Self-Reported Eating-Occasion Frequency and Timing are Reproducible and Relatively Valid in the American Cancer Society Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Accurate assessment of eating-occasion behaviors, such as timing, frequency, and consumption intervals, is important for evaluating associations with obesity and other chronic diseases. OBJECTIVES: The main objective of this study was to assess the relative validity of a 24-hour grid approach to assess eating-occasion timing and frequency in comparison to data derived from repeated 24-hour dietary recalls (DRs). A second objective was to assess the 1-year test-retest reproducibility of the 24-hour grid. METHODS: Between 2015 and 2016, 626 participants in the Cancer Prevention Study-3 (CPS-3) Diet Assessment Substudy (mean age, 52 years; age range, 31-70 years; 64% female; 64% non-Hispanic white, 22% non-Hispanic black, 14% Hispanic) completed 2 grids and up to 6 unannounced, telephone, interviewer-administered DRs over 1 year. Spearman correlations (ρ; 95% CIs) were calculated to assess reproducibility between the repeated eating-occasion grid-derived variables (e.g., numbers of snacks and meals per day, timing of eating occasions) and to assess relative validity by comparing the meal grid and DR-derived summary data separately for weekdays and weekend days. RESULTS: Reproducibility correlations for eating-occasion variables derived from the eating-occasion grids completed 1 year apart were ≥0.5 for the majority of variables analyzed for both weekdays and weekend days, including numbers of snacks and meals per day and timing of the first and last eating occasions of the day. Relative validity was highest among weekday variables and was ≥0.5 for the majority of variables, with correlations ranging from ρ values of 0.32 (number of meals per day) to 0.68 (hour of the first eating occasion). CONCLUSIONS: These findings suggest the eating-occasion grid used in CPS-3 has good reproducibility over 1 year and yields estimates comparable to those from a more detailed method of assessment of eating timing and frequency.

Sugar- and Artificially-Sweetened Beverages and Cancer Mortality in a Large U.S. Prospective Cohort.

BACKGROUND: Sugar-sweetened beverage (SSB) consumption may be associated with cancer mortality independent of, or indirectly through, established influences on increased body adiposity. METHODS: We examined the associations of SSBs and artificially-sweetened beverages (ASB) with mortality from all-cancers combined, obesity-related cancers combined, and 20 cancer types, among men and women in the Cancer Prevention Study-II (CPS-II) prospective cohort. In 1982, 934,777 cancer-free participants provided information on usual SSB and ASB consumption. Deaths were identified through 2016. Multivariable Cox proportional hazards regression models examined associations of beverage types with cancer mortality, without and with BMI adjustment. RESULTS: During follow-up, 135,093 CPS-II participants died from cancer. Consumption of ≥2 SSB drinks/day vs. never was not associated with all-cancer mortality, but was associated with increased risk of obesity-related cancers [HR, 1.05; 95% confidence intervals (CI), 1.01-1.08; Ptrend = 0.057], which became null after adjustment for BMI. SSBs were associated with increased mortality from colorectal (HR, 1.09; 95% CI, 1.02-1.17; Ptrend = 0.011), and kidney (HR, 1.17; 95% CI, 1.03-1.34; Ptrend = 0.056) cancers, which remained after BMI adjustment. A positive association of ASB consumption with obesity-related cancers (HR, 1.05; 95% CI, 1.01-1.08; Ptrend = 0.001) was null after controlling for BMI; however, an increased risk of pancreatic cancer was robust to BMI adjustment (HR, 1.11; 95% CI, 1.02-1.20; Ptrend < 0.008). CONCLUSIONS: SSB consumption was associated with higher mortality from certain cancers, partially mediated through obesity. Associations of ASB consumption and increased pancreatic cancer risk merit further study. IMPACT: Future research should consider the role of BMI in studies of sweetened beverages and cancer risk. These results should inform policy regarding sweetened beverage consumption.

The Associations of Multivitamin and Antioxidant Use With Mortality Among Women and Men Diagnosed With Colorectal Cancer.

