Home - News ( United States | United Kingdom | Italy | Germany ) - Football scores

Showing content from https://pmc.ncbi.nlm.nih.gov/articles/PMC6528653/ below:

Fruit and Vegetable Intakes and Risk of Colorectal Cancer and Incident and Recurrent Adenomas in the PLCO Cancer Screening Trial

. Author manuscript; available in PMC: 2019 May 21.

Int J Cancer. 2015 Dec 8;138(8):1851–1861. doi:

The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio _{3rd tertile vs. 1st tertile} = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) _{3rd tertile vs. 1st tertile} = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR= 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.

Keywords: Fruits, Vegetables, Colorectal cancer, Colorectal adenoma, Diet

Fruits and vegetables are an important, natural source of a variety of vitamins, fiber and antioxidants, which have been hypothesised to reduce risk of colorectal cancer ¹. However, despite a number of prospective investigations ^2–12, a consensus as to whether fruit and vegetables play an active protective role against colorectal cancer has not been made. A pooled analysis of 14 cohort studies reported that fruit and vegetable intake was not strongly associated with colon cancer overall, but may be associated with distal colon cancer ¹³. A 2011 update of the World Cancer Research Fund/American Institute for Cancer Research colorectal cancer report suggested there is only ‘limited suggestive evidence’ for a protective role of fruit and vegetable intakes against colorectal cancer ¹⁴.

There is particular uncertainty over the stages along the adenoma-carcinoma pathway, if any, at which fruit and vegetables act. A previous publication from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial identified that individuals with the highest quartile of fruit and vegetable intake had a 25% reduced risk of prevalent adenomas ¹⁵; however, other studies of adenoma have yielded mixed results ^9,16–23. Few studies of adenoma have been conducted prospectively ^17,18, making recall bias a possibility, and most have had limited ability to address the potential for detection or screening bias ¹⁷. Individuals with high fruit and vegetables intakes may be more likely to engage in other healthy behaviours including attending colorectal screening, which could lead to earlier detection of adenoma ²⁴ and a lower incidence of cancer.

We sought to further examine the temporal association between fruit and vegetable intake and the risk of incident and recurrent colorectal adenoma, and incident colorectal cancer in the intervention arm of a large prospective screening trial. Unlike many previous observational studies where opportunities for screening may be variable and thus prone to potential screening bias, in the screening arm of this trial individuals had equitable opportunities for colorectal screening and neoplasm detection.

Study participants were identified from the intervention arm of the PLCO Cancer Screening Trial, described previously ²⁵. Briefly, 154,952 individuals were recruited via ten centres in the USA (Birmingham, Alabama; Boulder, Colorado; Detroit, Michigan; Hawaii; Los Angeles, California; Minneapolis, Minnesota; Pittsburgh, Pennsylvania; Salt Lake City, Utah; St Louis, Missouri; Wisconsin; Washington, DC) between 1993 and 2001. Individuals were eligible for randomization if they were aged 55–74 years, had no history of prostate, lung, colorectal or ovarian cancer, were not undergoing cancer treatment, were not currently participating in another cancer screening or prevention trial, had not taken Finasteride in the previous six months. From 1995 onwards, individuals were not recruited if they had undergone a colonoscopy, sigmoidoscopy, barium enema or multiple prostate specific antigen tests in the previous three years. Participants were given a baseline risk factor questionnaire, which collected information on personal and family medical history, tobacco smoking habits, medication use, and anthropometry, and a food frequency questionnaire (FFQ). All participants provided written informed consent and the study was approved by the Institutional Review Boards at the National Cancer Institute and the ten recruitment centers.

