Originally published as JCO Early Release 10.1200/JCO.2006.06.0855 on July 5 2006

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyerhardt, J. A. Articles by Fuchs, C. S. Search for Related Content PubMed PubMed Citation Articles by Meyerhardt, J. A. Articles by Fuchs, C. S. Related Articles Related Editorial Social Bookmarking                            What's this?

Physical Activity and Survival After Colorectal Cancer Diagnosis

Jeffrey A. Meyerhardt, Edward L. Giovannucci, Michelle D. Holmes, Andrew T. Chan, Jennifer A. Chan, Graham A. Colditz, Charles S. Fuchs

From the Division of Medical Oncology, Dana-Farber Cancer Institute; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Harvard School of Public Health; Department of Medicine, Massachusetts General Hospital, Boston, MA

Address reprint requests to Jeffrey A. Meyerhardt, MD, MPH, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: jmeyerhardt{at}partners.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
PURPOSE: Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown.

PATIENTS AND METHODS: By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer–specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis. To minimize bias by occult recurrences, we excluded women who died within 6 months of their postdiagnosis physical activity assessment.

RESULTS: Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and overall mortality (P for trend = .003). Compared with women who engaged in less than 3 metabolic equivalent task [MET] -hours per week of physical activity, those engaging in at least 18 MET-hours per week had an adjusted hazard ratio for colorectal cancer–specific mortality of 0.39 (95% CI, 0.18 to 0.82) and an adjusted hazard ratio for overall mortality of 0.43 (95% CI, 0.25 to 0.74). These results remained unchanged even after excluding women who died within 12 and 24 months of activity assessment. Prediagnosis physical activity was not predictive of mortality. Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared with those with no change in activity.

CONCLUSION: Recreational physical activity after the diagnosis of stages I to III colorectal cancer may reduce the risk of colorectal cancer–specific and overall mortality.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
In both prospective^1-11 and retrospective^12-20 studies, physical activity is associated with a significant likelihood of developing colorectal cancer. The International Agency for Research on Cancer concluded that the evidence supports a causal relation between inactivity and colorectal cancer risk.²¹ However, it is largely unknown whether exercise influences survival of patients with established cancer.^22,23

Cancer patients often inquire about the utility of lifestyle changes beyond standard therapies.²⁴ Recent data suggest that physically active breast cancer survivors experience a superior survival compared with those who are more sedentary.²⁵ In a recent study of stage III colon cancer patients participating in an adjuvant chemotherapy trial, increasing postdiagnosis physical activity was associated with significant reductions in cancer recurrence and mortality.²² In the latter study, because data on activity before diagnosis were not available, the relative influence of prediagnosis and postdiagnosis exercise or change in activity could not be assessed.

We studied the impact of recreational physical activity among women with local and regional colorectal cancer who were participating in a large, prospective cohort study that was initiated before cancer diagnosis (the Nurses' Health Study).

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
Study Population
In 1976, the Nurses' Health Study (NHS) cohort was established when 121,700 female registered nurses answered a mailed questionnaire on risk factors for cancer and cardiovascular disease.^26,27 Every 2 years, participants receive follow-up questionnaires to update information on potential risk factors and report new cancer and disease diagnoses. This study was approved by the Human Subjects Committee at Brigham and Women's Hospital.

Measurement of Colon Cancer
On each biennial follow-up questionnaire, participants were asked whether they had had a diagnosis of colorectal cancer during the prior 2 years. When a participant (or next of kin for decedents) reported colorectal cancer, we sought permission to obtain records and pathology reports. Study physicians, blinded to exposure data, reviewed all records related to colorectal cancer and recorded stage, histology, and tumor location. For nonresponders, we searched the National Death Index to discover deaths and ascertain any diagnosis of colorectal cancer that contributed to death or was a secondary diagnosis. We estimate that 96% of the cases of colorectal cancer were identified through these various methods.²⁸ The individuals in this analysis were NHS participants with stage I to III colorectal cancer diagnosed between 1986 (when physical activity was first assessed) and 2002.