BACKGROUND: Colorectal cancer survivors often use multivitamins and other over-the-counter dietary supplements, but evidence is limited regarding their potential associations with mortality. METHODS: This prospective analysis included women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer-free at baseline (1992 or 1993) and diagnosed with colorectal cancer through June 2015. Detailed information on multivitamin use, vitamin C supplements, and vitamin E supplements was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 3176 and 2006 colorectal cancer survivors, respectively, among whom 2116 (648 from colorectal cancer) and 1256 (242 from colorectal cancer) died. Multivariable-adjusted Cox proportional hazards regression models examined associations. All statistical tests were 2-sided. RESULTS: Among colorectal cancer survivors, 49.7% and 58.5% reported multivitamin use before and after diagnosis, respectively (vitamin C use before and after diagnosis: 27.8% and 28.1%; vitamin E use before and after diagnosis: 27.5% and 29.4%, respectively). There were no statistically significant associations of pre- or postdiagnosis multivitamin use with all-cause, colorectal cancer-specific, or noncolorectal cancer mortality. Vitamin C was also not associated with any mortality outcomes. However, prediagnosis vitamin E use was associated with a non-statistically significant increased risk of all-cause mortality (multivariable adjusted hazard ratio = 1.08, 95% confidence intervals = 0.96 to 1.23) and all other noncolorectal cancer mortality (multivariable adjusted hazard ratio = 1.13, 95% confidence intervals = 0.97 to 1.31). CONCLUSIONS: These results suggest that multivitamin use before or after diagnosis is not associated with mortality in colorectal cancer survivors. However, vitamin E use may be associated with increased risk of mortality and merits further investigation.

Prospective associations of hemoglobin A1c and c-peptide with risk of diabetes-related cancers in the Cancer Prevention Study-II Nutrition Cohort.

Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A1c (HbA1c) and c-peptide with cancers associated with self-reported T2DM. This study was drawn from a prospective cohort of 32,383 women and men who provided blood specimens at baseline: c-peptide and HbA1c were assessed in 3,000 randomly selected participants who were cancer-free-at-baseline and an additional 2,281 participants who were cancer-free-at-baseline and subsequently diagnosed with incident colorectal, liver, pancreatic, female breast, endometrial, ovarian, bladder, or kidney cancers. Weighted-Cox regression models estimated hazards ratios (HRs) and 95% confidence intervals (CI), adjusted for covariates. C-peptide was associated with higher risk of liver cancer (per standard deviation (SD) HR: 1.80; 95%CI: 1.32-2.46). HbA1c was associated with higher risk of pancreatic cancer (per SD HR: 1.21 95%CI 1.05-1.40) and with some suggestion of higher risks for all-cancers-of-interest (per SD HR: 1.05; 95%CI: 0.99-1.11) and colorectal (per SD HR: 1.09; 95%CI: 0.98-1.20), ovarian (per SD HR: 1.18; 95%CI 0.96-1.45) and bladder (per SD HR: 1.08; 95%CI 0.96-1.21) cancers. Compared to no self-reported T2DM and HbA1c <6.5% (reference group), self-reported T2DM and HbA1c <6.5% (i.e., T2DM in good glycemic control) was not associated with risk of colorectal cancer, whereas it was associated with higher risks of all-cancers-of-interest combined (HR: 1.28; 95%CI: 1.01-1.62), especially for breast and endometrial cancers. Additional large, prospective studies are needed to further explore the roles of hyperglycemia, hyperinsulinemia, and related metabolic traits with T2DM-associated cancers to better understand the mechanisms underlying the self-reported T2DM-cancer association and to identify persons at higher cancer risk.

Associations of Aspirin and Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs With Colorectal Cancer Mortality After Diagnosis.

