Diet and Lifestyle in Survivors of Colorectal Cancer




Much research supports the association between diet and lifestyle in the development of colorectal cancer. Recent studies have demonstrated an association between various energy balance host factors (obesity, physical inactivity, and certain dietary factors) and outcomes. This review summarizes the impact of modifiable lifestyle factors, including prediagnosis and postdiagnosis adiposity, physical activity, and diet, on the prognosis of patients with colorectal cancer. The article focuses on associations of these factors in survivors of stage I to III colorectal cancer, and summarizes the possible mechanisms for the association between modifiable lifestyle factors and the prognosis of patients with colorectal cancer.


Key points







  • •

    Lifestyle factors that include obesity, physical activity, and diet are emerging as potential critical elements in improving survival outcomes for colorectal cancer.


  • •

    Changes in individual health behaviors both before and after a diagnosis of colorectal cancer may improve outcomes of survivors.


  • •

    Studies have indicated that maintaining a normal weight, participating in regular physical activity, and eating a healthy diet may be important preventive steps leading to improved survival outcomes.


  • •

    Epigenetic studies have demonstrated, at the cellular level, the possible mechanisms of colorectal cancer that can be positively influenced by changing lifestyle.




Introduction


The American Cancer Society estimates that there are more than 1.1 million survivors of colorectal cancer in the United States. Survivors of colorectal cancer constitute 10% of the total number of cancer survivors, and the number is increasing. Both genetic and lifestyle factors contribute to cancer development and the prognosis of colorectal cancer. Because lifestyle factors such as obesity, physical inactivity, diet, smoking, and alcohol consumption are potentially modifiable while genetic factors are not, much attention has been paid to the impact of lifestyle factors on the incidence and prognosis of colorectal cancer.


Changing these modifiable factors toward practice of a healthy lifestyle may be crucial components of cancer treatment in addition to standard treatments in preventing recurrence and improving survival of patients with colorectal cancer. Although an increasing number of studies have examined the association of diet and lifestyle factors with cancer recurrence and survival outcome in patients with locally advanced colorectal cancer, it is important to distinguish whether these exposures were measured before or after cancer diagnosis. For example, adiposity before diagnosis and after diagnosis may have a different impact on survival outcomes of patients with colorectal cancer. Exposures after diagnosis associated with prognosis of cancer may provide important implications on directing recommendations to cancer survivors. However, if an association exists only between prediagnosis adiposity and prognosis of colorectal cancer, it is less certain how to guide a patient, although such data may be important in understanding the biology of colorectal cancer.


This review summarizes the associations of modifiable lifestyle factors, including prediagnosis and postdiagnosis adiposity, physical activity, and diet, on the prognosis of patients with colorectal cancer. Given that most published data to date are from patients without metastatic disease, the focus here is on associations of these factors in survivors of stage I to III colorectal cancer. This article also summarizes the possible mechanisms for the association between modifiable lifestyle factors and the prognosis of patients with colorectal cancer.


Association between the prediagnosis lifestyle factors and risk of mortality in survivors of colorectal cancer


Adiposity


Several studies have examined the association between prediagnosis adiposity and the prognosis of colorectal cancer ( Table 1 ). These studies used a variety of metrics for adiposity, including body mass index (BMI; calculated as weight in kilograms divided by height in meters squared, ie, kg/m 2 ), waist-hip ratio (WHR), and waist circumference (WC). Campbell and colleagues examined 2303 men and women with stage I to III colorectal cancer and reported that those with BMI higher than 25 had worse colorectal cancer–specific mortality and all-cause mortality. Similarly, Doria-Rose and colleagues studied 633 postmenopausal women with colorectal cancer and reported that obese patients (BMI ≥30) had a 2.1-fold higher risk of colorectal cancer–specific mortality and all-cause mortality compared with patients of normal weight.



