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Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Harewood, R, Rothwell, JA, Bešević, J, Viallon, V, Achaintre, D, Gicquiau, A, Rinaldi, S, Wedekind, R, Prehn, C, Adamski, J, et al
EBioMedicine. 2024;:105024
Abstract
BACKGROUND Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. INTERPRETATION Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FUNDING World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).
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Metabolome biomarkers linking dietary fibre intake with cardiometabolic effects: results from the Danish Diet, Cancer and Health-Next Generations MAX study.
Unión-Caballero, A, Meroño, T, Zamora-Ros, R, Rostgaard-Hansen, AL, Miñarro, A, Sánchez-Pla, A, Estanyol-Torres, N, Martínez-Huelamo, M, Cubedo, M, González-Domínguez, R, et al
Food & function. 2024;(3):1643-1654
Abstract
Biomarkers associated with dietary fibre intake, as complements to traditional dietary assessment tools, may improve the understanding of its role in human health. Our aim was to discover metabolite biomarkers related to dietary fibre intake and investigate their association with cardiometabolic risk factors. We used data and samples from the Danish Diet Cancer and Health Next Generation (DCH-NG) MAX-study, a one-year observational study with evaluations at baseline, six and 12 months (n = 624, 55% female, mean age: 43 years, 1353 observations). Direct associations between fibre intake and plasma concentrations of 2,6-dihydroxybenzoic acid (2,6-DHBA) and indolepropionic acid were observed at the three time-points. Both metabolites showed an intraclass-correlation coefficient (ICC) > 0.50 and were associated with the self-reported intake of wholegrain cereals, and of fruits and vegetables, respectively. Other metabolites associated with dietary fibre intake were linolenoyl carnitine, 2-aminophenol, 3,4-DHBA, and proline betaine. Based on the metabolites associated with dietary fibre intake we calculated predicted values of fibre intake using a multivariate, machine-learning algorithm. Metabolomics-based predicted fibre, but not self-reported fibre values, showed negative associations with cardiometabolic risk factors (i.e. high sensitivity C-reactive protein, systolic and diastolic blood pressure, all FDR-adjusted p-values <0.05). Furthermore, different correlations with gut microbiota composition were observed. In conclusion, 2,6-DHBA and indolepropionic acid in plasma may better link dietary fibre intake with its metabolic effects than self-reported values. These metabolites may represent a novel class of biomarkers reflecting both dietary exposure and host and/or gut microbiota characteristics providing a read-out that is differentially related to cardiometabolic risk.
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Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.
Hughes, DJ, Schomburg, L, Jenab, M, Biessy, C, Méplan, C, Moskal, A, Sun, Q, Demircan, K, Fedirko, V, Weiderpass, E, et al
Free radical biology & medicine. 2023;(Pt 2):381-393
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Abstract
Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.
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Long-term air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts.
Hvidtfeldt, UA, Chen, J, Rodopoulou, S, Strak, M, de Hoogh, K, Andersen, ZJ, Bellander, T, Brandt, J, Fecht, D, Forastiere, F, et al
British journal of cancer. 2023;(4):656-664
Abstract
BACKGROUND Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown. METHODS We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0-191.9/C71.0-C71.9, 192.0/C72.2-C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 μg/m³ NO2, 1.17 (0.96, 1.41) per 5 μg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10-5m-1 BC, and 0.99 (0.84, 1.17) per 10 μg/m³ O3. CONCLUSIONS We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.
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Dietary polyphenols, metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort.
Lanuza, F, Zamora-Ros, R, Bondonno, NP, Meroño, T, Rostgaard-Hansen, AL, Riccardi, G, Tjønneland, A, Landberg, R, Halkjær, J, Andres-Lacueva, C
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2023;33(6):1167-1178
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Metabolic syndrome (MetS) is a cluster of metabolic disorders that increases the risk of developing chronic diseases. Cardiometabolic risk factors include high waist circumference (WC), insulin resistance, hypertension, dysglycaemia, dyslipidaemia, and altered inflammatory markers. The aim of this study was to investigate the associations between intakes of polyphenols (total polyphenols and their main classes) and the prevalence of MetS and cardiometabolic risk factors. This study is an observational sub-cohort study of 676 Danish participants of the MAX study from the Danish Diet, Cancer and Health - Next Generations (DCH-NG) cohort. Results showed that individuals with higher total polyphenol and phenolic acid intakes, were less likely to have MetS. Furthermore, for cardiovascular risk factors, intakes of total polyphenols, flavonoids and phenolic acids were associated with a lower risk of higher systolic blood pressure and lower high-density lipoprotein cholesterol. Authors conclude by suggesting that intervention studies should be undertaken to establish whether a polyphenol-rich diet can improve some cardiometabolic risk factors and can reduce or delay the onset of cardiometabolic diseases in free-living populations.
Abstract
BACKGROUND AND AIMS Polyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health-Next Generations (DCH-NG) cohort. METHODS AND RESULTS Dietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 - for total polyphenols, flavonoids and phenolic acids-had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05). CONCLUSIONS Total polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.
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Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.