Measurement of Mortality
Women were observed until death or June 2004, whichever came first. Ascertainment of deaths included reporting by the family or postal authorities. In addition, the names of persistent nonresponders were searched in the National Death Index.²⁹ The cause of death was assigned by physicians blinded to exposures. In the case of a woman who died as a result of colorectal cancer not previously reported, we obtained medical records of the colorectal cancer diagnosis after permission from next of kin. More than 98% of deaths in the NHS have been identified by these methods.³⁰

Exclusions
Women were excluded if they presented with metastatic colorectal cancer at time of initial diagnosis or were diagnosed with any other cancer (other than nonmelanoma skin cancer) within 3 years of their colorectal cancer. Moreover, to minimize bias by occult recurrence or other undiagnosed major illnesses, we excluded women who died within 6 months of their postdiagnosis physical activity assessment. There were 573 women eligible for analysis.

Exposure Assessment
We assessed leisure-time physical activity in metabolic equivalent task (MET) -hours per week beginning in 1986, as briefly described.^2,25 Participants reported duration of participation (range, 0 to 11 or more hours per week) in walking (along with usual pace), jogging, running, bicycling, swimming laps, racket sports, other aerobic exercises, lower intensity exercise (yoga, toning, stretching), or other vigorous activities.

Although we only included women with stage I to III cancer, we presumed that those who eventually died as a result of colorectal cancer had metastatic disease before death. To avoid bias due to declining activity immediately before and after diagnosis of metastatic cancer, physical activity was not updated (thereby a single prediagnosis and single postdiagnosis measurement was determined).

Each activity on the questionnaire was assigned a MET score.³¹ One MET is the energy expenditure for sitting quietly. MET scores are defined as the ratio of the metabolic rate associated with specific activities divided by the resting metabolic rate. The values from the individual activities were summed for a total MET-hours per week score. Categories of MET-hours per week were predefined as less than 3, 3 to 8.9, 9 to 17.9, 18 or more, to correspond to the equivalent of less than 1, 1 to less than 3, 3 to less than 6, 6 or more hours per week of walking at an average pace, consistent with prior analyses.³² Our activity questionnaire has been validated previously against activity diaries.^33,34

For analyses of prediagnosis physical activity, the response from the immediate prior survey was used (median, 6 months before diagnosis). If a response were missing, one previous assessment would be carried forward; otherwise, the patient was not included in those analyses. For postdiagnosis analyses, the first physical activity assessment collected at least 1 year but no more than 4 years after diagnosis (median, 22 months) was used to avoid assessment during the period of active treatment. For change in activity, patients who changed from a higher to lower category before and after diagnosis, respectively, were categorized as decreasing activity, patients who changed from a lower to higher category were categorized as increasing activity, and patients who remained in the same category were categorized as no change.

Covariates
Stage of disease, grade of tumor differentiation, year of diagnosis, and location of tumor were extracted from the medical record. Beginning in 1993, women were asked methods of treatment in a supplemental questionnaire. The time interval between cancer diagnosis and assessment of activity was also adjusted for in these analyses. Body mass index (BMI) and smoking status (current, past, or never) were also taken from the biennial questionnaire at the time of the respective physical activity assessment.

Statistical Analyses
Cox proportional hazards models were used to calculate hazard ratios (HRs) of death or death as a result of colorectal cancer, adjusted for other risk factors for cancer survival. In the main analysis, death as a result of colorectal cancer was the primary end point and deaths as a result of other causes were censored. In secondary analyses, death as a result of any cause was the end point. The primary exposure of interest was physical activity after the diagnosis of colorectal cancer. In addition, we examined prediagnosis activity and change in physical activity. For the analyses of postdiagnosis physical activity and change in activity, participants were observed from the date of return of postdiagnosis physical activity assessment to either death or June 2004. In the analyses of physical activity before diagnosis, participants were observed from the date of diagnosis of colorectal cancer to either death or June 2004. The two-tailed P value for the linear trend test across categories was calculated by using the median value of each category as a continuous variable, consistent with prior studies.^2,25 Tests of interactions between physical activity categories and potential effect modifiers were assessed by entering in the model the cross product of the median of each physical activity category with the dichotomized covariate. All analyses used SAS version 8.0 (SAS Institute Inc, Cary, NC).

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
Baseline Characteristics by Physical Activity Category
Among the 573 eligible participants with stage I, II, or III colorectal cancer, there were 132 deaths, of which 80 were classified as colorectal cancer–specific deaths. The median time of follow-up from date of diagnosis of women who are alive was 9.6 years (with 95% observed for 5 or more years). Baseline characteristics of the 573 patients are shown according to categories of both prediagnosis and postdiagnosis physical activity (Table 1). In general, women who were more active had a lower BMI and were less likely to have smoked cigarettes.