Table 1

Prospective cohort studies of prediagnosis body mass index (BMI, kg/m 2 ) and survival outcomes in patients with colorectal cancer
















































































































































































































































Authors, Ref. Year, Name of Cohort, Country Study Participants Median Years of Follow-Up Relative Risk/Hazard Ratio (95% Confidence Interval) Adjustment Factors
Doria-Rose, et al, 2006, Wisconsin Cancer Reporting System, USA 633 female
Colon and rectal 		9.4 CRC-specific mortality Age, stage, postmenopausal hormone use, and smoking
<20.0 1.6 (0.9–3.1)
20.0–24.9 Referent
25.0–29.9 1.3 (0.9–1.9)
≥30 1.5 (0.9–2.6)
All-cause mortality
<20.0 1.5 (1.0–2.4)
20.0–24.9 Referent
25.0–29.9 1.2 (0.9–1.6)
≥30 1.5 (1.0–2.2)
Prizment et al, 2010, Iowa Women’s Health Study, USA 1096 female
Colon 		20 CRC-specific mortality Stage, age, education, and smoking
<18.5 1.84 (0.84–4.03)
18.5.0–24.9 Referent
25.0–29.9 1.18 (0.87–1.52)
≥30 1.35 (1.00–1.82)
All-cause mortality
<18.5 1.89 (1.01–3.53)
18.5–24.9 Referent
25.0–29.9 1.12 (0.89–1.41)
≥30 1.45 (1.14–1.85)
Kuiper et al, 2012, Women’s Health Initiative, USA 1339 female
Colon and rectal 		11.9 CRC-specific mortality Age, study arm, BMI, tumor stage, ethnicity, education, alcohol, smoking, hormone therapy use
18.5–24.9 Referent
25.0–29.9 0.77 (0.52–1.13)
≥30 1.17 (0.80–1.72)
All-cause mortality
18.5–24.9 Referent
25.0–29.9 0.90 (0.66–1.23)
≥30 1.19 (0.88–1.62)
Campbell et al, 2012, Cancer Prevention Study-II Nutrition Cohort, USA 2303 both genders
Colon and rectal 		16 CRC-specific mortality Age, sex, smoking status, BMI, red meat intake, tumor stage, leisure time spent sitting, education
Female
<18.5 0.83 (0.25–2.76)
18.5.0–24.9 Referent
25.0–29.9 1.19 (0.80–1.78)
≥30 1.52 (0.96–2.41)
Male
<18.5 Not reported
18.5.0–24.9 Referent
25.0–29.9 1.06 (0.77–1.48)
≥30 1.31 (0.88–1.95)
Both
<18.5 0.67 (0.21–2.12)
18.5.0–24.9 Referent
25.0–29.9 1.09 (0.85–1.40)
≥30 1.35 (1.01–1.80)
All-cause mortality
Female
<18.5 1.74 (0.85–3.58)
18.5.0–24.9 Referent
25.0–29.9 1.22 (0.95–1.63)
≥30 1.42 (1.01–2.00)
Male
<18.5 1.40 (0.55–3.56)
18.5.0–24.9 Referent
25.0–29.9 0.97 (0.79–1.19)
≥30 1.21 (0.94–1.57)
Both
<18.5 1.53 (0.88–2.66)
18.5.0–24.9 Referent
25.0–29.9 1.06 (0.90–1.25)
≥30 1.30 (1.06–1.58)
Pelser et al, 2014, NIH-AARP Diet and Health Study, USA 4213 colon 1514 rectal
Both genders 		5 CRC-specific mortality among colon cancer cases Lag time, sex, education, family history of colon cancer, cancer stage, first course of treatment (surgery, radiation, chemotherapy), and also mutually adjusted for quintiles of HEI-2005 scores, BMI, physical activity, alcohol, and smoking history
18.5–24.9 Referent
25.0–29.9 0.97 (0.82–1.15)
≥30 1.15 (0.96–1.39)
All-cause mortality
18.5–24.9 Referent
25.0–29.9 1.02 (0.88–1.17)
≥30 1.19 (1.02–1.39)
CRC-specific mortality among rectal cancer cases
18.5–24.9 Referent
25.0–29.9 0.92 (0.70–1.22)
≥30 1.04 (0.75–1.44)
All-cause mortality
18.5–24.9 Referent
25.0–29.9 0.85 (0.68–1.07)
≥30 1.00 (0.77–1.30)


