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Smoking and Colorectal Cancer A Meta-analysis

Edoardo Botteri, MSc; Simona Iodice, MSc; Vincenzo Bagnardi, PhD; Sara Raimondi, MSc; Albert B. Lowenfels, MD; Patrick Maisonneuve, Eng
JAMA. 2008;300(23):2765-2778. doi:10.1001/jama.2008.839.
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Context 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.

Objective To clarify the association of cigarette smoking and colorectal cancer, we performed a comprehensive literature search and a meta-analysis of observational studies considering both incidence and mortality.

Data Sources We performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE to May 2008, with no restrictions. We also reviewed references from all retrieved articles.

Study Selection All articles that were independent and contained the minimum information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty.

Data Extraction Articles were reviewed and data were extracted and cross-checked independently by 3 investigators, and any disagreement was resolved by consensus among all 3.

Results One hundred six observational studies were included in the analysis of incidence. Twenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [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). We found 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. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever 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). For both incidence and mortality, the association was stronger for cancer of the rectum than of the colon.

Conclusion Cigarette smoking is significantly associated with colorectal cancer incidence and mortality.

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Figure 1. Flowchart of Selection of Studies for Inclusion in Meta-analysis
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Figure 2. Forest Plot for Colorectal Cancer Incidence: Adjusted Risk Estimates for Ever vs Never Smokers
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The size of each square is proportional to the study's weight (inverse of variance). The approximation of the estimates reported in the original studies could lead to asymmetrical confidence intervals (CIs). RR indicates relative risk.

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Figure 3. Dose-Response Relationship Between Relative Risk of Colorectal Cancer Incidence and Duration of Smoking
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The relationship is modeled by a second-order fractional polynomial (dark line). Model-based 95% confidence intervals are also reported (dashed lines). Circles present the duration-specific relative risk estimates reported in each study (>1 point estimate per study). The area of each circle is proportional to the precision (ie, inverse variance) of the relative risk. The dotted line represents the null hypothesis of no association. The vertical axis is on a log scale.

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Figure 4. Colorectal Cancer Mortality: Adjusted Risk Estimates for Ever vs Never Smokers
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The size of each square is proportional to the study's weight (inverse of variance). When the estimate for ever smokers was not reported, we plotted separate estimates for current and former smokers. CI indicates confidence interval; RR, relative risk.

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Figure 5. Colorectal Cancer Mortality Risk Estimates for Ever Smokers From 2 Large Cohort Studies Obtained at Different Follow-up Times
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US veterans study: references.6,3840 British doctors study: references.13,36,37 Error bars indicate 95% confidence intervals.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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