For the analysis of 5-year survival, activity levels were collapsed into three categories (< 3, 3 to 17.9, and 18 MET-hours per week) based on the results described above (Figs 1 and 2). Of note, follow-up in this analysis begins at the time of completion of the questionnaire that assessed physical activity to reduce bias rather than the date of diagnosis of colorectal cancer, as is typically derived for studies for adjuvant chemotherapy. Nonetheless, the proportion of patients with colorectal cancer–specific deaths at 5 years (Fig 1) was 14.1% for patients who engaged in less than 3 MET-hours per week, 14.4% for patients who engaged in 3 to 17.9 MET-hours per week, and 6.2% for patients who engaged in 18 or more MET-hours per week (P log-rank = .004). There was also a statistically significant difference in overall survival across physical activity tertile (P = .02, Fig 2).

View larger version (14K): [in this window] [in a new window]   Fig 1. Cumulative incidence curve of colorectal cancer–specific deaths by level of postdiagnosis physical activity. MET, metabolic equivalent task.

View larger version (14K): [in this window] [in a new window]   Fig 2. Kaplan and Meier curve of overall survival by level of postdiagnosis physical activity. MET, metabolic equivalent task.

View larger version (11K): [in this window] [in a new window]   Fig 3. Impact of change of physical activity before and after colorectal cancer diagnosis. *Compared with no change. Adjusted for body mass index, stage of disease (I, II, III), grade of tumor differentiation, colon or rectal primary, age at diagnosis, year of diagnosis, receipt of chemotherapy (yes, no, unknown), time from diagnosis to physical activity measurement, change in body mass index, smoking status (current, past, never).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

Physical activity has been shown consistently to reduce colon cancer incidence.^1-20 Although the mechanism is unclear, the association with sedentary lifestyle and hyperinsulinemia is a potential etiology.^35-37 Insulin and the insulinlike growth factor family have been associated with enhanced tumor growth and antiapoptosis,³⁵ and colon cancer risk is elevated in individuals with higher circulating levels of insulin or C-peptide (a marker of insulin secretion) and insulinlike growth factor-1.^38-43 Colon cancer recurrences are believed to be growth of micrometastases. Thus, an environment that allows such microscopic tumors to proliferate could be detrimental. Whether insulinlike factors or other mechanisms potentially linked to physical activity would affect this environment is unknown.

In a separate cohort of men and women with stage III colon cancer, we reported a similar reduction in disease-free survival among patients physically active after diagnosis.²² The NHS provide provides several complementary advantages. First, given that patients who are more physical active after cancer diagnosis may have been active before diagnosis, we considered the possibility that physically active individuals who do develop colon cancer simply acquire tumors that are biologically less aggressive. However, physical activity levels before diagnosis were not predictive of cancer survival. Second, the NHS cohort provided a unique opportunity to explore the relationship of change in activity before and after diagnosis. It should be noted that greater than 50% of women changed levels of physical activity appreciably after diagnosis. Although a decrease in activity was not significantly associated with survival, increases in activity did seem to confer a significantly improved survival. The magnitude of benefit of increasing activity seemed similar in women who were both relatively inactive and more active before diagnosis. These analyses also demonstrate that women who were at a relatively higher level of activity before diagnosis should at least maintain such activity, but do not necessarily need to increase beyond that level. Nonetheless, because we do not know the reasons why these women increased their activity levels, these findings need to be confirmed.

Beyond cause of mortality, data on cancer recurrences were not available in this cohort. Nonetheless, given that median survival for metastatic colorectal cancer was approximately 10 to 12 months during much of the time period of this study,⁴⁴ colorectal cancer–specific mortality should be a reasonable surrogate for cancer-specific outcomes. Our cohort was restricted to women; it is possible that these findings might not apply to male patients with colorectal cancer. However, we did not observe a sex interaction in our prior study of postdiagnosis activity.²²

In this cohort, data on the treatment are limited. Two thirds of the women had stage I or II disease, in which surgery alone generally would be standard of care. Furthermore, although there are differences in the likelihood of use of adjuvant chemotherapy based on factors such as socioeconomic class, the fairly homogenous nature of this cohort (professional nurses) would likely increase the probability of at least standard therapy.^45,46 Moreover, as shown in Table 1, chemotherapy use (based on the available data) did not differ according to postdiagnosis physical activity levels. Comorbidities and access to health care may also confound these findings. Given the population studied (professional nurses), we would expect the latter to be relatively diminished. Although comorbidities have been shown to affect mortality in colorectal cancer survivors,^47-49 such diseases are less likely to affect disease recurrence and thereby colorectal cancer–specific mortality.