Other studies have reported similar findings when using alternative measurements for adiposity such as percent body fat, WC, and WHR. Haydon and colleagues reported that patients with colorectal cancer with increasing WC per 10 cm had a 1.33-times higher risk of disease-specific death. The investigators concluded that prediagnosis abdominal obesity might be a critical risk factor for mortality in patients with all-cause mortality, and made the recommendation for maintaining a normal weight and WC. In a study that compared BMI, weight, WHR, and WC, Prizment and colleagues reported that whereas higher BMI (≥25) and weight (≥63.5 kg) were not significantly associated with colon cancer mortality, higher WHR (≥0.81) and WC (≥82.5 cm) were significantly associated with mortality. This study suggested that WHR and WC, which reflect abdominal adiposity, might be better predictors of colon cancer mortality than BMI and weight.


Physical Activity


Reports on association between the level of physical activity before cancer diagnosis and the risk of mortality in patients with colorectal cancer have been mixed ( Table 2 ). Some studies found significant associations between level of prediagnosis physical activity levels and the risk of mortality, whereas others have found no association. Meyerhardt and colleagues studied female patients with stage I to III colorectal cancer and did not find any association between the level of prediagnosis physical activity and the risk of mortality. On the other hand, Haydon and colleagues found that prediagnosis physical activity level was significantly associated with increased disease-specific survival. The authors have recently performed a meta-analysis of the association between prediagnosis physical activity and the risk of mortality in patients with stage I to III colorectal cancer. The meta-analysis demonstrated that patients with colorectal cancer who participated in any amount of physical activity exhibited 25% and 24% risk reduction in colorectal cancer–specific death and death from all causes, respectively, compared with patients who did not participate in any physical activity. The study also found a dose-dependent risk reduction in colorectal cancer–specific death and all-cause death, suggesting that those who participated in more physical activity before diagnosis have a lower risk of recurrence and death after the completion of standard therapy.



Table 2

Prospective cohort studies of prediagnosis physical activity and survival outcomes in patients with colorectal cancer






























































































































































Authors, Ref. Year, Name of Cohort, Country Study Participants Median Years of Follow-Up Relative Risk/Hazard Ratio (95% Confidence Interval) Adjustment Factors
Haydon et al, 2006, Melbourne Collaborative Cohort Study, Australia 526 both genders
Colon and rectal 		5.5 CRC-specific mortality Age, sex, stage, BMI
Exerciser vs nonexerciser 0.73 (0.54–1.00)
All-cause mortality
Exerciser vs nonexerciser 0.77 (0.58–1.03)
Meyerhardt et al, 2006, Nurses’ Health Study, USA 573 female
Colon and rectal 		9.6 CRC-specific mortality Age, stage, tumor differentiation, year of diagnosis, time between study entry to questionnaire, BMI, smoking
<3 MET-h/wk Referent
3–8.9 0.83 (0.45–1.53)
9–17.9 1.05 (0.56–1.99)
≥18 0.86 (0.44–1.67)
All-cause mortality
<3 MET-h/wk Referent
9–8.9 0.85 (0.52–1.37)
9–17.9 1.14 (0.69–1.87)
≥18 0.95 (0.57–1.59)
Meyerhardt et al, 2009, Health Professionals Follow-up Study, USA 599 male
Colon and rectal 		8.6 CRC-specific mortality Age, stage, year of diagnosis, tumor differentiation, tumor location, BMI, smoking
<3 MET-h/wk Referent
3.1–9.0 0.56 (0.28–1.13)
9.1–18 0.64 (0.33–1.24)
18.1–27 0.53 (0.26–1.10)
≥27 0.52 (0.29–0.94)
All-cause mortality
<3 MET-h/wk Referent
3.1–9.0 0.55 (0.36–0.85)
9.1–18 0.60 (0.41–0.89)
18.1–27 0.51 (0.34–0.79)
≥27 0.48 (0.34–0.69)
Kuiper et al, 2012, Women’s Health Initiative, USA 1339 female
Colon and rectal 		11.9 CRC-specific mortality Age, study arm, BMI, tumor stage, ethnicity, education, alcohol, smoking, hormone therapy use
0 MET-h/wk Referent
>0–2.9 0.98 (0.58–1.66)
3.0–8.9 1.01 (0.65–1.57)
9.0–17.9 0.74 (0.46–1.20)
≥18.0 0.68 (0.41–1.13)
All-cause mortalit y
0 MET-h/wk Referent
>0–2.9 0.93 (0.61–1.43)
3.0–8.9 1.01 (0.71–1.43)
9.0–17.9 0.77 (0.52–1.12)
≥18.0 0.63 (0.42–0.96)
Campbell et al, 2013, Cancer Prevention Study-II, USA 2262 both genders
Colon and rectal 		6.8 CRC-specific mortality Age, sex, smoking status, BMI, red meat intake, tumor stage, leisure time spent sitting, education
<3.5 MET-h/wk Referent
3.5–<8.75 0.68 (0.49–0.95)
≥8.75 0.78 (0.57–1.08)
All-cause mortality
<3.5 MET-h/wk Referent
3.5–<8.75 0.69 (0.55–0.85)
≥8.75 0.72 (0.58–0.89)

