The Association Between Cigarette Smoking and Risk of CRC: Prospective Study
The association between cigarette smoking and the development of precancerous colorectal (CRC) adenomatous polyps has been proven in several clinical studies; however, the US Surgeon General has not declared cigarette smoking as a causative agent for (CRC).1 Hannan and colleagues2 examined the association between cigarette smoking and risk of incident CRC during 13 years of follow-up of a large prospective cohort in which individuals had initiated smoking an average of 44 years prior to enrollment. Analyses were based on updated individual level information on smoking status, duration, intensity, time since cessation, and age at cessation, with adjustment for 13 covariates which could confound the relationship.
Study Details
Participants were drawn from the Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective study of cancer incidence and mortality among 184,187 men and women from the United States. Members of the Nutrition Cohort completed baseline questionnaires at the time of enrollment in the CPS-II study (1992) as well as follow-up questionnaires in 1997, 1999, 2001, 2003, and 2005. Cigarette smoking status (“never”, “former”, “current”) was ascertained at enrollment in 1992/1993, and was updated in successive questionnaires.
A total of 86,402 men and 97,785 women participated in the Nutrition Cohort. After accounting for all exclusions, 51,365 men and 73,386 women were included in the analysis for the Hannan et al study.2
Multivariate models were adjusted for CRC risk factors:
- Body mass index
- Educational attainment
- Family history of CRC
- Physical activity
- Race
- Multivitamin use
- Aspirin use
- Alcohol use
- Vegetable consumption
- Red and processed meat consumption
- History of colorectal endoscopy
Results
A total of 1,962 verified incident cases of invasive CRC (1,006 men, 956 women) were identified between the time of enrollment in 1992/1993 and June 30, 2005.
- The incidence of CRC was 30% higher in current than never smokers [hazard ratios (HR), 1.27; 95% confidence intervals (95% CI), 1.06-1.52] in analyses that combined men and women, and adjusted for all measured risk factors.
- The association was weaker, although still statistically significant, among former smokers (HR, 1.23; 95% CI, 1.11-1.36).
- The association with former smoking seemed similar for cancers of the colon (HR, 1.19; 95% CI, 1.06-1.34) and rectum (HR, 1.26; 95% CI, 1.02-1.55), whereas
- The association with current smoking seemed stronger for colon cancer (HR, 1.28; 95% CI, 1.04-1.57) than for rectal cancer (HR, 0.97; 95% CI, 0.63- 1.47).
Among current smokers, increasing levels of smoking duration seemed to be associated with increased risk of CRC (P trend = 0.052), with the association between current smoking and CRC strongest among those who had smoked for 50 or more years. In sex-specific models of current smokers, the highest risk among men was seen in individuals who had smoked for 50 or more years (HR, 1.43; 95% CI, 0.99-2.07), and in women who had smoked for 40 to 49 years (HR, 1.56; 95% CI, 1.09-2.23).
Among former smokers, the association with CRC was limited to those who had quit at age 40 years or older and those with 30 or fewer years since cessation. Former smokers who had quit <10 years previously (HR, 1.48; 95% CI, 1.27-1.73) seemed to have the greatest risk, which was similar to the estimate observed among current smokers who had smoked for at least 50 years. Risk of CRC decreased with time since cessation (P trend = 0.0003), and earlier age at cessation (P trend = 0.0014). Similar trends were seen in sex-specific analyses.
Conclusions
The principal finding from this large cohort study is that long-term cigarette smoking was associated with an increased risk of CRC, even after adjusting for multiple covariates known to affect risk. One acknowledged limitation of the study was the lack of tumor samples to test for tumors with high microsatellite instability, which is more strongly associated with current smoking than tumors with low microsatellite instability.
Implications for Nursing Practice
Nurses working in primary care, gastroenterology, cancer prevention settings and cancer centers should continue to counsel patients on smoking cessation. Although the US Surgeon General has not declared smoking as a specific cause of CRC, the information in this study should be shared with patients and the general public as yet another reason to quit smoking.
References
- US DHHS, ed. The Health Consequences of Smoking: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office On Smoking and Health; 2004.
