Different operationalizations of the 2018 WCRF/AICR cancer prevention recommendations and risk of cancer.

BACKGROUND: The standardized scoring system assessing adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations assigns equal weight for each recommendation, thereby giving higher weight to dietary factors collectively (5 points) than adiposity (1 point) and physical activity (1 point). An alternative score assigning equal weights to the adiposity, physical activity, alcohol, and other dietary (composite) recommendations may better predict cancer associations. METHODS: We examined associations between standardized and alternative scores with cancer risk in two US prospective cohorts. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: During 28 years of follow-up, 16,342 incident cancer cases in women and 8729 cases in men occurred. Individuals in the highest versus lowest quintile of the standardized score had a reduced overall cancer risk (women: HR = 0.89, 95% CI: 0.85, 0.94; men: HR = 0.87, 95% CI: 0.81, 0.94). Results were slightly stronger for the alternative score (women: HR = 0.83, 95% CI: 0.79, 0.87; men: HR = 0.81, 95% CI: 0.75, 0.86). Similar patterns were observed for obesity-related, alcohol-related, smoking-related, and digestive system cancers. CONCLUSIONS: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with lower cancer risk. A score assigning equal weights to the adiposity, physical activity, alcohol, and all remaining diet components yielded stronger associations than the standardized score.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and Colorectal Cancer Survival.

BACKGROUND: Patients with cancer are recommended to follow cancer prevention guidelines due to inadequate evidence for specific recommendations for cancer survivors. METHODS: We examined whether diet and lifestyle scores measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention guidelines were associated with colorectal cancer-specific and overall mortality among 1,491 patients with colorectal cancer in two prospective cohorts. Cox proportional hazards regression models were used to calculate the multivariable-adjusted HRs and 95% confidence intervals (CI). RESULTS: During a median follow-up of 7.92 years, there were 641 deaths (179 colorectal cancer-specific deaths). Patients in the highest quartile of the post-diagnostic WCRF/AICR lifestyle score including diet, body mass index (BMI), and physical activity had a 24% lower risk (HR = 0.76, 95% CI: 0.49-1.18) of colorectal cancer-specific mortality and a 37% lower risk (HR = 0.63, 95% CI: 0.50-0.78) of overall mortality compared with the lowest quartile. When BMI was not included in the lifestyle score due to potential disease-related weight loss, stronger inverse associations were observed for both colorectal cancer-specific and overall mortality for the same comparison (colorectal cancer-specific: HR = 0.50, 95% CI: 0.32-0.79; overall: HR = 0.59, 95% CI: 0.47-0.75). The post-diagnostic WCRF/AICR diet score was not statistically significantly associated with either colorectal cancer-specific or overall mortality. CONCLUSIONS: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with improved survival in patients with colorectal cancer. IMPACT: This study provides support for patients with colorectal cancer to follow cancer prevention recommendations after diagnosis. Future studies on cancer survivors will continue to contribute to evidence-based diet and lifestyle recommendations for patients with cancer.

Dietary inflammatory potential, oxidative balance score, and risk of breast cancer: Findings from the Sister Study.

Diet, inflammation, and oxidative stress may be important in breast carcinogenesis, but evidence on the role of the inflammatory and prooxidative potential of dietary patterns is limited. Energy adjusted-Dietary Inflammatory Index (E-DII™) and dietary oxidative balance score (D-OBS) were calculated for 43 563 Sister Study cohort participants who completed a Block 1998 food frequency questionnaire at enrollment in 2003-2009 and satisfied eligibility criteria. D-OBS was validated using measured F2 -isoprostanes and metabolites. High E-DII score and low D-OBS represent a more proinflammatory and prooxidant diet, respectively, and associations of quartiles of each index with breast cancer (BC) risk were estimated using multivariable Cox proportional hazards regression. There were 2619 BCs diagnosed at least 1 year after enrollment (mean follow-up 8.4 years). There was no overall association between E-DII and BC risk, whereas there was a suggestive inverse association for the highest vs lowest quartile of D-OBS (HR 0.92 [95% CI, 0.81-1.03]). The highest quartile of E-DII was associated with risk of triple-negative BC (HR 1.53 [95% CI, 0.99-2.35]). When the two indices were combined, a proinflammatory/prooxidant diet (highest tertile of E-DII and lowest tertile of D-OBS) was associated with increased risk for all BC (HR 1.13 [95% CI, 1.00-1.27]) and for triple-negative BC (1.72 [95% CI, 1.10-2.70]), compared to an antiinflammatory/antioxidant diet (lowest tertile of E-DII and highest tertile of D-OBS). Diets with increased inflammatory potential and reduced oxidative balance were positively associated with overall and triple-negative BC.