Abbreviation: MET-h/wk, metabolic-equivalent task hours per week.


Diet


Diverse dietary factors are related to the development of colorectal cancer, yet few studies have focused on diet before diagnosis and mortality for patients with colorectal cancer ( Table 3 ). Among the diverse dietary factors, there is relatively consistent evidence that red and processed meat is related to an increased risk of colorectal cancer. Recently, McCullough and colleagues collected diet information from 2315 participants diagnosed with colorectal cancer in 1992/1993, 1999, and 2003, and followed their mortality through December 31, 2010. Those with higher red and processed meat intake (fourth quartile) before cancer diagnosis were reported to have a 29% and 63% increase in all-cause and cardiovascular disease mortality, respectively, compared with those with low red and processed meat intake (first quartile). An association between the amount of red and processed meat intake and colorectal cancer–specific mortality was not observed. Furthermore, Zell and colleagues studied 511 patients with colorectal cancer (144 familial and 376 sporadic colorectal cancer), and found that those who had high meat intake had reduced 10-year overall survival (4th quartile 42% vs 1st–3rd quartile 65%) and a 2.24-times increased risk of death in an adjusted analysis compared with those who had low meat intake among familial patients with colorectal cancer. No association was observed between the amount of meat intake and overall survival in sporadic patients with colorectal cancer. In addition, Zhu and colleagues performed a 1-year recall of meat intake in 529 survivors of colorectal cancer and reported that the highest quartile of processed meat intake was significantly associated with poorer disease-free survival (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.07–3.09) and overall survival (HR 2.13, 95% CI 1.03–4.43) in patients with colon cancer. However, they did not observe any significant association between the amount of processed meat intake and survivor outcomes in patients with rectal cancer. Furthermore, they found no associations between prudent vegetable or the high-sugar pattern and disease-free and overall survival in patients with colon and rectal cancer.



Table 3

Prospective cohort studies of prediagnosis diet and survival outcomes in patients with colorectal cancer









































Authors, Ref. Year, Name of Cohort, Country Study Participants Median Years of Follow-Up Dietary Measure Relative Risk/Hazard Ratio (95% Confidence Interval) Adjustment Factors
Zell et al, 2006, USA 511 both genders
Colon and rectal 		7.9 Red and processed meat All-cause mortality Age, stage, and sex
Quartiles 1–3 vs Quartiles 4 Familial CRC; 2.24 (1.25–4.03)
Sporadic CRC; 1.02 (0.67–1.15)
Zhu et al, 2013, Newfoundland Familial Colorectal Cancer Registry, Canada 529 both genders
Colon and rectal 		6.4 Processed meat dietary pattern Disease-free survival Total energy intake, sex, age at diagnosis, stage at diagnosis, marital status, family history, reported screening procedure, reported chemoradiotherapy and microsatellite instability status, where appropriate.
Highest vs lowest quartile 1.82 (1.07–3.09)
McCullough et al, 2013, Cancer Prevention Study-II Nutrition Cohort, USA 2315 both genders
Colon and rectal 		7.5 Red and processed meat All-cause mortality Age at diagnosis, sex, tumor stage at diagnosis, 1992 energy intake
Top vs bottom quartile 1.29 (1.05–1.59)