A total of 77,445 participants were randomized to the screening arm of the trial. Individuals randomized to the intervention arm of the PLCO trial underwent a flexible sigmoidoscopy at baseline and at one follow-up visit, either three (T3) or five (T5) years after baseline. Individuals with abnormalities detected at screening were referred for follow-up to their usual health-care providers. Medical records from follow-up investigations were reviewed by trained personnel for relevant outcomes. Additional colorectal cancer diagnoses were ascertained through annual questionnaires and linkage to the National Death Index, confirmed via medical record review. This study was limited to individuals randomized to the intervention arm, who completed a baseline questionnaire and had no personal history of cancer (excluding non-melanoma skin cancer) (n=72,139). Additional exclusions and analytic criteria for each of the three outcomes evaluated are described below.

For analysis of incident colorectal cancer, individuals who did not complete the Food Frequency Questionnaire (FFQ) or had an inadequate FFQ [defined as ≥8 FFQ items missing or reported extreme energy intakes (< 1^st percentile or >99^th percentile of intake] were excluded (n=13,495). Individuals with a history of ulcerative colitis, Crohn’s disease, polyposis or Gardner’s disease, or with cancer diagnosis prior to completion of the FFQ were also excluded from analysis (n=869). Individuals were followed up from the time of FFQ completion to the date of colorectal cancer diagnosis, death, loss to follow-up, 13 years of follow-up or 31^st December 2009, whichever came first. After exclusions, 57,774 individuals remained for analysis, of whom 733 developed colorectal cancer over a median 12.1 years of follow-up.

For this analysis, only individuals who received an adequate sigmoidoscopy (defined as insertion ≥50cm with ≥90% of mucosa visible) at baseline that did not detect polyps, abnormal or suspicious findings, received an adequate sigmoidoscopy at T3/T5, and had no personal history of colorectal cancer by T3/T5 were eligible for analysis (n=22,500). Persons without evidence of polyps on both the T0 and T3/T5 screening exams were considered controls, and persons with a histologically confirmed adenoma in the distal colon or rectum detected on the T3/T5 screen, but not T0, were considered to have incident adenoma. Persons were excluded if they failed to complete the FFQ or had an inadequate FFQ (n=2,729), had a personal history of ulcerative colitis, Crohn’s disease, polyposis or Gardner’s syndrome (n=211), colorectal polyps (n=1,000), cancer, excluding non-melanoma skin cancers (n=634) or developed cancer during the trial period (n=944). After exclusions, 16,980 individuals remained for analysis, of whom 1,004 had an incident adenoma detected at either T3 or T5.

A subset of individuals randomized to the screening arm of the trial (n=5,013) were enrolled in a secondary study of colonoscopy utilization and completed a telephone-administered questionnaire regarding all colonoscopies performed over the 10 year follow-up since the baseline sigmoidoscopy. Medical records were obtained for all endoscopy procedures and relevant medical diagnoses abstracted. The current analysis was restricted to individuals who had an adenoma diagnosed at baseline and a follow-up endoscopy within the 0.5–10 year period after baseline (n=1,905). Again, individuals who did not complete the FFQ or had an inadequate FFQ (n=147), who had a personal history of ulcerative colitis, Crohn’s disease, polyposis or Gardner’s syndrome (n=13), cancer, excluding non-melanoma skin cancers (n=76) or unknown case status (n=2) were excluded from analysis. After exclusions, 1,667 individuals for analysis, of whom 738 had a recurrent colorectal adenoma during the ten-year time period.

Dietary intake of fruits and vegetables was measured using a self-administered 137-item food frequency questionnaire (FFQ), which inquired about usual dietary intake over the preceding year. The FFQ was modelled on three validated FFQs including the National Cancer Institute’s Diet History Questionnaire, the Block FFQ, and the Willett FFQ ²⁶, but was not validated itself. Nutrient and food group values were estimated using the My Pyramid food group servings database from the U.S. Department of Agriculture ²⁷ (Supplementary table 1).