Prenatal and childhood predictors of hair cortisol concentration in mid-childhood and early adolescence.

BACKGROUND: Hair cortisol concentration (HCC) is an increasingly used measure of systemic cortisol concentration. However, determinants of HCC in children and adolescents are unclear because few prospective studies have been conducted to date. STUDY DESIGN: We followed 725 children in Project Viva, a pre-birth cohort study of mothers and children, who provided hair samples at mid-childhood (median age: 7.7 years) or early adolescence (median age: 12.9 years). We examined associations of various factors measured from pregnancy to mid-childhood with HCC in mid-childhood and early adolescence, as well as change in HCC between these time points (ΔHCC). RESULTS: There were 426 children with HCC measurements in both mid-childhood and early adolescence, 173 children with measures only in mid-childhood, and 126 with measures only in early adolescence. HCC was lower in mid-childhood (median 1.0pg/mg [interquartile range, IQR: 0.5, 2.4]) than early adolescence (2.2pg/mg [1.1, 4.4]). In multivariable-adjusted regression models, female sex (ß = -0.41, 95% CI: -0.67, -0.15) and birth weight-for-gestational age z-score (ß = -0.19, 95% CI: -0.33, -0.04) were associated with lower mid-childhood HCC, while prenatal smoking was associated with higher mid-childhood HCC (ß = 0.53, 95% CI: 0.04, 1.01). In early adolescence, child age (ß = 0.34 per year, 95% CI: 0.21, 0.46) female sex (ß = 0.33, 95% CI: 0.10, 0.57), and maternal pre-pregnancy body mass index (ß = 0.15 per 5-kg/m2, 95% CI: 0.01, 0.29) were positively associated with HCC. Child anthropometric measures and biomarker concentrations were not associated with HCC. CONCLUSION: Maternal pre-pregnancy BMI, maternal prenatal smoking, and low birth weight were associated with higher mid-childhood and adolescent HCC. However, few postnatal characteristics were associated with HCC.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research 2018 Recommendations for Cancer Prevention and Risk of Colorectal Cancer.

BACKGROUND: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 2018 diet, nutrition, and physical activity recommendations aim to reduce cancer risk. We examined adherence to the WCRF/AICR recommendations and colorectal cancer risk in two prospective cohorts. METHODS: We followed 68,977 women in the Nurses' Health Study and 45,442 men in the Health Professionals Follow-up Study from 1986 until 2012. We created cumulatively averaged WCRF/AICR scores using updated diet, adiposity, and physical activity data from questionnaires, and used Cox regression to estimate sex-specific HRs and 95% confidence intervals (CI) for incident colorectal cancer. RESULTS: We documented 2,449 colorectal cancer cases. Men in the highest quintile of the WCRF/AICR lifestyle score had a lower risk of colorectal cancer compared with those in the lowest quintile (HRQ5vsQ1 = 0.64; 95% CI, 0.52-0.77). The result was weaker in women (HRQ5vsQ1 = 0.86; 95% CI, 0.72-1.02; P heterogeneity by sex = 0.006). When analyzing the diet recommendations alone, we similarly observed stronger inverse associations in men (HRQ5vsQ1 = 0.74; 95% CI, 0.61-0.90) compared with women (HRQ5vsQ1 = 0.93; 95% CI, 0.77-1.12; P heterogeneity by sex = 0.06). In men, the lifestyle score was more strongly inversely associated with risk of distal colon cancer compared with proximal colon or rectal cancer (P common effects = 0.03); we did not observe significant differences between anatomic locations in women. CONCLUSIONS: The 2018 WCRF/AICR cancer prevention recommendations are associated with lower colorectal cancer risk in men, with weaker results in women. IMPACT: Consideration of adiposity and physical activity in conjunction with diet is important for colorectal cancer prevention.

Dietary index scores and invasive breast cancer risk among women with a family history of breast cancer.