Abbreviation: CRC, colorectal cancer.


Mechanism for Prediagnosis Energy Balance Factors and Outcomes


Several hypotheses on why energy balance–associated host factors before diagnosis may negatively affect the prognosis of colorectal cancer have been proposed. First, many patients who have unfavorable energy balance (ie, obese or physically inactive) before diagnosis will be in a similar situation after diagnosis. Obesity and physical inactivity are associated with insulin resistance and subsequent hyperinsulinemia, which is linked to increased risk for cancer and mortality because it induces insulin-like growth factors (IGFs) that promote cancer growth. Patients with colorectal cancer with higher levels of C-peptide (a breakdown product of insulin production at the time of diagnosis) have shown higher mortality compared with those who had lower levels of C-peptide. Also, these host factors induce an increasing level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, or leptin that promotes cancer growth, along with a decreasing level of adiponectin that also promotes cancer growth. Given that the primary risk for patients with stage I to III colorectal cancer is growth of occult micrometastases, such growth factors can stimulate micrometastases that lead to recurrent disease.


Prediagnosis obesity or physical inactivity may affect the molecular nature of the colorectal cancer that develops, leading to more aggressive histology. For example, obesity and physical inactivity are associated with the development of CTNNB1 (β-catenin)-negative colorectal cancer. CTNNB1 tumors have a trend toward worse colorectal cancer–specific survival. In obese patients, nuclear CTNNB1 negativity was associated with significantly worse cancer-specific and overall survival. Similarly, among patients with nuclear CTNNB1-negative stage I to III, postdiagnosis physical activity was associated with significantly better cancer-specific survival, whereas physical activity was not associated with survival among patients with nuclear CTNNB1-positive stage I to III.


In terms of red and processed meat and survival, prior research has indicated that several factors may be instrumental in cancer development. Such factors include: (1) production of heterocyclic amines when meat is cooked at high temperature ; (2) involvement of N -nitroso compounds from the heme in the gastrointestinal tract ; and (3) use of nitrosamines, N -nitroso compounds, and their precursors, owing to nitrite or nitrate use in the preservation of meat. However, it is unclear if increased exposure to these factors will lead to more aggressive cancers.


Association between postdiagnosis lifestyle factors and the risk of mortality


Adiposity


Reports on postdiagnosis BMI and outcomes in colorectal cancer have been mixed ( Table 4 ). Some studies showed that being obese may have a negative impact on the survival of colorectal cancer, whereas other studies showed that there is no association between postdiagnosis obesity and the prognosis of colorectal cancer. In one early report, Meyerhardt and colleagues examined the association between obesity and prognosis of patients with stage II and III colon cancer, and found that female patients with a BMI of 30 or greater were associated with a 34% significant increase in mortality and a 24% nonstatistically significant increase in disease recurrence, whereas there was no such association between obesity and disease recurrence in men. Dignam and colleagues reported on a similar population of patients with colon cancer, and found a statistically significant 38% increase in the risk of recurrence and 28% increase in the risk of mortality among patients with a BMI greater than or equal to 35, and did not find an interaction by gender. One study, limited to patients with rectal cancer, did not show any significant association between BMI and disease-free or overall survival, although subgroup analyses by Campbell and colleagues did suggest that obesity was associated with worse outcomes in patients with rectal cancer.


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Mar 1, 2017 | Posted by in HEMATOLOGY | Comments Off on Diet and Lifestyle in Survivors of Colorectal Cancer

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