Fruit and vegetable intakes were adjusted for energy using the nutrient density method ²⁸. Energy-adjusted fruit and vegetable intakes was categorised into tertiles of intake per 1,000kcal/d, based upon the distribution of intake in the colorectal cancer cohort. Chi-squared tests (categorical variables) and ANOVA (continuous variables) were used to assess the association between baseline characteristics and outcomes. Cox proportional hazards models were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between fruit and vegetable intake and the risk of colorectal cancer. Odds ratios (OR) and 95% CIs for the association between fruit and vegetable intake and the risk of incident and recurrent adenoma were estimated using unconditional logistic regression.

Base models were developed for each outcome which included age, gender, ethnicity, study center, total energy intake (kcal/day), screening during the trial, and adenoma at baseline or follow-up screens (for colorectal cancer), trial year (T3 or T5) of screening (for incident adenoma), surveillance period and number of surveillance endoscopies (for recurrent adenoma), as covariates. To further control for possible confounders in the analysis, full models were developed for the assessment of the association between each of the main exposures (i.e., total fruit and vegetables, total fruit, total vegetables) and each outcome (i.e., incident adenoma, recurrent adenoma & colorectal cancer). For the full models, additional confounders were added to the base model if they led to ≥ 10% change in the beta coefficient for the main exposure ²⁹. Additional factors tested in the model included education, exercise, smoking status, family history of colorectal cancer, use of non-steroidal anti-inflammatory drugs (NSAIDs), menopausal hormone therapy use (HRT), body mass index (BMI), and intakes of calcium, red meat, processed meat and alcohol. Tests for trend were assessed by assigning each individual in a particular tertile of fiber intake the median value for that tertile, prior to inclusion in the statistical model. Additional analyses were conducted with energy-adjusted intakes of fruits and vegetables modelled continuously.

Stratified analyses were conducted by age, sex, and additional confounders included in the respective further adjustment models. Interactions were tested using likelihood ratio tests comparing the models with and without the cross-product term. Additional sensitivity analyses by neoplasm location and disease severity were conducted for each of the outcomes. A two-tailed P-value < 0.05 was considered significant and analyses were conducted using Stata/SE statistical software (version 11.0, College Station, TX, USA).

Among the 57,774 individuals in the cohort, the median dietary intake of fruit and vegetables was 373g/d. Median energy intake was 1912kcal/d. Individuals in the highest tertile of energy-adjusted fruit and vegetable intake were more likely to be older, female, have lower BMIs, be physically active, be a HRT user and be a college graduate; and less likely to be of non-Hispanic white ethnicity, current smokers, have regularly used NSAIDs, or have a previous adenoma detected. Individuals with higher fruit and vegetable intakes also had greater calcium intakes but lower alcohol, red and processed meat intakes (Table 1).

Baseline characteristics of participants randomized to the intervention arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial, and eligible for analysis, by tertiles of fruit and vegetable intake.

Within the incident colorectal adenoma subset, adenoma cases were more likely to be male, of Non-Hispanic white ethnicity, current smokers, and have higher intakes of total energy, alcohol, red meat and processed meat and a higher body mass index but less likely to have higher total calcium intakes than non-cases. Within the recurrent colorectal adenoma subset, adenoma cases were more likely to be younger, male, current smokers, have a family history of colorectal cancer and have higher intakes of alcohol, and processed meat but less likely to be Non-Hispanic white or have high total calcium intakes than non-cases (Table 2).

Baseline characteristics of cases and controls in the incident and recurrent adenoma studies.

In base models, an inverse dose-response association was evident between incident colorectal adenoma risk and increased total fruit and vegetable intake (OR _{T3 v T1} 0.81, 95% CI: 0.68, 0.96, P_trend <0.07) but this association disappeared after further adjustment (OR 1.00, 95% CI: 0.83, 1.20) (Table 3). However, increasing fruit and vegetable intake continued to be associated with a reduced risk of multiple adenomas even after further adjustment (OR _{T3 v T1} 0.61, 95% CI: 0.38, 1.00, P_trend =0.04) (Supplementary Table 2).

The association between fruit and vegetable intake and risk of incident adenoma in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Results for incident adenoma were similar when fruit and vegetable variables were analysed as continuous variables (data not shown).