BACKGROUND: Many epidemiologic studies have analyzed the relations of individual foods and nutrients and breast cancer risk with inconsistent results. Few studies have examined recommendation-based dietary indices and breast cancer risk. OBJECTIVE: The aim of this study was to determine associations between recommendation-based dietary index scores and incident invasive breast cancer. METHODS: The Sister Study is a prospective cohort of 50,884 US women (baseline: 2003-2009) who had a sister with breast cancer but no prior breast cancer themselves. We created scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index-2010 (AHEI-2010) from dietary intakes estimated by a baseline-validated Block food-frequency questionnaire (FFQ). We used Cox regression to estimate multivariable-adjusted HRs and 95% CIs for total invasive breast cancer risk and by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status. RESULTS: We documented 1,700 invasive breast cancer cases through 2015 (mean follow-up, 7.6 y). Individuals in the highest quartile of DASH scores had a lower risk of invasive breast cancer compared with those in the lowest quartile (HR: 0.78; 95% CI: 0.67, 0.90; P-trend = 0.001), with stronger associations for ER- (HR: 0.61; 95% CI: 0.40, 0.94; P-trend = 0.006) as well as ER-/PR- and ER-/PR-/HER2- subtypes. AHEI-2010 (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.78, 1.03; P-trend = 0.15) and AMED (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.77, 1.06; P-trend = 0.07) were weakly and nonsignificantly associated with breast cancer risk, but after excluding alcohol, AHEI-2010 was inversely associated with risk of ER-/PR- (HR: 0.64; 95% CI: 0.42, 0.98; P-trend = 0.04) and ER-/PR-/HER2- subtypes. We did not observe any significant interactions by menopausal status or other participant characteristics. CONCLUSIONS: DASH scores were inversely associated with breast cancer risk; DASH and AHEI-2010 scores excluding alcohol were particularly inversely associated with risk of ER-/PR- and ER-/PR-/HER2- breast cancers. This trial was registered at clinicaltrials.gov as NCT00047970.

Mediation of associations between adiposity and colorectal cancer risk by inflammatory and metabolic biomarkers.

Inflammation and hyperinsulinemia may drive associations between adiposity and colorectal cancer (CRC) risk, but few studies have examined this hypothesis using mediation analysis. We used inverse odds ratio weighting and logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for estimated total effects (ORTE ) of body mass index, waist circumference, and adult weight gain on CRC risk, and estimated effects operating through seven inflammatory and metabolic biomarkers (natural indirect effect; ORNIE ) or through paths independent of these biomarkers (natural direct effect; ORNDE ) among 209 CRC cases and 382 matched controls nested within the Health Professionals Follow-up Study, a prospective cohort of male health professionals. A one-interquartile range (IQR) increase in body mass index (3.6 kg/m2 ) was associated with an ORTE of 1.40 (95% CI: 1.13, 1.73), which decomposed into an ORNIE of 1.26 (95% CI: 0.97, 1.52) and an ORNDE of 1.11 (0.87, 1.42), with possibly stronger mediation by these biomarkers for adult weight gain (IQR = 10.4 kg; ORTE = 1.32 [95% CI: 1.06, 1.64]; ORNIE = 1.47 [95% CI: 1.01, 1.81]; ORNDE = 0.89 [95% CI: 0.72, 1.11]), but no mediation for waist circumference. Mediation appeared to be stronger for the metabolic biomarkers than the inflammatory biomarkers. Inflammatory and metabolic mechanisms may mediate associations between both body mass index and adult weight gain with CRC risk.

Recommendation-based dietary indexes and risk of colorectal cancer in the Nurses' Health Study and Health Professionals Follow-up Study.

Background: Many dietary indexes exist for chronic disease prevention, but the optimal dietary pattern for colorectal cancer prevention is unknown. Objective: We sought to determine associations between adherence to various dietary indexes and incident colorectal cancer in 2 prospective cohort studies. Design: We followed 78,012 women in the Nurses' Health Study and 46,695 men in the Health Professionals Follow-up Study from 1986 and 1988, respectively, until 2012. We created dietary index scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index-2010 (AHEI-2010) and used Cox regression to estimate HRs and 95% CIs for risk of colorectal cancer (CRC) and by anatomic subsite. We also conducted latency analyses to examine associations between diet and CRC risk during different windows of exposure. We conducted analyses in men and women separately, and subsequently pooled these results in a random-effects meta-analysis. Results: We documented 2690 colorectal cancer cases. Pooled multivariable HRs for colorectal cancer risk comparing the highest to lowest quintile of diet scores were 0.89 (95% CI: 0.74, 1.08; P-trend = 0.10) for DASH, 0.89 (95% CI: 0.73, 1.10; P-trend = 0.31) for AMED, and 0.95 (95% CI: 0.83, 1.09; P-trend = 0.56) for AHEI-2010 (P-heterogeneity ≥ 0.07 for all). In sex-specific analyses, we observed stronger associations in men for all dietary indexes (DASH: multivariable HR = 0.81, 95% CI: 0.66, 0.98; P-trend = 0.003; AMED: multivariable HR = 0.80, 95% CI: 0.65, 0.98; P-trend = 0.02; AHEI-2010: multivariable HR = 0.88, 95% CI: 0.72, 1.07; P-trend = 0.04) than in women (multivariable HRs range from 0.98 to 1.01). Conclusions: Adherence to the DASH, AMED, and AHEI-2010 diets was inversely associated with colorectal cancer risk in men. These diets were not associated with colorectal cancer risk in women. This observational study was registered at http://www.clinicaltrials.gov as NCT03364582.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR.

Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer.

The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. PATIENT SUMMARY: We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.