Coffee consumption is associated with a reduced risk of colorectal cancer recurrence and all-cause mortality.

Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I-III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self-reported using questionnaires at the time of diagnosis. We retrieved recurrence and all-cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2-year median follow-up and 309 deaths during a 6.6-year median follow-up. Consuming more than 4 cups/d of coffee compared to an intake of <2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all-cause mortality was U-shaped; coffee intake seemed optimal at 3-5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all-cause mortality. The association between coffee consumption and all-cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.

Reproducibility and dietary correlates of plasma polyphenols in the JPHC-NEXT Protocol Area study.

BACKGROUND: In recent years, an increasing number of epidemiological studies have suggested a role of polyphenols in the prevention of chronic diseases. Prospective cohort studies have typically measured polyphenol concentrations in a single blood sample and the reproducibility of plasma polyphenol measurements is largely unknown. OBJECTIVE: We evaluated the reproducibility of 35 plasma polyphenols collected at an interval of 1-year. We also examined correlations of these polyphenols with food group intakes calculated from weighed food records (WFR) and food frequency questionnaire (FFQ). METHODS: The study included 227 middle-aged participants from the JPHC-NEXT Protocol Area in Japan. We measured 35 polyphenols in plasma collected at two points 1-year apart. Food group intakes were calculated from 12-day WFR and FFQ. For the reproducibility analysis, the intraclass correlation coefficient (ICC) of 35 polyphenol concentrations were examined between the two points. Pearson's partial correlations was used to assess the correlation between polyphenols and food groups. RESULTS: Moderate- to high ICCs were observed for tea-originated polyphenols such as gallic acid, quercetin, epigallocatechin, and kaempferol - and coffee-derived polyphenols, such as caffeic acid, and ferulic acid. For the dietary analyses, moderate correlations were observed for non-alcoholic beverages intake and epigallocatechin, epicatechin, catechin, and gallic acid. For green tea, higher correlations were observed with these polyphenols. CONCLUSION: Plasma concentrations of tea and coffee-related polyphenols, except for catechin, had good reproducibility over a 1-year period. The correlations between intake of non-alcoholic beverages, particularly green tea, and tea polyphenols, indicated moderate- to high correlations.

Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. RESULTS: Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). CONCLUSIONS: Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis.

Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.

Genome-wide interaction analysis of folate for colorectal cancer risk.

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

The association between genetically elevated polyunsaturated fatty acids and risk of cancer.

BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding. INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. FUNDING: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.

Dietary Ruminant and Industrial Trans-Fatty Acids Intake and Colorectal Cancer Risk.

As colorectal cancer (CRC) is largely due to modifiable lifestyle habits, the awareness on its risk factors is highly important. Dietary fatty acids have been linked to CRC risk. We explored the association between dietary trans fatty acids (TFAs) intake and CRC risk. We analyzed 865 CRC cases (434 in colon and 404 in rectum) and 3206 controls of the IROPICAN study, with data collected by trained interviewers using validated questionnaires. TFAs intake (industrial and ruminant types) was categorized into quartiles. Multivariate logistic regression models were built to calculate the odds ratios (OR) for the association between CRC and TFAs. We observed a positive association between industrial TFAs and colon cancer (OR for highest vs lowest quartile [ORQ4vsQ1] = 1.28, 95% confidence interval 1.07-1.54). A higher association was observed between industrial TFAs and CRC, occurring after 50 years of age. In addition, elaidic acid was associated with an increased risk of colon (ORQ4vsQ1 = 1.58, 1.24-2.02) and specifically of proximal colon cancer (OR Q4vsQ1 = 2.12, 1.40-3.20), as well as of rectum cancer (ORQ4vsQ1 = 1.40, 1.07-1.83). An inverse association was observed between ruminant TFAs intake and colon cancer risk (ORQ4vsQ1 = 0.80, 0.67-0.97). Industrial TFAs, such as semisolid/solid hydrogenated oils, may increase the risk of CRC, especially colon and proximal colon cancer. In contrast, ruminant TFAs do not appear to be associated with CRC. Awareness programs and regulatory actions regarding hydrogenated oils are warranted, given their high consumption through ultra-processed foods in more developed and less developed countries.