BACKGROUND: Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival. METHODS: This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 2686 and 1931 participants without distant metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between prediagnosis aspirin use and stage at diagnosis (distant metastatic vs localized or regional). All statistical tests were 2-sided. RESULTS: Long-term regular use of aspirin (>15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52 to 0.92). Postdiagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82, 95% CI = 0.62 to 1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre- and postdiagnosis periods (HR = 0.60, 95% CI = 0.36 to 0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73, 95% CI = 0.53 to 0.99). CONCLUSIONS: Our results suggest that long-term aspirin use before a diagnosis of nonmetastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micrometastases before diagnosis.

Composition of time in movement behaviors and weight change in Latinx, Black and white participants.

BACKGROUND: The relationship between time-use behaviors and prospective weight change is poorly understood. METHODS: A subset of Cancer Prevention Study-3 participants (n = 549, 58% women, 66% non-Latinx white) self-reported weight in 2015 and 2018 and completed an accelerometer protocol for seven days. Sedentary time, sleep, light, moderate, and vigorous intensity physical activity (PA) were treated as a compositional variable and multiple linear regression was used to examine associations between activity composition and weight change stratified by sex and race/ethnicity. Compositional isotemporal substitution analysis was used to quantify change in weight associated with reallocating 30 min./day. RESULTS: Activity composition was associated with weight change among women (p = 0.007), but not men (p = 0.356), and among Latinx (p = 0.032) and white participants (p = 0.001), but not Black participants (p = 0.903). Replacement of 30 min./day sedentary time with moderate-vigorous PA was associated with 3.49 lbs. loss (-6.76, -0.22) in Latinx participants and replacement with sleep was associated with 1.52 (0.25, 2.79) and 1.31 (0.40, 2.21) lbs. gain in white women and men. CONCLUSION: The distribution of time spent in daily behaviors was associated with three-year weight change in women, Latinx, and white participants. This was the first longitudinal compositional study of weight change; thus, more studies are needed.

Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants.

BACKGROUND: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. METHODS: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. RESULTS: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. CONCLUSION: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Joint associations of physical activity and body mass index with the risk of established excess body fatness-related cancers among postmenopausal women.

PURPOSE: Excess body fatness and physical activity independently influence the risk of several types of cancer. However, few studies have examined whether physical activity mitigates the excess risk associated with higher body mass index (BMI). METHODS: We examined the individual and joint associations between BMI (kg/m2) and leisure-time moderate-to-vigorous physical activity (MVPA, MET-hours/week) with the risk of three established excess body fatness-related cancers (breast, colon, and endometrial) among 43,795 postmenopausal women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort (1992/1993-2015). Further exclusions for women without an intact uterus resulted in 31,805 women for endometrial cancer analyses. Multivariable Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CIs) with interaction terms to assess multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction. RESULTS: BMI and MVPA were individually associated with breast and endometrial cancer risk, but only BMI was associated with colon cancer risk. In joint analyses, increasing levels of MVPA did not lower the risk of these cancers among obese women. For example, compared to the common referent (BMI 18.5- < 25 kg/m2, MVPA > 0- < 7.5 MET-hours/week), BMI ≥ 30 kg/m2 was associated with a higher risk of breast cancer among women with low MVPA (> 0-< 7.5 MET-hours/week: HR = 1.42, 95% CI: 1.22 - 1.67) and high MVPA (≥ 15 MET-hours/week: HR = 1.53, 95% CI: 1.25 - 1.87; RERI = 0.20, 95% CI: -0.14, 0.54, multiplicative Pinteraction = 0.64). CONCLUSION: Our results do not support the hypothesis that leisure-time physical activity mitigates the excess risk associated with higher BMI for risk of breast, endometrial, or colon cancer among postmenopausal women.

Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies.

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (P trend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.