We cannot completely exclude the possibility that lower levels of physical activity may be reflective of other occult predictors for poor prognosis. However, we did not observe any significant associations between physical activity and other predictors of cancer outcome. Our findings remained unchanged after adjusting for potential risk factors for colorectal cancer mortality. Moreover, we found a consistent benefit for physical activity among patients with either stage I/II or stage III disease. Furthermore, we considered the possibility that sick patients (with cancer recurrences and limited survival) will exercise less. To minimize the bias by occult cancer recurrence, we excluded recurrences or deaths within 6 months of the activity assessment in the primary analysis and continued to observe a positive impact of exercise even when extending this restriction to 12 and 24 months. Finally, we would expect few patients to have undetected recurrences over extended periods of time, given the relatively brief natural history of recurrent colon cancer.

Patients who underwent treatment for colorectal cancer may be considered limited in their ability to exercise. However, Arndt et al⁵⁰ reported that 1 year after surgery of the primary tumor, patients with colorectal cancer reported their physical functioning and global quality of life nearly identical to those of a noncancer population. Furthermore, the distribution of levels of exercise in our study does not vary significantly by stage and is similar to that in other reports from the NHS in women without cancer.²

Our results suggest that physical activity after a colorectal cancer diagnosis may lower the risk of death from that disease. This benefit was seen regardless of age, BMI, stage, or site of disease. Along with our prior findings,²² these data suggest that, in addition to surgery and chemotherapy, increasing physical activity may confer additional benefit to patients with colorectal cancer.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
The authors indicated no potential conflicts of interest.

	Author Contributions

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 

Conception and design: Jeffrey A. Meyerhardt, Edward L. Giovannucci, Michelle D. Holmes, Charles S. Fuchs Financial support: Jeffrey A. Meyerhardt, Edward L. Giovannucci, Graham A. Colditz, Charles S. Fuchs Administrative support: Jeffrey A. Meyerhardt Provision of study materials or patients: Edward L. Giovannucci, Graham A. Colditz Collection and assembly of data: Edward L. Giovannucci, Graham A. Colditz, Charles S. Fuchs Data analysis and interpretation: Jeffrey A. Meyerhardt, Michelle D. Holmes, Andrew T. Chan, Jennifer A. Chan, Graham A. Colditz, Charles S. Fuchs Manuscript writing: Jeffrey A. Meyerhardt, Charles S. Fuchs Final approval of manuscript: Jeffrey A. Meyerhardt, Edward L. Giovannucci, Michelle D. Holmes, Andrew T. Chan, Jennifer A. Chan, Graham A. Colditz, Charles S. Fuchs

 

	NOTES

 
Supported in part by a K07 award from the National Cancer Institute (Grant No. K07CA097992-01A1) and an American Society of Clinical Oncology Career Development Award (J.A.M.). The Nurses' Health Study is supported in part by Grant No. P01CA087969 from the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
1. Lee IM, Paffenbarger RS Jr, Hsieh C: Physical activity and risk of developing colorectal cancer among college alumni. J Natl Cancer Inst 83:1324-1329, 1991[Abstract/Free Full Text]

2. Martinez ME, Giovannucci E, Spiegelman D, et al: Leisure-time physical activity, body size, and colon cancer in women: Nurses' Health Study Research Group. J Natl Cancer Inst 89:948-955, 1997[Abstract/Free Full Text]

3. Gerhardsson M, Floderus B, Norell SE: Physical activity and colon cancer risk. Int J Epidemiol 17:743-746, 1988[Abstract/Free Full Text]

4. Wu AH, Paganini-Hill A, Ross RK, et al: Alcohol, physical activity and other risk factors for colorectal cancer: A prospective study. Br J Cancer 55:687-694, 1987[Medline]

5. Thun MJ, Calle EE, Namboodiri MM, et al: Risk factors for fatal colon cancer in a large prospective study. J Natl Cancer Inst 84:1491-1500, 1992[Abstract/Free Full Text]

6. Ballard-Barbash R, Schatzkin A, Albanes D, et al: Physical activity and risk of large bowel cancer in the Framingham Study. Cancer Res 50:3610-3613, 1990[Abstract/Free Full Text]

