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Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies.
Veettil, SK, Wong, TY, Loo, YS, Playdon, MC, Lai, NM, Giovannucci, EL, Chaiyakunapruk, N
JAMA network open. 2021;(2):e2037341
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IMPORTANCE Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate. OBJECTIVE To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC. DATA SOURCES MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019. EVIDENCE REVIEW Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses. CONCLUSIONS AND RELEVANCE This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
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The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.
Nguyen, LH, Cao, Y, Hur, J, Mehta, RS, Sikavi, DR, Wang, Y, Ma, W, Wu, K, Song, M, Giovannucci, EL, et al
Gastroenterology. 2021;(5):1423-1432.e4
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BACKGROUND & AIMS Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
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Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance).
Morales-Oyarvide, V, Yuan, C, Babic, A, Zhang, S, Niedzwiecki, D, Brand-Miller, JC, Sampson-Kent, L, Ye, X, Li, Y, Saltz, LB, et al
Journal of the National Cancer Institute. 2019;(2):170-179
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BACKGROUND Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. METHODS We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.
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An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States.
Tabung, FK, Giovannucci, EL, Giulianini, F, Liang, L, Chandler, PD, Balasubramanian, R, Manson, JE, Cespedes Feliciano, EM, Hayden, KM, Van Horn, L, et al
The Journal of nutrition. 2018;(5):771-780
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BACKGROUND The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. OBJECTIVE We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population. METHODS In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women's Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories. RESULTS Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend < 0.0001); IL-6, +15% (P-trend < 0.0001); TNF-α, +7% (P-trend = 0.0007); TNFR1, +4% (P-trend = 0.0009); TNFR2, +5% (P-trend < 0.0001); and adiponectin, -13% (P-trend <0.0001). These associations differed by racial/ethnic groups and by BMI categories. Whereas the absolute biomarker concentrations were lower among European-American women and among normal-weight women, the associations with diet were stronger than among women of African-American or Hispanic/Latino origin and among overweight and obese women. CONCLUSIONS Findings demonstrate the successful replication of an empirical hypothesis-oriented a posteriori dietary pattern score in a multi-ethnic population of postmenopausal women, with subgroup differences by race/ethnicity and body weight. Future research needs to apply the score in non-US populations.
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Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time.
Bernstein, AM, Song, M, Zhang, X, Pan, A, Wang, M, Fuchs, CS, Le, N, Chan, AT, Willett, WC, Ogino, S, et al
PloS one. 2015;(8):e0135959
Abstract
Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.