Prediagnostic plasma polyphenol concentrations and colon cancer risk: The JPHC nested case-control study.

BACKGROUND & AIMS: Epidemiological studies that assessed the associations between dietary polyphenol intakes and colon cancer risk have reported largely null results, possibly due to measurement error associated with dietary assessment. We adopted an objective approach by measuring prediagnostic plasma concentrations of 35 polyphenols and assessing associations with colon cancer risk. METHODS: We conducted a nested-case control study within the Japan Public Health Center-based prospective study (JPHC Study) utilizing plasma samples collected at the time of a five-year follow-up survey between 1995 and 1999. We identified colon cancer cases who developed cancer during the follow-up from the time of blood collection. Controls were matched by age, sex, area code, population size of the area, season of blood collection, year of blood collection, and duration of fasting time before the blood collection. Prediagnostic concentrations of 35 polyphenols from 375 incident colon cancer cases (followed until 2012) and 710 matched controls were measured by tandem mass spectrometry coupled with ultra-high-pressure liquid chromatography. We used multivariable conditional logistic regression models adjusted for established colon cancer risk factors to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In sexes combined log2-transformed multivariable models, circulating levels of 3,4-dihydroxyphenylpropionic acid (P = 0.02), ferulic acid (P = 0.02), and caffeic acid (P = 0.03) were inversely, and 3-hydroxybenzoic acid (P = 0.03) was positively, associated with colon cancer risk. For men only, circulating levels of 3,4-dihydroxyphenylpropionic acid was inversely, and 3,5-dihydroxyphenylpropionic acid, gallic acid, (+)-epigallocatechin, 3-hydroxybenzoic acid, and epicatechin were positively, associated with colon cancer risk. In women, plasma caffeic acid and ferulic acid concentration were inversely associated with colon cancer risk. However, all these associations were nonsignificant after adjustment for multiple comparisons. The remaining polyphenols were not associated with colon cancer risk. CONCLUSION: Coffee-derived 3,4-dihydroxyphenylpropionic acid, ferulic acid, and caffeic acid concentrations were inversely associated with colon cancer risk although the association were nonsignificant after adjustment for multiple comparisons. These results support a possible role of coffee polyphenols in preventing colorectal cancer.

Dietary fats and their sources in association with the risk of bladder cancer: A pooled analysis of 11 prospective cohort studies.

The effects of fat intake from different dietary sources on bladder cancer (BC) risk remains unidentified. Therefore, the present study aimed to investigate the association between fat intakes and BC risk by merging world data on this topic. Data from 11 cohort studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study, provided sufficient information on fat intake for a total of 2731 BC cases and 544 452 noncases, which yielded 5 400 168 person-years of follow-up. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox-regression models stratified on cohort. Analyses were adjusted for total energy intake in kilocalories, gender, smoking status (model-1) and additionally for sugar and sugar products, beers, wine, dressing and plant-based and fruits intakes (model-2). Among women, an inverse association was observed between mono-unsaturated fatty acids (MUFAs) and BC risk (HR comparing the highest with the lowest tertile: 0.73, 95% CI: 0.58-0.93, P-trend = .01). Overall, this preventative effect of MUFAs on BC risk was only observed for the nonmuscle invasive bladder cancer (NMIBC) subtype (HR: 0.69, 95% CI: 0.53-0.91, P-trend = .004). Among men, a higher intake of total cholesterol was associated with an increased BC risk (HR: 1.37, 95% CI: 1.16-1.61, P-trend = .01). No other significant associations were observed. This large prospective study adds new insights into the role of fat and oils in BC carcinogenesis, showing an inverse association between consumption of MUFAs and the development of BC among women and a direct association between higher intakes of dietary cholesterol and BC risk among men.

Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling  = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites.

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.

NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles.