No significant interactions were observed with gender, smoking, BMI, or processed meat intake (P_interaction > 0.05; Supplementary Tables 3 & 4).

Similar to incident adenoma, there were no significant associations between fruit and vegetable intake and recurrent adenoma risk with or without adjustment for potential confounders (OR _{total fruits and vegetables T3 v T1} 0.87, 95% CI: 0.64, 1.20, P _trend=0.40). Results for incident adenoma were similar when fruit and vegetable variables were analysed as continuous variables (data not shown). Stratified analyses by adenoma location (Table 4) and advanced adenoma status (data not shown) also yielded null results.

The association between fruit and vegetable intake and the risk of recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

In base models, a significantly reduced risk of colorectal cancer was observed for individuals with higher total fruit and vegetable intakes (HR _{T3 v T1}=0.77, 95% CI: 0.63, 0.94, P_trend = 0.01), which became attenuated after further adjustment (HR _{T3 v T1}=0.82, 95% CI: 0.67, 1.01, P_trend = 0.05) (Table 5). Results were similar were similar when fruit and vegetable variables were analysed as continuous variables (data not shown). No differences were observed by cancer location with all showing weak, non-significant associations. No significant differences were observed by stage (data not shown), age, or gender (Supplementary Table 5). Interestingly, although the p-value for interactions were not significant, the protective association for total fruit and vegetable intake appeared stronger among those with intakes of processed meats above the median (HR =0.74, 95% CI: 0.55, 0.99, P_trend=0.07) compared to those with intakes below median (HR=0.90, 95% CI: 0.66, 1.21; P_interaction=0.42) and for ever smokers (HR=0.74, 95% CI: 0.61–1.03, P_trend=0.07) compared to never smokers (HR=0.90, 95% CI: 0.64–1.25; P_interaction=0.15) (Supplementary Table 6).

The association between fruit and vegetable intake and risk of colorectal cancer in the Prostate, Lung, Colorectal And Ovarian (PLCO) Cancer Screening Trial.

When analysed by type of fruit or vegetable consumed, a reduction in incident adenoma risk was noted in the base model amongst the highest consumers of ‘other fruits’, which includes solid fruits not within the citrus, berry and melon category (HR=0.77, 95% CI: 0.65, 0.91) (Supplementary Table 7) and moderate consumers of orange vegetables (HR=0.84, 95% CI: 0.72, 0.99) (Supplementary Table 8); however, these associations disappeared after further adjustment for other covariates. An increased risk was observed amongst individuals with the highest intakes of ‘other vegetables’, which includes vegetables not within the dark-green, orange or starch vegetable categories. No significant associations were observed for any type of fruit or vegetable for recurrent adenoma. High intake of citrus fruits, melons and berries was associated with a reduced risk of colorectal cancer (HR=0.79, 95% CI: 0.65, 0.95, P_trend=0.01); however, the association was no longer statistically significant after full adjustment (HR=0.85, 95% CI: 0.70, 1.03, P_trend=0.09). There were no statistically significant associations between any types of fruit or vegetable and risk of colon or rectal cancer after adjustment (data not shown).

Overall, the results of this large prospective cohort of screened individuals suggest that fruit and vegetable intakes are not associated with risk of incident or recurrent adenoma; however, high fruit and vegetable intakes may be associated with a reduced risk of multiple adenomas and colorectal cancer.

Previous studies of fruits and vegetables and adenoma have yielded mixed results ^9,15–18. Of those studies that have examined the association prospectively ^17,18, only the Nurse’s Health study examined fruit and vegetable intake in relation to incident adenoma, where cases and controls were adenoma-free in a previous endoscopy, and this study did find an inverse association between high fruit intake and incident adenoma detection at a later screen ¹⁷. Unlike in our study, not all participants in the Nurses’ Health Study received endoscopy as part of routine screening and the likelihood of adenoma detection may have differed based on the reason for endoscopy. High fruit and vegetable consumers may seek screening more readily ²⁴, so may be more likely to attend without symptoms, whereas low fruit and vegetable consumers may wait until symptoms develop before attending screening. Therefore, the evidence regarding a role of fruits and vegetables in adenoma development is mixed and may require further study.