7. Albanes D, Blair A, Taylor PR: Physical activity and risk of cancer in the NHANES I population. Am J Public Health 79:744-750, 1989[Abstract/Free Full Text]

8. Severson RK, Nomura AM, Grove JS, et al: A prospective analysis of physical activity and cancer. Am J Epidemiol 130:522-529, 1989[Abstract/Free Full Text]

9. Lynge E, Thygesen L: Use of surveillance systems for occupational cancer: Data from the Danish National system. Int J Epidemiol 17:493-500, 1988[Abstract/Free Full Text]

10. Paffenbarger RS Jr, Hyde RT, Wing AL: Physical activity and incidence of cancer in diverse populations: A preliminary report. Am J Clin Nutr 45:312-317, 1987[Free Full Text]

11. Giovannucci E, Ascherio A, Rimm EB, et al: Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med 122:327-334, 1995[Abstract/Free Full Text]

12. Fraser G, Pearce N: Occupational physical activity and risk of cancer of the colon and rectum in New Zealand males. Cancer Causes Control 4:45-50, 1993[CrossRef][Medline]

13. Longnecker MP, Gerhardsson le Verdier M, Frumkin H, et al: A case-control study of physical activity in relation to risk of cancer of the right colon and rectum in men. Int J Epidemiol 24:42-50, 1995[Abstract/Free Full Text]

14. Whittemore AS, Wu-Williams AH, Lee M, et al: Diet, physical activity, and colorectal cancer among Chinese in North America and China. J Natl Cancer Inst 82:915-926, 1990[Abstract/Free Full Text]

15. Kune GA, Kune S, Watson LF: Body weight and physical activity as predictors of colorectal cancer risk. Nutr Cancer 13:9-17, 1990[Medline]

16. Markowitz S, Morabia A, Garibaldi K, et al: Effect of occupational and recreational activity on the risk of colorectal cancer among males: A case-control study. Int J Epidemiol 21:1057-1062, 1992[Abstract/Free Full Text]

17. Peters RK, Garabrant DH, Yu MC, et al: A case-control study of occupational and dietary factors in colorectal cancer in young men by subsite. Cancer Res 49:5459-5468, 1989[Abstract/Free Full Text]

18. Brownson RC, Zahm SH, Chang JC, et al: Occupational risk of colon cancer: An analysis by anatomic subsite. Am J Epidemiol 130:675-687, 1989[Abstract/Free Full Text]

19. Kato I, Tominaga S, Matsuura A, et al: A comparative case-control study of colorectal cancer and adenoma. Jpn J Cancer Res 81:1101-1108, 1990[CrossRef]

20. Fredriksson M, Bengtsson NO, Hardell L, et al: Colon cancer, physical activity, and occupational exposures: A case-control study. Cancer 63:1838-1842, 1989[Medline]

21. Vainio H, Kaaks R, Bianchini F: Weight control and physical activity in cancer prevention: International evaluation of the evidence. Eur J Cancer Prev 11:S94-S100, 2002 (suppl 2)

22. Meyerhardt JA, Heseltine D, Niedzwiecki D, et al: Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. J Clin Oncol 24:3535-3541, 2006[Abstract/Free Full Text]

23. Haydon AM, Macinnis R, English D, et al: The effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut 55:62-67, 2006[Abstract/Free Full Text]

24. Brown JK, Byers T, Doyle C, et al: Nutrition and physical activity during and after cancer treatment: An American Cancer Society guide for informed choices. CA Cancer J Clin 53:268-291, 2003[Abstract/Free Full Text]

25. Holmes MD, Chen WY, Feskanich D, et al: Physical activity and survival after breast cancer diagnosis. JAMA 293:2479-2486, 2005[Abstract/Free Full Text]

26. Belanger CF, Hennekens CH, Rosner B, et al: The nurses' health study. Am J Nurs 78:1039-1040, 1978[Medline]

27. Colditz GA, Manson JE, Hankinson SE: The Nurses' Health Study: 20-year contribution to the understanding of health among women. J Womens Health 6:49-62, 1997[Medline]

28. Giovannucci E, Colditz GA, Stampfer MJ, et al: A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women. J Natl Cancer Inst 86:192-199, 1994[Abstract/Free Full Text]

29. Sathiakumar N, Delzell E, Abdalla O: Using the National Death Index to obtain underlying cause of death codes. J Occup Environ Med 40:808-813, 1998[CrossRef][Medline]

