Original article—alimentary tract
Cigarette Smoking and Colorectal Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition Study

https://doi.org/10.1016/j.cgh.2010.10.012Get rights and content

Background & Aims

There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location.

Methods

We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06–1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08–1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% CI, 0.98–1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04–1.50) and current smokers (HR, 1.31; 95% CI, 1.06–1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P = .45) for former smokers and a significant difference for current smokers (P = .02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers.

Conclusions

Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.

Section snippets

Population

EPIC is a multicenter prospective cohort study designed to investigate the relationship between diet, nutritional and metabolic characteristics, lifestyle factors, and risk of cancer. Enrollment of individuals took place between 1991 and 2000 in 23 collaborating centers in 10 European countries (Denmark, France, Germany, Greece, Italy, The Netherlands, Norway, Spain, Sweden, and the United Kingdom). Subjects were mostly selected from the general population of a specific geographic area.

Results

Our analyses were based on 2741 CRC cases (1058 men, 1683 women), of which 950 had rectal cancer (44.8% men) and 1791 colon cancer (766 proximal tumors [34.5% men], 772 distal tumors [38.6% men], and 253 colon tumors unspecified in location [27.7% men]). Mean follow-up time was 8.7 years. Baseline characteristics stratified by smoking status are shown in Table 1.

Ever smokers were at an increased risk of developing CRC (HR, 1.14; 95% CI, 1.04–1.24) and colon cancer (HR, 1.18; 95% CI, 1.06–1.32),

Discussion

Our results show that smokers are at an increased risk of colon cancer, which appears to be more pronounced in the proximal colon. Only when smoking was ceased for ≥20 years and, consequently, smoking duration was shorter, colon cancer risk was found to be similar to that of never smokers.

Several case-control studies have reported inconsistent results on whether a specific part of the colon or rectum is more sensitive to the effect of smoking.4, 6, 7 In a recent cohort study in women in Norway,

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by the European Commission: Public Health and Consumer Protection Directorate (1993–2004); Research Directorate-General 2005; Ligue contre le Cancer, Societé 3M, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health, the participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Hellenic Ministry of Health, the Stavros Niarchos Foundation and the Hellenic Health Foundation (Greece); Italian Association for Research on Cancer, National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (The Netherlands), Statistics Netherlands; Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane (Sweden); The Norwegian Research Council and NordForsk (Norway).

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