Despite the lack of association with adenoma overall, we did see a protective association for total fruit and vegetable intake and the risk of multiple adenomas. This finding should be viewed cautiously due to the number of sub-group comparisons. Nevertheless, the association suggests that if high fruit and vegetable intake is protective for colorectal cancer, it may offer protection by reducing the number of adenomas and therefore, the likelihood that any one polyp will progress to cancer.

The lack of an association between fruit and vegetable intakes and risk of adenoma recurrence is consistent with previous results from the Polyp Prevention Trial, which found that randomisation to receive intensive counselling promoting a diet high in fruits, vegetables and fiber but low in fat did not reduce risk of adenoma recurrence compared to maintaining their current diet (Relative Risk = 0.98, 95% CI: 0.88, 1.09) ³⁰. It should be noted, however, dietary interventions may be require a longer time interval in order for their effects to be seen.

The World Cancer Research Fund/American Institute of Cancer Research continuous update report ³¹ concluded that there was only ‘limited suggestive’ evidence regarding an association between fruit and vegetable intakes and colorectal cancer risk based on a lack of evidence indicating a linear association ³². Nevertheless, another systematic review conducted at a similar time did find a significant non-linear association between fruit and vegetable intakes and colorectal cancer risk ³³ and the magnitude of the association is in line with those of the current study. Therefore, the lack of statistical significance in the current study could be attributable to insufficient statistical power to detect a relatively modest association.

Despite the lack of significance overall, there was an association between total fruit and vegetable intakes and risk of colorectal cancer amongst individuals with higher processed meat intakes. Processed meat consumption is thought to increase risk of colorectal cancer via production of carcinogenic N-nitroso compounds upon consumption ^34,35. Whilst this sub-group analysis should be interpreted with caution, it is biologically plausible and consistent with interactions observed for other gastrointestinal cancers ³⁶. Experimental studies indicate that vitamin C and other polyphenols found in fruits and vegetables may inhibit nitrosamine formation ³⁷ and dietary fiber, also found in fruits and vegetables, may reduce colonic exposure to carcinogens through dilution or reduced transit time ³⁸. This novel finding therefore warrants further investigation.

In regards to individual types of fruits and vegetables, there were no associations with risk of colorectal, colon or rectal cancer after full adjustment, which is largely consistent with existing literature ^4,7,39. Only ‘other’ vegetables, i.e. not within the dark-green, orange or starch vegetable categories (Supplementary table 1), were associated with risk of incident or recurrent adenoma. It is difficult to speculate on a shared biological mechanism by which this heterogeneous vegetable group would impact on adenoma development, and improved classification would be required in future studies to explore this further.

Our study had a number of strengths and weaknesses. In addition to the minimisation of detection bias for the adenoma outcomes, the prospective study design prevents the possibility of recall bias. The study also had robust data on a variety of potential confounders including smoking, BMI, physical activity and other dietary factors, allowing for multivariate adjustment. The use of the same source population for all of the outcomes allowed for a comprehensive evaluation of associations across the adenoma-carcinoma development pathway without the heterogeneity of multiple base populations. However, as flexible sigmoidoscopy only assesses the distal (left-sided) colon and rectum, proximal adenoma could not be evaluated and the results for distal or rectal adenoma may not be generalizable to proximal adenoma. Dietary assessment is also complex and food frequency questionnaires are not an ideal measure of habitual dietary intakes, so intakes of fruits and vegetables may have been underestimated, due to problems with recall ⁴¹. Whilst the misreporting is likely non-differential between groups, the ability to detect associations may have been reduced.