BACKGROUND: The association between coffee consumption and colorectal cancer risk generally appears null, but recent evidence suggests that risk may vary by coffee type. We examined associations of caffeinated and decaffeinated coffee intake with colorectal cancer risk overall and with colon and rectum separately, among older U.S. men and women. METHODS: In 1999, 47,010 men and 60,051 women with no previous diagnosis of cancer, aged 47-96 years, in the Cancer Prevention Study-II Nutrition Cohort completed a food frequency questionnaire that assessed caffeinated and decaffeinated coffee intake; consumption was updated in 2003. A total of 1829 colorectal cancer cases were verified through June 2015. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking history, alcohol, caffeinated/decaffeinated coffee intake (depending on the model), and other colorectal cancer risk factors. RESULTS: Consumption of ≥2 cups/day of decaffeinated coffee, compared to no decaffeinated coffee, was associated with lower risk of overall colorectal cancer (HR = 0.82, 95% CI: 0.69-0.96, P-trend = 0.04), colon cancer (HR = 0.82, 95% CI: 0.69-0.99, P-trend = 0.05) and rectal cancer (HR = 0.63, 95% CI: 0.40-0.99, P-trend = 0.17). Consumption of ≥2 cups/day of caffeinated coffee was associated with higher risk of rectal cancer (HR = 1.37, 95% CI: 0.99-1.89, P-trend = 0.04), but not with colorectal or colon cancer. CONCLUSION: In this prospective study, higher intake of decaffeinated coffee was associated with lower risk of colorectal, colon, and rectal cancers. Further study on associations of caffeinated and decaffeinated coffee with colorectal cancer risk by subsite is needed.

Prospective Association of Energy Balance Scores Based on Metabolic Biomarkers with Colorectal Cancer Risk.

BACKGROUND: Energy balance-related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear. METHODS: We used reduced rank regression to derive three energy balance scores that associate lifestyle factors with combinations of prediagnostic, circulating levels of high-sensitivity C-reactive protein (hsCRP), C-peptide, and hemoglobin A1c (HbA1c) among 2,498 participants in the Cancer Prevention Study-II Nutrition Cohort. Among 114,989 participants, we verified 2,228 colorectal cancer cases. We assessed associations of each score with colorectal cancer incidence and by tumor molecular phenotypes using Cox proportional hazards regression. RESULTS: The derived scores comprised BMI, physical activity, screen time, and 14 food groups, and explained 5.1% to 10.5% of the variation in biomarkers. The HR and 95% confidence interval (CI) for quartile 4 versus 1 of the HbA1c+C peptide-based score and colorectal cancer was 1.30 (1.15-1.47), the hsCRP-based score was 1.35 (1.19-1.53), and the hsCRP, C-peptide, and HbA1c-based score was 1.35 (1.19-1.52). The latter score was associated with non-CIMP tumors (HRQ4vsQ1: 1.59; 95% CI: 1.17-2.16), but not CIMP-positive tumors (P heterogeneity = 0.04). CONCLUSIONS: These results further support hypotheses that systemic biomarkers of metabolic health-inflammation and abnormal glucose homeostasis-mediate part of the relationship between several energy balance-related modifiable factors and colorectal cancer risk. IMPACT: Results support cancer prevention guidelines for maintaining a healthful body weight, consuming a healthful diet, and being physically active. More research is needed on these clusters of exposures with molecular phenotypes of tumors.

Day-to-day regularity in breakfast consumption is associated with weight status in a prospective cohort of women.

