The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. In a prospective cohort study (Nurses’ Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991–2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all P_trend ≤ .03), driven by those identified in the distal colon and rectum (all P_trend ≤ .04, except AMED: P_trend = .14). Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

Diet quality scores (DQSs) are frequently used to study diet–disease relations but the validity of these scores derived from FFQs has rarely been evaluated. To evaluate the validity and reproducibility of 6 commonly used DQSs derived from the FFQ, including the Alternate Healthy Eating Index–2010, Dietary Approaches to Stop Hypertension Trial score, alternative Mediterranean diet score, and 3 plant-based diet indices (overall, healthful, and unhealthful). This analysis included 1394 participants from the Men's Lifestyle Validation Study (N = 652) and the Women's Lifestyle Validation Study (N = 742). Participants completed a 152-item FFQ at the beginning of the study and 1 y later, as well as completed 2 weighed 7-d dietary records (7DDRs) and donated 2 blood samples 6 mo apart between FFQ assessments. The reproducibility of the FFQs was evaluated by rank intraclass correlation coefficients (ICCs). The validity was assessed by comparing FFQ-derived DQSs with those from the average of two 7DDRs using Spearman rank correlation coefficients deattenuated for random measurement error in the 7DDRs (r_s). Furthermore, we calculated the correlations between DQSs and plasma biomarkers of diet, including fatty acids, folate, carotenoids, retinol, and α- and γ-tocopherol. Six FFQ-derived DQSs demonstrated moderate to high reproducibility (energy-adjusted ICCs: 0.61–0.84) and validity (energy-adjusted, deattenuated r_s = 0.56–0.80) in both men and women. We consistently observed expected correlations between FFQ-derived DQSs with plasma fatty acids, including long-chain n–3 (ω-3) and trans fatty acids, most carotenoids, and γ-tocopherol (r_s > 0.2). Our study demonstrates the validity of the FFQ to evaluate overall diet quality using 6 commonly used DQSs. In addition, these DQSs have qualitatively demonstrated biological relevance, as indicated by their correlations with circulating biomarkers.

Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. We followed 121,111 participants from 2 prospective US cohort studies, the Nurses’ Health Study (1984–2014) and Health Professionals Follow-Up Study (1986–2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (P_{heterogeneity} ≤ 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; P_trend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; P_trend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.

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.

Background: Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies. Methods and findings: Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America. A total of 2,494,432 participants without cancer at baseline (62% women, 84% European ancestries, 70% alcohol drinkers [alcohol intake ≥ 0.1 g/day], 47% never smokers) were recruited between 1980 and 2013 at the median age of 57 years and 10,067 incident pancreatic cancer cases were recorded. In age- and sex-stratified Cox proportional hazards models adjusted for smoking history, diabetes status, body mass index, height, education, race and ethnicity, and physical activity, pancreatic cancer hazard ratios (HR) and 95% confidence intervals (CI) were estimated for categories of alcohol intake and in continuous for a 10 g/day increase. Potential heterogeneity by sex, smoking status, geographic regions, and type of alcoholic beverage was investigated. Alcohol intake was positively associated with pancreatic cancer risk, with HR_{30-to-<60 g/day} and HR_≥60 g/day equal to 1.12 (95% CI [1.03,1.21]) and 1.32 (95% CI [1.18,1.47]), respectively, compared to intake of 0.1 to <5 g/day. A 10 g/day increment of alcohol intake was associated with a 3% increased pancreatic cancer risk overall (HR: 1.03; 95% CI [1.02,1.04]; p_value < 0.001) and among never smokers (HR: 1.03; 95% CI [1.01,1.06]; p_value = 0.006), with no evidence of heterogeneity by sex (p_{heterogeneity} = 0.274) or smoking status (p_{heterogeneity} = 0.624). Associations were consistent in Europe–Australia (HR_10 g/day = 1.03, 95% CI [1.00,1.05]; p_value = 0.042) and North America (HR_10 g/day = 1.03, 95% CI [1.02,1.05]; p_value < 0.001), while no association was observed in cohorts from Asia (HR_10 g/day = 1.00, 95% CI [0.96,1.03]; p_value = 0.800; p_{heterogeneity} = 0.003). Positive associations with pancreatic cancer risk were found for alcohol intake from beer (HR_10 g/day = 1.02, 95% CI [1.00,1.04]; p_value = 0.015) and spirits/liquor (HR_10 g/day = 1.04, 95% CI [1.03,1.06]; p_value < 0.001), but not wine (HR_10 g/day = 1.00, 95% CI [0.98,1.03]; p_value = 0.827). The differential associations across geographic regions and types of alcoholic beverages might reflect differences in drinking habits and deserve more investigations. Conclusions: Findings from this large-scale pooled analysis support a modest positive association between alcohol intake and pancreatic cancer risk, irrespective of sex and smoking status. Associations were particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.