30. Stampfer MJ, Willett WC, Speizer FE, et al: Test of the National Death Index. Am J Epidemiol 119:837-839, 1984[Free Full Text]

31. Ainsworth BE, Haskell WL, Leon AS, et al: Compendium of physical activities: Classification of energy costs of human physical activities. Med Sci Sports Exerc 25:71-80, 1993

32. Colditz GA, Feskanich D, Chen WY, et al: Physical activity and risk of breast cancer in premenopausal women. Br J Cancer 89:847-851, 2003[CrossRef][Medline]

33. Wolf AM, Hunter DJ, Colditz GA, et al: Reproducibility and validity of a self-administered physical activity questionnaire. Int J Epidemiol 23:991-999, 1994[Abstract/Free Full Text]

34. Chasan-Taber S, Rimm EB, Stampfer MJ, et al: Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals. Epidemiology 7:81-86, 1996[Medline]

35. Sandhu MS, Dunger DB, Giovannucci EL: Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972-980, 2002[Abstract/Free Full Text]

36. Kaaks R, Lukanova A: Energy balance and cancer: The role of insulin and insulin-like growth factor-I. Proc Nutr Soc 60:91-106, 2001[Medline]

37. Giovannucci E: Insulin, insulin-like growth factors and colon cancer: A review of the evidence. J Nutr 131:3109S-3120S, 2001[Abstract/Free Full Text]

38. Schoen RE, Tangen CM, Kuller LH, et al: Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 91:1147-1154, 1999[Abstract/Free Full Text]

39. Kaaks R, Toniolo P, Akhmedkhanov A, et al: Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592-1600, 2000[Abstract/Free Full Text]

40. Palmqvist R, Stattin P, Rinaldi S, et al: Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: A prospective study in northern Sweden. Int J Cancer 107:89-93, 2003[CrossRef][Medline]

41. Palmqvist R, Hallmans G, Rinaldi S, et al: Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: A prospective study in northern Sweden. Gut 50:642-646, 2002[Abstract/Free Full Text]

42. Ma J, Pollak MN, Giovannucci E, et al: Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91:620-625, 1999[Abstract/Free Full Text]

43. Manousos O, Souglakos J, Bosetti C, et al: IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 83:15-17, 1999[CrossRef][Medline]

44. Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med 352:476-487, 2005[Free Full Text]

45. VanEenwyk J, Campo JS, Ossiander EM: Socioeconomic and demographic disparities in treatment for carcinomas of the colon and rectum. Cancer 95:39-46, 2002[CrossRef][Medline]

46. Schrag D, Cramer LD, Bach PB, et al: Influence of hospital procedure volume on outcomes following surgery for colon cancer. JAMA 284:3028-3035, 2000[Abstract/Free Full Text]

47. Payne JE, Meyer HJ: The influence of other diseases upon the outcome of colorectal cancer patients. Aust N Z J Surg 65:398-402, 1995[Medline]

48. Yancik R, Wesley MN, Ries LA, et al: Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: A population-based study. Cancer 82:2123-2134, 1998[CrossRef][Medline]

49. Piccirillo JF, Tierney RM, Costas I, et al: Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 291:2441-2447, 2004[Abstract/Free Full Text]

50. Arndt V, Merx H, Stegmaier C, et al: Quality of life in patients with colorectal cancer 1 year after diagnosis compared with the general population: A population-based study. J Clin Oncol 22:4829-4836, 2004[Abstract/Free Full Text]

Submitted February 8, 2006; accepted March 23, 2006.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Cancer Survival: Time to Get Moving? Data Accumulate Suggesting a Link Between Physical Activity and Cancer Survival
  Wendy Demark-Wahnefried
  JCO 2006 24: 3517-3518 [Full Text]

This article has been cited by other articles:

				J. A. Meyerhardt, S. Ogino, G. J. Kirkner, A. T. Chan, B. Wolpin, K. Ng, K. Nosho, K. Shima, E. L. Giovannucci, M. Loda, et al. Interaction of Molecular Markers and Physical Activity on Mortality in Patients with Colon Cancer Clin. Cancer Res., September 15, 2009; 15(18): 5931 - 5936. [Abstract] [Full Text] [PDF]

				C. Rabin Promoting Lifestyle Change Among Cancer Survivors: When Is the Teachable Moment? American Journal of Lifestyle Medicine, September 1, 2009; 3(5): 369 - 378. [Abstract] [PDF]

