Smoking Significantly Associated With Colorectal Cancer Incidence and Mortality  CME/CE

News Author: Roxanne Nelson
CME Author: Hien T. Nghiem, MD
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December 17, 2008 — Cigarette smoking is significantly linked to both incidence and mortality of colorectal cancer, according to the results of a new meta-analysis published in the December 17 issue of the Journal of the American Medical Association.

Edoardo Botteri, MSc, of the European Institute of Oncology in Milan, Italy, and colleagues found that cigarette smoking was associated with an absolute risk increase of 10.8 cases per 100,000 person-years and a statistically significant dose relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking.

"Smoking has not been considered so far in the stratification of individuals for CRC [colorectal cancer] screening," the study authors write. "However, several studies reported that CRC occurs earlier in smokers, particularly in those with heavy tobacco consumption, and our previous and present findings provide strong evidence of the detrimental effect of cigarette smoking on the development of adenomatous polyps and CRC."

"We believe that smoking represents an important factor to consider when deciding on the age at which CRC screening should begin, either by lowering the age in smokers or increasing the age in nonsmokers," they write.

Link With Tobacco Remains Controversial

Tobacco has been responsible for an estimated 100 million deaths during the past century, but globally, approximately 1.3 billion individuals continue to smoke. Although smoking has been strongly associated with a wide range of malignant tumors, the link between tobacco and colorectal cancer remains controversial.

Both esophageal and gastric cancers have been strongly associated with tobacco use, but the association with colorectal cancer is less defined. A number of large cohort studies have suggested a link between colorectal cancer and smoking, and the study authors note that a recent meta-analysis by their own team showed that smoking doubles the risk for colorectal polyps, which are established precursors for a subsequent malignant tumor.

However, other papers have not detected a significant relationship between smoking and colorectal cancer, an inconsistency that might be partially explained by variations in study design, characteristics of the study cohort, and the heterogeneous treatment of the most likely confounders.

The current meta-analysis was conducted to clarify the association of cigarette smoking and colorectal cancer, the study authors explain. Another objective was to study the dose-response patterns of tobacco exposure on the risk for colorectal cancer.

Smoking Associated With Increased Incidence

The researchers ultimately included 106 observational studies in the analysis of incidence, which were conducted globally from 1969 to 2008. The pooled relative risk (RR) for current smokers vs never-smokers and former smokers vs never-smokers was 1.07 (95% confidence interval [CI], 0.99 - 1.16) and 1.17 (95% CI, 1.11 - 1.22).

They observed a linear increase in risk as the amount of cigarettes smoked increased. The risk for colorectal cancer increased by 7.8% for every additional 10 cigarettes smoked per day, or by 4.4 for every additional 10 pack-years. As an example, a person who smoked 1 pack a day for 50 years or 2 packs per day for 25 years had a 24% higher risk for the development of colorectal cancer vs a never-smoker.

Smoking Associated With an Increase in Mortality Rates

The researchers included 17 English-language cohort studies, published between 1990 and 2008, in their analysis of smoking and the risk for colorectal cancer mortality. Based on 14 of these studies, the RR for current smokers vs never-smokers was 1.28 (95% CI, 1.15 - 1.42), whereas the RR for former smokers vs never-smokers was 1.23, based on data from 12 studies.

The absolute annual rates of colorectal cancer–related mortality was 41.3 deaths per 100,000 in smokers and 35.3 per 100,000 in nonsmokers, corresponding to an absolute increased risk of 6.0 deaths per 100,000 person-years. They also noted a linear increase in mortality risk that coincided with an increasing number of cigarettes per day smoked. This risk increased by 7.4% and 10.6%, for ever-smokers and current smokers. The risk also increased by 9.5% for every additional 10 years of smoking.

For both incidence and death, the association was stronger for cancer of the rectum vs the colon. Also, although this analysis found a statistically significant excess risk for colorectal cancer among smokers, the researchers write that the magnitude of the association is lower vs previously observed for adenomas.

The study authors have disclosed no relevant financial relationships.

JAMA. 2008;300:2765-2778.

Clinical Context

Despite the number of deaths from tobacco use, there is still an estimated 1.3 billion smokers in the world. Smoking-related cancers are not only frequent in the lung, oropharynx, and larynx but also in organs such as the kidney, bladder, cervix, lower urinary tract, and pancreas. With respect to the digestive system, esophageal and gastric cancers have been strongly associated with tobacco use, whereas the link between smoking and colorectal cancer remains controversial. Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. The association between cigarette smoking and colorectal cancer has been inconsistent among studies. The inconsistency among studies could be explained by different study designs; population characteristics; and the heterogeneous treatment of the most likely confounders, such as diet, alcohol, physical activity, and body mass index.

The aim of this study was to clarify the association of cigarette smoking and colorectal cancer through a comprehensive search of the literature and a meta-analysis of observational studies considering both incidence and mortality rates.

Study Highlights

• In this study, the investigators performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE through May 2008, with no restrictions. In addition, they reviewed references from all retrieved articles.
• All articles were independent and contained the minimal information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty.
• Articles were reviewed and data were extracted and crosschecked independently by 3 investigators, and any disagreement was resolved by consensus among all 3.
• Results demonstrated that 106 independent observational studies were included in the analysis of incidence.
• Overall, the meta-analysis is based on a total of 39,779 incident cases.
• 26 studies provided adjusted risk estimates for ever-smokers vs never-smokers, leading to a pooled relative risk of 1.18 (95% CI, 1.11 - 1.25).
• Smoking was associated with an absolute risk increase of 10.8 cases per 100,000 person-years (95% CI, 7.9 - 13.6).
• Studies demonstrated a statistically significant dose relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking.
• The risk increased by 7.8% (95% CI, 5.7% - 10.0%) for every additional 10 cigarettes per day or by 4.4% (95% CI, 1.7% - 7.2%) for every additional 10 pack-years.
• 3 studies reported a higher risk for microsatellite-unstable tumors vs microsatellite-stable tumors when comparing current smokers vs never-smokers.
• 17 cohort studies were included in the analysis of mortality rates. The pooled risk estimate for ever-smokers vs never-smokers was 1.25 (95% CI, 1.14 - 1.37).
• Smoking was associated with an absolute risk increase of 6.0 deaths per 100,000 person-years (95% CI, 4.2 - 7.6).
• A linear increase in the risk for colorectal cancer mortality was also observed with increasing number of cigarettes smoked per day and duration of smoking.
• For both incidence and mortality rates, the association was stronger for cancer of the rectum vs the colon.
• Limitations to this study included the heterogeneity of the studies in regard to adjustments of the estimates for potential confounders, such as diet, body mass index, alcohol consumption, and physical activity, which limit the generalization of the results.

Pearls for Practice

• Smoking-related cancers are not only frequent in the lung, oropharynx, and larynx, but are also common in organs such as the kidney, bladder, cervix, lower urinary tract, and pancreas. In addition, esophageal and gastric cancers have been strongly associated with tobacco use.
• Cigarette smoking is significantly associated with colorectal cancer incidence and mortality.

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