In conclusion, this prospective study, where all individuals underwent the same colorectal screening protocol, did not find evidence that high fruit and vegetable intakes are associated with a reduced risk of colorectal adenoma. The role of fruits and vegetables in risk of colorectal cancer remains unclear but our results suggest they may neutralise the detrimental effects of high processed meat intakes on colorectal carcinogenesis. Further studies are needed to examine the interaction between fruits and vegetables and processed meats on colorectal neoplasm risk.

8

This novel study uses data from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial to investigate the association between fruit and vegetable intakes and risk of incident and recurrent adenoma and incident colorectal cancer. Uniquely, this allowed the examination of incident adenoma risk with minimal detection bias, as all individuals were screened for adenoma at baseline, and had equitable opportunities for colorectal screening and neoplasm detection at a later screen.

This work was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, United states Department of Health and Human Services.

HR

Hazard ratio

CI

Confidence interva

OR

Odds ratio

WCRF

World Cancer Research Fund

AICR

American Institute for Cancer Research

EPIC

European Prospective Investigation into Cancer and Nutrition

FFQ

Food frequency questionnaire

PLCO

Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial

BMI

Body mass index

NSAIDs

Non-steroidal anti-inflammatory drug

HRT

Hormone replacement therapy

T0

Baseline

T3

3 years after baseline

T5

5 years after baseline

The authors report no conflicts of interest.

The Prostate, Lung, Colorectal, Ovarian Cancer Screening trial was registered at https://clinicaltrials.gov as NCT01696981.