				R. F. Zoeller Jr Lifestyle in the Prevention and Management of Cancer: Physical Activity American Journal of Lifestyle Medicine, September 1, 2009; 3(5): 353 - 361. [Abstract] [PDF]

				A. T. Chan, S. Ogino, and C. S. Fuchs Aspirin Use and Survival After Diagnosis of Colorectal Cancer JAMA, August 12, 2009; 302(6): 649 - 658. [Abstract] [Full Text] [PDF]

				A. I. Neugut Aspirin as Adjuvant Therapy for Colorectal Cancer: A Promising New Twist for an Old Drug JAMA, August 12, 2009; 302(6): 688 - 689. [Full Text] [PDF]

				S. A. Duffy, D. L. Ronis, S. McLean, K. E. Fowler, S. B. Gruber, G. T. Wolf, and J. E. Terrell Pretreatment Health Behaviors Predict Survival Among Patients With Head and Neck Squamous Cell Carcinoma J. Clin. Oncol., April 20, 2009; 27(12): 1969 - 1975. [Abstract] [Full Text] [PDF]

				S. Ogino, K. Nosho, G. J. Kirkner, K. Shima, N. Irahara, S. Kure, A. T. Chan, J. A. Engelman, P. Kraft, L. C. Cantley, et al. PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer J. Clin. Oncol., March 20, 2009; 27(9): 1477 - 1484. [Abstract] [Full Text] [PDF]

				K. M. Bellizzi, J. H. Rowland, N. K. Arora, A. S. Hamilton, M. F. Miller, and N. M. Aziz Physical Activity and Quality of Life in Adult Survivors of Non-Hodgkin's Lymphoma J. Clin. Oncol., February 20, 2009; 27(6): 960 - 966. [Abstract] [Full Text] [PDF]

				B. M. Wolpin, J. A. Meyerhardt, A. T. Chan, K. Ng, J. A. Chan, K. Wu, M. N. Pollak, E. L. Giovannucci, and C. S. Fuchs Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer J. Clin. Oncol., January 10, 2009; 27(2): 176 - 185. [Abstract] [Full Text] [PDF]

				S. Ogino, K. Nosho, G. J Kirkner, T. Kawasaki, J. A Meyerhardt, M. Loda, E. L Giovannucci, and C. S Fuchs CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer Gut, January 1, 2009; 58(1): 90 - 96. [Abstract] [Full Text] [PDF]

				M L Irwin Physical activity interventions for cancer survivors Br. J. Sports Med., January 1, 2009; 43(1): 32 - 38. [Abstract] [Full Text] [PDF]

				J. A. Ligibel, W. Demark-Wahnefried, and P. J. Goodwin Diet, Exercise, and Supplements: Guidelines for Cancer Survivors ASCO Educational Book, January 1, 2009; 2009(1): 541 - 547. [Abstract] [Full Text] [PDF]

				S. Ogino, K. Nosho, J. A. Meyerhardt, G. J. Kirkner, A. T. Chan, T. Kawasaki, E. L. Giovannucci, M. Loda, and C. S. Fuchs Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer J. Clin. Oncol., December 10, 2008; 26(35): 5713 - 5720. [Abstract] [Full Text] [PDF]

				C. E. Mosher, I. M. Lipkus, R. Sloane, W. E. Kraus, D. C. Snyder, B. Peterson, L. W. Jones, and W. Demark-Wahnefried Cancer Survivors' Health Worries and Associations with Lifestyle Practices J Health Psychol, November 1, 2008; 13(8): 1105 - 1112. [Abstract] [PDF]

				J. A. Meyerhardt, D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, H. Nelson, R. Whittom, A. Hantel, J. Thomas, and C. S. Fuchs Impact of Body Mass Index and Weight Change After Treatment on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From Cancer and Leukemia Group B 89803 J. Clin. Oncol., September 1, 2008; 26(25): 4109 - 4115. [Abstract] [Full Text] [PDF]

				M. L. Irwin, A. W. Smith, A. McTiernan, R. Ballard-Barbash, K. Cronin, F. D. Gilliland, R. N. Baumgartner, K. B. Baumgartner, and L. Bernstein Influence of Pre- and Postdiagnosis Physical Activity on Mortality in Breast Cancer Survivors: The Health, Eating, Activity, and Lifestyle Study J. Clin. Oncol., August 20, 2008; 26(24): 3958 - 3964. [Abstract] [Full Text] [PDF]