BACKGROUND: Evidence suggests that regular eating patterns (i.e., consistent day-to-day frequency and timing of consumption) may be favorable with respect to weight status, and breakfast may be a particularly important meal for weight maintenance. We examined the relationship between regular breakfast consumption habits and weight status among women. MATERIALS AND METHODS: Modified Poisson regression models examined day-to-day regularity in breakfast consumption among 46,037 women in the prospective Sister Study cohort in relation to weight status. Cross-sectional outcomes included overweight (body mass index (BMI) ≥ 25.0 kg/m2) and obesity (BMI ≥ 30.0 kg/m2); waist circumference (WC) ≥ 88 cm; and waist-to-hip ratio (WHR) ≥ 0.85. Self-reported weight 5 years post-baseline was used to calculate 5 kg weight gain and incident overweight and obesity using BMI. RESULTS: Compared to women who reported eating breakfast 3 to 4 days/week (irregular breakfast eaters), women who ate breakfast 7 days/week were between 11% to 17% less likely to be obese as measured by WHR (prevalence ratio (PR): 0.89; 95%CI: 0.85, 0.94), WC (PR: 0.85; 95%CI: 0.82, 0.88), and BMI (PR: 0.83; 95%CI: 0.79, 0.87) after multivariable adjustment. Women who never ate breakfast were between 11% to 22% less likely to be obese as measured by WHR (PR: 0.89; 95%CI: 0.83, 0.96), WC (PR: 0.82; 95%CI: 0.78, 0.87), and BMI (PR: 0.78; 95%CI: 0.72, 0.84) compared to irregular breakfast eaters. Prospective analyses showed a 21% and 28% lower risk of 5-year incident obesity among participants who always (relative risk (RR): 0.79; 95%CI: 0.70, 0.90) or never (RR: 0.72; 95%CI: 0.59, 0.87) ate breakfast, respectively, compared to those who ate breakfast 3 to 4 days/week. No association was observed for incident 5 kg weight gain. CONCLUSIONS: Results suggest that a regular breakfast consumption habit, comprising eating breakfast every day or never, may be important for maintaining a healthy weight.

Irregularity in breakfast consumption and daily meal timing patterns in association with body weight status and inflammation.

Irregular breakfast consumption and food timing patterns in relation to weight status and inflammation were investigated in a cross-sectional manner among 644 participants in the Cancer Prevention Study-3 Diet Assessment Sub-study. Breakfast consumption, and the individual means and the intra-individual standard deviation (isd) of time at first intake of the day, duration of daily intake window and midpoint of daily intake window were collected via six 24-h recalls and examined in relation to BMI, waist circumference (WC) and inflammation (glycoprotein acetyl (GlycA)). Compared with consuming breakfast on all six recalls, linear regression models showed those who consumed breakfast on 4 or 5 of the days had a 1·29 (95 % CI 0·19, 2·38) and 1·64 (95 % CI 0·12, 3·16) kg/m2 higher BMI; no association was found for consuming breakfast ≤3 d. At 1 h later, the average time of first intake was associated with a 0·44 (95 % CI 0·04, 0·84) kg/m2 higher BMI. A 1-h increase in the isd of first intake was associated with a 1·12 (95 % CI 0·49, 1·75) kg/m2 higher BMI; isd in duration and midpoint of intake window were significant prior to additional adjustment for isd in the first intake. One-hour increases in isd for the first intake time (ß: 0·15; 95 % CI 0·04, 0·26) and the midpoint of intake window (ß: 0·16; 95 % CI 0·02, 0·31) were associated with higher GlycA. No associations were observed for WC independent of BMI. The results provide evidence that irregularity in breakfast consumption and daily intake timing patterns, particularly early in the day, may be related to weight status and inflammation.

Adiposity does not modify the effect of the dietary inflammatory potential on type 2 diabetes incidence among a prospective cohort of men.

PURPOSE: Inflammatory contributions from diet and adiposity may interact with respect to the development of type 2 diabetes mellitus (T2DM). We investigated the degree to which adiposity modified the association between dietary inflammatory potential and incident T2DM. METHODS: Data from 6,016 US men in the Aerobics Center Longitudinal Study who completed a 3-day diet record were used. The inflammatory potential of diet was characterized by the Dietary Inflammatory Index (DII®), and adiposity was assessed with body mass index, waist circumference, body fat percentage (BF) and waist-to-height ratio. Inverse probability weights were used in modified Poisson regression models to examine whether adiposity modifies the relationship between the DII and T2DM, while accounting for selection bias from participants who were lost to follow-up. RESULTS: There were 336 incident cases of T2DM after a mean follow-up of 6.5 years. DII scores were not significantly associated with T2DM incidence in multivariable models, but point estimates were consistently elevated across increasing DII quartiles compared to the most anti-inflammatory DII quartile. In the model that evaluated BF, the term for overall effect modification was significant (p = 0.02), but there was no evidence of effect modification on the multiplicative and additive scales when examined further. Effect modification was not present for any other adiposity measures. CONCLUSIONS: We did not observe evidence that a pro-inflammatory diet, as measured by the DII, is associated with incidence of T2DM, nor evidence that adiposity modifies a potential relationship. Further investigation is needed in larger cohorts with longer follow-up.