• 1.Kaur C, Kapoor HC. Antioxidants in fruits and vegetables - the millennium’s health. Int J Food Sci Technol 2008;36:703–25. [Google Scholar]
• 2.Van Duijnhoven FJB, Bueno-De-Mesquita HB, Ferrari P, Jenab M, Boshuizen HC, Ros MM, Casagrande C, Tjønneland A, Olsen A, Overvad K, Thorlacius-Ussing O, Clavel-Chapelon F, et al. Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2009;89:1441–52. [DOI] [PubMed] [Google Scholar]
• 3.Park Y, Subar AF, Kipnis V, Thompson FE, Mouw T, Hollenbeck A, Leitzmann MF, Schatzkin A. Fruit and vegetable intakes and risk of colorectal cancer in the NIH-AARP diet and health study. Am J Epidemiol 2007;166:170–80. [DOI] [PubMed] [Google Scholar]
• 4.Nomura AM, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Pike MC, Kolonel LN. Association of vegetable, fruit, and grain intakes with colorectal cancer: the Multiethnic Cohort Study. Am J Clin Nutr 2008;88:730–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 5.Voorrips LE. Vegetable and Fruit Consumption and Risks of Colon and Rectal Cancer in a Prospective Cohort Study The Netherlands Cohort Study on Diet and Cancer. Am J Epidemiol 2000;152:1081–92. [DOI] [PubMed] [Google Scholar]
• 6.Terry P, Giovannucci E, Michels KB, Bergkvist L, Hansen H, Holmberg L, Wolk A. Fruit, Vegetables, Dietary Fiber, and Risk of Colorectal Cancer. J Natl Cancer Inst 2001;93:525–33. [DOI] [PubMed] [Google Scholar]
• 7.Michels KB. Prospective Study of Fruit and Vegetable Consumption and Incidence of Colon and Rectal Cancers. J Natl Cancer Inst 2000;92:1740–52. [DOI] [PubMed] [Google Scholar]
• 8.George SM, Park Y, Leitzmann MF, Freedman ND, Dowling EC, Reedy J, Schatzkin A, Hollenbeck A, Subar AF. Fruit and vegetable intake and risk of cancer: a prospective cohort study. Am J Clin Nutr 2009;89:347–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 9.Wu H, Dai Q, Shrubsole MJ, Ness RM, Schlundt D, Smalley WE, Chen H, Li M, Shyr Y, Zheng W. Fruit and vegetable intakes are associated with lower risk of colorectal adenomas. J Nutr 2009;139:340–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 10.Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, Fruit, and Colon Cancer in the lowa Women’s Health Study. Am J Epidemiol 1994;139:1–15. [DOI] [PubMed] [Google Scholar]
• 11.Sato Y, Tsubono Y, Nakaya N, Ogawa K, Kurashima K, Kuriyama S, Hozawa A, Nishino Y, Shibuya D, Tsuji I. Fruit and vegetable consumption and risk of colorectal cancer in Japan: The Miyagi Cohort Study. Public Health Nutr 2007;8:309–14. [DOI] [PubMed] [Google Scholar]
• 12.Aoyama N, Kawado M, Yamada H, Hashimoto S, Suzuki K, Wakai K, Suzuki S, Watanabe Y, Tamakoshi A. Low intake of vegetables and fruits and risk of colorectal cancer: the Japan Collaborative Cohort Study. J Epidemiol 2014;24:353–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 13.Koushik A, Hunter DJ, Spiegelman D, Beeson WL, van den Brandt PA, Buring JE, Calle EE, Cho E, Fraser GE, Freudenheim JL, Fuchs CS, Giovannucci EL, et al. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. J Natl Cancer Inst 2007;99:1471–83. [DOI] [PubMed] [Google Scholar]
• 14.WCRF/AICR. Continuous Update Project. Colorectal Cancer 2011 Report Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer. London: 2011. [Google Scholar]
• 15.Millen AE, Subar AF, Graubard BI, Peters U, Hayes RB, Weissfeld JL, Yokochi LA, Ziegler RG, for the Prostate LC and O (PLCO) CSTPT. Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial. Am J Clin Nutr 2007;86:1754–64. [DOI] [PubMed] [Google Scholar]
• 16.Smith-Warner SA. Fruits, Vegetables, and Adenomatous Polyps : The Minnesota Cancer Prevention Research Unit Case-Control Study. Am J Epidemiol 2002;155:1104–13. [DOI] [PubMed] [Google Scholar]
• 17.Michels KB, Giovannucci E, Chan AT, Singhania R, Fuchs CS, Willett WC. Fruit and vegetable consumption and colorectal adenomas in the Nurses’ Health Study. Cancer Res 2006;66:3942–53. [DOI] [PubMed] [Google Scholar]
• 18.Platz E, Giovannucci E, Rimm E, Rockett H, Stampfer M, Colditz G, Willett W. Dietary fiber and distal colorectal adenoma in men. Cancer Epidemiol Biomarkers Prev 1997;6:661–70. [PubMed] [Google Scholar]
• 19.Witte JS, Longnecker MP, Bird CL, Lee ER, Frankl HD, Haile RW. Relation of Vegetable, Fruit, and Grain Consumption to Colorectal Adenomatous Polyps. Am J Epidemiol 1996;144:1015–25. [DOI] [PubMed] [Google Scholar]
• 20.Almendingen K, Hofstad B, Vatn MH. Dietary habits and growth and recurrence of colorectal adenomas: results from a three-year endoscopic follow-up study. Nutr Cancer 2004;49:131–8. [DOI] [PubMed] [Google Scholar]