Metabolomics may help to elucidate mechanisms underlying diet-disease relationships and identify novel risk factors for disease. To inform the design and interpretation of such research, evidence on diet-metabolite associations and cross-assay comparisons is needed. We aimed to compare nuclear magnetic resonance (NMR) metabolite profiles between meat-eaters, fish-eaters, vegetarians and vegans, and to compare NMR measurements to those from mass spectrometry (MS), clinical chemistry and capillary gas-liquid chromatography (GC). We quantified 207 serum NMR metabolite measures in 286 male participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Using univariate and multivariate analyses, we found that metabolite profiles varied by diet group, especially for vegans; the main differences compared to meat-eaters were lower levels of docosahexaenoic acid, total n-3 and saturated fatty acids, cholesterol and triglycerides in very-low-density lipoproteins, various lipid factions in high-density lipoprotein, sphingomyelins, tyrosine and creatinine, and higher levels of linoleic acid, total n-6, polyunsaturated fatty acids and alanine. Levels in fish-eaters and vegetarians differed by metabolite measure. Concentrations of 13 metabolites measured using both NMR and MS, clinical chemistry or GC were mostly similar. In summary, vegans' metabolite profiles were markedly different to those of men consuming animal products. The studied metabolomics platforms are complementary, with limited overlap between metabolite classes.

Tea Drinking and Risk of Cancer Incidence: A Meta-Analysis of Prospective Cohort Studies and Evidence Evaluation.

Here we provide a comprehensive meta-analysis to summarize and appraise the quality of the current evidence on the associations of tea drinking in relation to cancer risk. PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched up to June 2020. We reanalyzed the individual prospective studies focused on associations between tea drinking and cancer risk in humans. We conducted a meta-analysis of prospective studies and provided the highest- versus lowest-category analyses, dose-response analyses, and test of nonlinearity of each association by modeling restricted cubic spline regression for each type of tea. We graded the evidence based on the summary effect size, its 95% confidence interval, 95% prediction interval, the extent of heterogeneity, evidence of small-study effects, and excess significance bias. We identified 113 individual studies investigating the associations between tea drinking and 26 cancer sites including 153,598 cancer cases. We assessed 12 associations for the intake of black tea with cancer risk and 26 associations each for the intake of green tea and total tea with cancer risk. Except for an association between lymphoid neoplasms with green tea, we did not find consistent associations for the highest versus lowest categories and dose-response analyses for any cancer. When grading current evidence for each association (number of studies ≥2), weak evidence was detected for lymphoid neoplasm (green tea), glioma (total tea, per 1 cup), bladder cancer (total tea, per 1 cup), and gastric and esophageal cancer (tea, per 1 cup). This review of prospective studies provides little evidence to support the hypothesis that tea drinking is associated with cancer risk. More well-designed studies are still needed to identify associations between tea intake and rare cancers.

Genetically predicted circulating concentrations of micronutrients and risk of breast cancer: A Mendelian randomization study.

The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micronutrients and breast cancer risk. We investigated associations between genetically predicted concentrations of 11 micronutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6 , vitamin B12 and zinc) and breast cancer risk using Mendelian randomization (MR). A two-sample MR study was conducted using 122 977 women with breast cancer and 105 974 controls from the Breast Cancer Association Consortium. MR analyses were conducted using the inverse variance-weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions. A value of 1 SD (SD: 0.08 mmol/L) higher genetically predicted concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10-1.25, P value = 9.1 × 10-7 ) and 20% (OR: 1.20, 95% CI: 1.08-1.34, P value = 3.2 × 10-6 ) higher risk of overall and ER+ve breast cancer, respectively. An inverse association was observed for a SD (0.5 mg/dL) higher genetically predicted phosphorus concentration and ER-ve breast cancer (OR: 0.84, 95% CI: 0.72-0.98, P value = .03). There was little evidence that any other nutrient was associated with breast cancer. The results for magnesium were robust under all sensitivity analyses and survived correction for multiple comparisons. Higher circulating concentrations of magnesium and potentially phosphorus may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms.

Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies.

BACKGROUND: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. RESULTS: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. CONCLUSIONS: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.

Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose-response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex (P-interaction < 0.001) and smoking (P-interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27-2.42, P-trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12-1.85, P-trend = 0.001). In addition, dose-response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06-1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort.

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC.

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.