Associations of Pre- and Postdiagnosis Diet Quality With Risk of Mortality Among Men and Women With Colorectal Cancer.

PURPOSE: Dietary patterns, indicators of overall diet quality, are associated with colorectal cancer (CRC) incidence but less consistently with mortality among CRC survivors. We prospectively evaluated associations of diet quality pre- and postdiagnosis with risk of mortality among men and women with CRC. PATIENTS AND METHODS: In the Cancer Prevention Study-II Nutrition Cohort, 2,801 participants were cancer free at baseline in 1992/1993 and subsequently diagnosed with invasive, nonmetastatic CRC during follow-up through June 2013. Pre- and postdiagnosis diet data were available for 2,671 and 1,321 participants, respectively, among whom 1,414 and 722 died. Concordance with the Dietary Approaches to Stop Hypertension (DASH), American Cancer Society nutrition guidelines (ACS-score), prudent, and Western dietary patterns was used to evaluate diet quality. RESULTS: Extreme scoring group comparisons showed that prediagnosis ACS-score was inversely associated with all-cause (hazard ratio high v low [HRHigh vLow], 0.78; 95% CI, 0.65 to 0.95) and CRC-specific (HRHigh vLow, 0.74; 95% CI, 0.54 to 1.03) mortality, whereas the Western diet score was associated with higher all-cause mortality (HRHigh vLow, 1.30; 95% CI, 1.03 to 1.64). For postdiagnosis diet, the ACS-score was associated with lower risk of all-cause (HRHigh vLow, 0.62; 95% CI, 0.47 to 0.83) and CRC-specific (HRHigh vLow, 0.35; 95% CI, 0.17 to 0.73) mortality, the DASH score was inversely associated with all-cause (HRHigh vLow, 0.79; 95% CI, 0.62 to 0.99) and CRC-specific (HRHigh vLow, 0.56; 95% CI, 0.35 to 0.89) mortality, and the prudent score was inversely associated with all-cause mortality (HRHigh vLow, 0.72; 95% CI, 0.56 to 0.93). Among participants with a low diet quality before diagnosis, improved DASH (HR, 0.54; 95% CI, 0.31 to 0.92) and prudent (HR, 0.53; 95% CI, 0.29 to 0.95) scores from pre- to postdiagnosis were inversely associated with CRC-specific mortality. CONCLUSION: Dietary patterns reflective of high intakes of plant foods and low intakes of animal products before and after CRC diagnosis are associated with longer survival.

An Estrogen-Related Dietary Pattern and Postmenopausal Breast Cancer Risk in a Cohort of Women with a Family History of Breast Cancer.

Background: The results of previous studies on diet and postmenopausal breast cancer risk have been inconclusive, but there is some evidence that dietary patterns developed to correlate with estrogen levels are associated with breast cancer. We aimed to examine the association of a previously developed estrogen-related dietary pattern (ERDP) with postmenopausal breast cancer in the Sister Study.Methods: The ERDP was calculated from food frequency questionnaire responses among Sister Study participants without a personal history of cancer and who contributed postmenopausal person-time at risk. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the association between the ERDP and postmenopausal breast cancer.Results: With more than 261,959 person-years of follow-up and 1,968 incident cases, the ERDP was not associated with total, invasive, estrogen receptor (ER)-positive or ER-negative subtypes of breast cancer. Results were robust to various sensitivity analyses.Conclusions: The results do not support previous studies observing a positive association between a proestrogenic dietary pattern and postmenopausal breast cancer risk. Null results may be partially explained by high levels of other breast cancer risk factors within the study population, such as a family history of breast cancer.Impact: An estrogen-related dietary pattern may not be a strong predictor of breast cancer risk in all populations. Future studies of diet and breast cancer should evaluate the potential for effect modification by family history and consider differences in dietary assessment tools when comparing results across study populations. Cancer Epidemiol Biomarkers Prev; 27(10); 1223-6. ©2018 AACR.