- Hannan LM, Jacobs EJ, Thun MJ. The Association between Cigarette Smoking & Risk of Colorectal Cancer in a Large Prospective cohort from the United States. Cancer Epidemiol Biomarkers Prev. 2009;18:3362-3367. doi:10.1158/1055-9965.EPI-09-0661 Abstract available at http://cebp.aacrjournals.org/content/18/12/3362.abstract
Smoking and Stage III Colon Cancer: Phase III Trial
Although cigarette smoking is well-known as a major risk factor for the development of lung and head and neck cancers, smoking is also implicated in the development of additional cancers, such as bladder cancer.1 Additionally, the development of colorectal cancer (CRC) is linked to cigarette smoking. Previous studies have shown that the risk for CRC in smokers is higher when patients have smoked for 20 years or more and for those who smoked earlier in life.2 A study of ethnically diverse participants in Hawaii demonstrated no significant risk between subsites of CRC and the number of pack-years smoked, but did note a difference in risk by type of tobacco, with non-filtered cigarettes and possibly cigars increasing both colon and rectal cancers.3 A recently published study in the journal Cancer discusses The Cancer and Leukemia Group B (CALGB) multicenter, phase 3 trial examined the impact of tobacco use on colon cancer recurrence among colon cancer survivors.4
Study Details
The authors prospectively collected lifetime smoking history from 1264 stage III colon cancer patients participating in a phase 3 trial via self-report questionnaires during and six months after completion of adjuvant chemotherapy
- Patients were randomized to receive bolus 5-fluoururacil/leucovorin (5-FU/LV) with or without irinotecan
- Smoking status was defined as never, current, or past
- Lifetime pack-years were defined as number of lifetime packs of cigarettes
- Patients were followed for recurrence or death
- The median follow-up time from completion of the first questionnaire was 5.3 years;
- In total, 363 of the 1045 (34%) evaluable patients experienced disease-free survival (DFS) events
- 257 patients died from any cause (221 with cancer recurrence)4
- No difference was noted in adjusted DFS, recurrence-free survival (RFS) or overall survival (OS) for past smokers compared with never smokers
The study was able to evaluate the impact of smoking on colon cancer recurrence and survival. Smoking status and smoking cessation did not appear to have a statistically significant impact on the primary endpoints of the study, including DFS or the secondary endpoints of OS or RFS. However, a dose-response association was found for smoking intensity, specifically for the risk of death or recurrence in higher numbers of pack-years smoked before age 30 in comparison to the nonsmokers.4
The authors point that this trial uniquely evaluates the risk of colon cancer recurrence in a cohort of patients with stage III colon cancer. Limitations to the study include that analyses are based on self-reporting of tobacco use and smoking history, however previous studies have shown a similar distribution of smoking status and past smoking intensity in other clinical trials in noncancer populations.4 They conclude that a dose-response for lifetime total of tobacco usage is present and may affect survival outcomes in patients with stage III colon cancer, especially for longer induction periods of usage prior to 30 years of age. The authors also note that more research is needed to determine the role of molecular markers and smoking history.
References
- Baris D, Karagas MR, Verrill C, et al. A case-control study of smoking and bladder cancer risk: emergent patterns over time. J Natl Cancer Inst. 2009;101 (22):1553-61.
- Chao A, Thun MJ, Jacobs EJ, et al. Cigarette smoking and colorectal cancer mortality in the Cancer Prevention Study II. J Natl Cancer Inst. 2000;92(23):1888-1896; doi:10.1093/jnci/92.93.1888. Free full text available at the following link: http://jnci.oxfordjournals.org/cgi/content/full/92/23/1888.
- Luchtenborg M, White KKL, Wilkens L, et al. Smoking and colorectal cancer: Different effects by type of cigarettes? Cancer Epidemiololog Biomarkers Prev. 2007;16(7):1341-1347; doi:10.1158/1055-9965.EPI-06-0519. Free full text available at the following link: http://cebp.aacrjournals.org/content/16/7/1341.full.pdf+html.
- McCleary NJ, Niedzwiecki D, Hollis D, et al. Impact of smoking on patients with stage III colon cancer. Cancer. 2010 Jan 5 [epub ahead of print]. doi: 10.1002/cncr.24866.