				K. Ng, J. A. Meyerhardt, K. Wu, D. Feskanich, B. W. Hollis, E. L. Giovannucci, and C. S. Fuchs Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer J. Clin. Oncol., June 20, 2008; 26(18): 2984 - 2991. [Abstract] [Full Text] [PDF]

				C. M. Blanchard, K. S. Courneya, and K. Stein Cancer Survivors' Adherence to Lifestyle Behavior Recommendations and Associations With Health-Related Quality of Life: Results From the American Cancer Society's SCS-II J. Clin. Oncol., May 1, 2008; 26(13): 2198 - 2204. [Abstract] [Full Text] [PDF]

				K. S Courneya Physical Activity in Cancer Survivors: Possible Associations with Clinical Outcomes Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 417 - 420. [Abstract] [Full Text] [PDF]

				T. I.L. Nilsen, P. R. Romundstad, H. Petersen, D. Gunnell, and L. J. Vatten Recreational Physical Activity and Cancer Risk in Subsites of the Colon (the Nord-Trondelag Health Study) Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 183 - 188. [Abstract] [Full Text] [PDF]

				C. G. Willett, B. G. Czito, and J. C. Bendell Radiation Therapy in Stage II and III Rectal Cancer Clin. Cancer Res., November 15, 2007; 13(22): 6903s - 6908s. [Abstract] [Full Text] [PDF]

				J. A. Meyerhardt, D. Niedzwiecki, D. Hollis, L. B. Saltz, F. B. Hu, R. J. Mayer, H. Nelson, R. Whittom, A. Hantel, J. Thomas, et al. Association of Dietary Patterns With Cancer Recurrence and Survival in Patients With Stage III Colon Cancer JAMA, August 15, 2007; 298(7): 754 - 764. [Abstract] [Full Text] [PDF]

				B. K. Pedersen State of the Art Reviews: Health Benefits Related to Exercise in Patients With Chronic Low-Grade Systemic Inflammation American Journal of Lifestyle Medicine, August 1, 2007; 1(4): 289 - 298. [Abstract] [PDF]

				W. Demark-Wahnefried, E. C. Clipp, I. M. Lipkus, D. Lobach, D. C. Snyder, R. Sloane, B. Peterson, J. M. Macri, C. L. Rock, C. M. McBride, et al. Main Outcomes of the FRESH START Trial: A Sequentially Tailored, Diet and Exercise Mailed Print Intervention Among Breast and Prostate Cancer Survivors J. Clin. Oncol., July 1, 2007; 25(19): 2709 - 2718. [Abstract] [Full Text] [PDF]

				S. Ogino, T. Kawasaki, G. J. Kirkner, P. Kraft, M. Loda, and C. S. Fuchs Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample J. Mol. Diagn., July 1, 2007; 9(3): 305 - 314. [Abstract] [Full Text] [PDF]

				J. A. Chan, J. A. Meyerhardt, A. T. Chan, E. L. Giovannucci, G. A. Colditz, and C. S. Fuchs Hormone Replacement Therapy and Survival After Colorectal Cancer Diagnosis J. Clin. Oncol., December 20, 2006; 24(36): 5680 - 5686. [Abstract] [Full Text] [PDF]

				C. Doyle, L. H. Kushi, T. Byers, K. S. Courneya, W. Demark-Wahnefried, B. Grant, A. McTiernan, C. L. Rock, C. Thompson, T. Gansler, et al. Nutrition and Physical Activity During and After Cancer Treatment: An American Cancer Society Guide for Informed Choices CA Cancer J Clin, November 1, 2006; 56(6): 323 - 353. [Abstract] [Full Text] [PDF]

				J. A. Meyerhardt, D. Heseltine, D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, J. Thomas, H. Nelson, R. Whittom, A. Hantel, et al. Impact of Physical Activity on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 J. Clin. Oncol., August 1, 2006; 24(22): 3535 - 3541. [Abstract] [Full Text] [PDF]

				W. Demark-Wahnefried Cancer Survival: Time to Get Moving? Data Accumulate Suggesting a Link Between Physical Activity and Cancer Survival J. Clin. Oncol., August 1, 2006; 24(22): 3517 - 3518. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyerhardt, J. A. Articles by Fuchs, C. S. Search for Related Content PubMed PubMed Citation Articles by Meyerhardt, J. A. Articles by Fuchs, C. S. Related Articles Related Editorial Social Bookmarking                            What's this?