. Even more, former smokers maintain that elevated risk for up to 25 years after quitting smoking, perhaps to reach the full DNA methylation recovery as suggested by some epigenome-wide association studies.
The dose dependent association, the persistent carcinogenic impact of cigarettes years after quitting smoking and the preventable effect of cigarettes smoking on CRC are key messages to be shared with the 34 million American adults who still smoke cigarettes today.
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