An estrogen-related lifestyle score is associated with risk of postmenopausal breast cancer in the PLCO cohort.

PURPOSE: Healthy or unhealthy lifestyle behaviors are often adopted together. We aimed to investigate the combined effect of estrogen-related lifestyle factors on postmenopausal breast cancer risk. METHODS: Data from 27,153 women enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were used. We created an estrogen-related lifestyle score (ERLS) by incorporating a previously developed measure of estrogenic diet, alcohol intake, body mass index (BMI), and physical activity. The scores ranged from 0 to 6 with alcohol and BMI accounting for higher weights than the other factors. To evaluate the preventive possibilities of a low estrogen-related lifestyle and to be consistent with other published lifestyle scores, higher scores were set to correspond with potentially lower estrogenic lifestyle. The association between the ERLS and incident breast cancer was examined using Cox proportional hazards models. RESULTS: Participants with an ERLS of 4 or ≥ 5 had a 23% (HR 0.77; 95% CI 0.67-0.89) and 34% (HR 0.66; 95% CI 0.56-0.78) lower risk of breast cancer, respectively, compared to those with an ERLS ≤ 2 after multivariable adjustment. Estimates were similar when restricting to invasive cases or estrogen receptor-positive subtypes. No single lifestyle component appeared to drive the association. CONCLUSIONS: Our findings suggest that the combined effect of a lifestyle characterized by a low estrogenic diet, low alcohol consumption, low body weight, and high levels of physical activity are associated with a reduction in postmenopausal breast cancer risk, possibly through an influence on estrogen metabolism.

A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women.

Increased exposure to estrogen is a risk factor for postmenopausal breast cancer, and dietary factors can influence estrogen metabolism. However, studies of diet and breast cancer have been inconclusive. We developed a dietary pattern associated with levels of unconjugated estradiol and the ratio of 2- and 16-hydroxylated estrogen metabolites in a subsample of Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) participants (n = 653) using reduced rank regression, and examined its association with postmenopausal breast cancer prospectively in the larger PLCO cohort (n = 27,488). The estrogen-related dietary pattern (ERDP) was comprised of foods with positively-weighted intakes (non-whole/refined grains, tomatoes, cruciferous vegetables, cheese, fish/shellfish high in ω-3 fatty acids, franks/luncheon meats) and negatively-weighted intakes (nuts/seeds, other vegetables, fish/shellfish low in ω-3 fatty acids, yogurt, coffee). A 1-unit increase in the ERDP score was associated with an increase in total (HR: 1.09, 95% CI: 1.01-1.18), invasive (HR: 1.13; 95% CI: 1.04-1.24) and estrogen receptor (ER)-positive (HR: 1.13, 95% CI: 1.02-1.24) breast cancer risk after adjustment for confounders. Associations were observed for the fourth quartile of ERDP compared with the first quartile for overall breast cancer (HR: 1.14; 95% CI: 0.98-1.32), invasive cases (HR: 1.20, 95% CI: 1.02-1.42) and ER-positive cases (HR: 1.19; 95% CI: 0.99-1.41). The increased risk associated with increasing ERDP score was more apparent in strata of some effect modifiers (postmenopausal hormone therapy non-users and non-obese participants) where the relative estrogen exposure due to that factor was lowest, although the p values for interaction were not statistically significant. Results suggest a dietary pattern based on estrogen metabolism is positively associated with postmenopausal breast cancer risk, possibly through an estrogenic influence.