• 21.Mathew A, Peters U, Chatterjee N, Kulldorff M, Sinha R. Fat, fiber, fruits, vegetables, and risk of colorectal adenomas. Int J Cancer 2004;108:287–92. [DOI] [PubMed] [Google Scholar]
• 22.Austin GL, Adair LS, Galanko JA, Martin CF, Satia JA, Sandler RS. A Diet High in Fruits and Low in Meats Reduces the Risk of Colorectal Adenomas. J Nutr 2007;137:999–1004. [DOI] [PubMed] [Google Scholar]
• 23.Lubin F, Rozen P, Arieli B, Farbstein M, Knaani Y, Bat L, Farbstein H. Nutritional and lifestyle habits and water-fiber interaction in colorectal adenoma etiology. Cancer Epidemiol Biomarkers Prev 1997;6:79–85. [PubMed] [Google Scholar]
• 24.Shapiro JA, Seeff L., Nadel M Colorectal cancer-screening tests and associated health behaviors. Am J Prev Med 2001;21:132–7. [DOI] [PubMed] [Google Scholar]
• 25.Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford DE, Fogel R, Gelmann EP, Gilbert F, Hasson MA, Hayes RB, Johnson CC, et al. Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials 2000;21:273S–309S. [DOI] [PubMed] [Google Scholar]
• 26.Subar AF, Thompson FE, Kipnis V, Midthune D, Hurwitz P, McNutt S, McIntosh A, Rosenfeld S. Comparative Validation of the Block, Willett, and National Cancer Institute Food Frequency Questionnaires : The Eating at America’s Table Study. Am J Epidemiol 2001;154:1089–99. [DOI] [PubMed] [Google Scholar]
• 27.Bowman SA, Friday JE, Moshfegh AJ. MyPyramid Equivalents Database, 2.0 for USDA Survey Foods, 2003–2004 : Documentation and User Guide. Baltimore: 2004. [Google Scholar]
• 28.Willett W, Howe G, Kushi L. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 1997;65:1220S–1228. [DOI] [PubMed] [Google Scholar]
• 29.Maldonado G, Greenland S. Simulation Study of Confounder-Selection Strategies. Am J Epidemiol 1993;138:923–36. [DOI] [PubMed] [Google Scholar]
• 30.Schatzkin A, Lanza E, Corle D. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N Engl J Med 2000;342:1149–55. [DOI] [PubMed] [Google Scholar]
• 31.Asano T, McLeod RS. Dietary fibre for the prevention of colorectal adenomas and carcinomas. Cochrane database Syst Rev 2002;CD003430. [DOI] [PubMed] [Google Scholar]
• 32.Norat T, Greenwood D, Touvier M. WCRF / AICR Systematic Literature Review Continuous Update Project Report The Associations between Food, Nutrition and Physical Activity and the Risk of Colorectal Cancer. London: 2010. [Google Scholar]
• 33.Aune D, Lau R, Chan DSM, Vieira R, Greenwood DC, Kampman E, Norat T. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology 2011;141:106–18. [DOI] [PubMed] [Google Scholar]
• 34.Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer 2006;119:2657–64. [DOI] [PubMed] [Google Scholar]
• 35.Chan DSM, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, Norat T. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS One 2011;6:e20456. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 36.Jakszyn P, González C. Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence. World J Gastroenterol 2006;12:4296–303. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 37.Bartsch H, Ohshima H, Pignatelli B. Inhibitors of endogenous nitrosation mechanisms and implications in human cancer prevention. Mutat Res Mol Mech Mutagen 1988;202:307–24. [DOI] [PubMed] [Google Scholar]
• 38.Lupton JR, Turner ND. Potential protective mechanisms of wheat bran fiber. Am J Med 1999;106:24–7. [DOI] [PubMed] [Google Scholar]
• 39.Leenders M, Siersema PD, Overvad K, Tjønneland A, Olsen A, Boutron-Ruault M-C, Bastide N, Fagherazzi G, Katzke V, Kühn T, Boeing H, Aleksandrova K, et al. Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition. Int J cancer 2015; [DOI] [PubMed] [Google Scholar]
• 40.Wu QJ, Yang Y, Vogtmann E, Wang J, Han LH, Li HL, Xiang YB. Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies. Ann Oncol 2013;24:1079–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 41.Baldrick FR, Woodside JV, Elborn JS, Young IS, McKinley MC. Biomarkers of fruit and vegetable intake in human intervention studies: a systematic review. Crit Rev Food Sci Nutr 2011;51:795–815. [DOI] [PubMed] [Google Scholar]

This section collects any data citations, data availability statements, or supplementary materials included in this article.

8

RetroSearch is an open source project built by @garambo | Open a GitHub Issue

Search and Browse the WWW like it's 1997 | Search results from DuckDuckGo

HTML: 3.2 | Encoding: UTF-8 | Version: 0.7.3