Morales-Berstein, F, Biessy, C, Viallon, V, Goncalves-Soares, A, Casagrande, C, Hémon, B, Kliemann, N, Cairat, M, Blanco Lopez, J, Al Nahas, A, et al
European journal of nutrition. 2023
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Expert Review
Conflicts of interest:
None
Take Home Message:
UPF intake influences incidence of cancers of the head, neck and oesophagus, this impact appears to be regardless of their impact on adiposity.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study evaluated the relationship between consumption of ultra-processed foods and risk of developing cancer of the head and neck (HNC) and oesophagus (OAC), and the role of adiposity in this relationship.
Methods
- Data from the EPIC study including 450111 participants from 10 countries with a mean follow-up duration 14.13 + 3.98 years
- Dietary intakes evaluated using validated questionnaires
- Dietary intakes analysed by firstly identifying ingredients from meals, whether home-made or elsewhere. These components then analysed using NOVA classification of food by extent of processing. NOVA 1 - minimally processed natural foods; NOVA 2 - culinary ingredients e.g. oil, butter, salt, derived from NOVA1 foods with minimal processing; NOVA 3 - industrial products, containing both processed and unprocessed or minimally processed components; NOVA 4 - processed foods not normally used in domestic kitchens, additives intended to enhance taste and/or attractiveness to consumers
- NOVA 3 and 4 foods considered ultra-processed foods (UPF)
- Cancers of the oesophagus, oral cavity, larynx, and pharynx identified from registries, insurance records, and direct follow up
- Participant age, level of education and physical activity were also collected. Height, weight, waist and hip circumference used to calculate BMI and waist to hip ratio (WHR)
- Cox proportional hazards models used to calculate Hazard Ratios (HR. for associations between food intake, cancer incidence and participant characteristics
- Data adjusted for alcohol intake and smoking status.
Results
- 70.8% participants female, mean age at recruitment 51.1 years
- . Mean UPF consumption (g/d) and percentage of total dietary intake varied between countries, from 13.7% (363 g/d) in Spain to 18.6% (520.5 g/d) in the UK
- Male participants had higher mean UPF intake than females, 14.7% versus 13.3% of diet
- Higher UPF intake was associated with increased risk of cancer. For HNC 10% increase in UPF = HR 1.23 (95% CI 1.14-1.34). For OAC HR =1.24 (95% CI = 1.05-1.47
- Greatest effect was seen for cancers of the hypopharynx
- Increased risk was not explained by adiposity: only 5% increased risk for HNC was associated with WHR and 13% increased OAC risk attributable to BMI and WHR.
Conclusion
UPF consumption is associated with increased risks of HNC and OAC, by mechanisms other than increased adiposity.
Clinical practice applications:
- People at risk of HNC or OAC should be made aware of the evidence here of additional risks of consuming UPF
- Although increased adiposity, smoking and consumption of alcohol have some impact on incidence of these cancers, UPF consumption appears to act through some other mechanisms
- Clear definitions of degrees of food processing are provided by this study.
Considerations for future research:
Further areas are worth exploring:
- The impact on UPF intake on the intake of other food groups, for example was UPF intake associated with decreased intake of fruit and vegetables?
- The impact of UPF intake on oral and oesophageal microbiome composition could be considered.
Abstract
PURPOSE To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).
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A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.
Sobiecki, JG, Imamura, F, Davis, CR, Sharp, SJ, Koulman, A, Hodgson, JM, Guevara, M, Schulze, MB, Zheng, JS, Agnoli, C, et al
PLoS medicine. 2023;20(4):e1004221
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Self-reported adherence to the Mediterranean diet (MedDiet) has been associated with a lower incidence of type 2 diabetes (T2D). However, as no biological indicators of whether people are really following the MedDiet have been recorded, it is difficult to definitively ascertain any associations. This post-hoc analysis of a randomised control trial and a cohort study aimed to determine indicative nutritional biomarkers associated with the MedDiet and to see if associations exist with the incidence of T2D. The study formulated a biomarker score based on 29 different nutrients that are in abundance in the MedDiet. This score was then applied to an observational study and showed that as the score went up and therefore adherence to the diet, the incidence of T2D went down and vice versa. Higher adherence to the MedDiet resulted in an 11% decrease in the incidence of T2D. It was concluded that adherence to the MedDiet may help to prevent T2D. This study could be used by healthcare professionals to recommend the commencement of the MedDiet in individuals who are risk of its development.
Abstract
BACKGROUND Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.
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Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.
Koutros, S, Kiemeney, LA, Pal Choudhury, P, Milne, RL, Lopez de Maturana, E, Ye, Y, Joseph, V, Florez-Vargas, O, Dyrskjøt, L, Figueroa, J, et al
European urology. 2023;(1):127-137
Abstract
BACKGROUND Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. CONCLUSIONS We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. PATIENT SUMMARY We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.
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Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).
Mahamat-Saleh, Y, Al-Rahmoun, M, Severi, G, Ghiasvand, R, Veierod, MB, Caini, S, Palli, D, Botteri, E, Sacerdote, C, Ricceri, F, et al
International journal of cancer. 2023;(3):348-362
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Abstract
Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.
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Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts.
Rothwell, JA, Bešević, J, Dimou, N, Breeur, M, Murphy, N, Jenab, M, Wedekind, R, Viallon, V, Ferrari, P, Achaintre, D, et al
BMC medicine. 2023;(1):80
Abstract
BACKGROUND Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. RESULTS Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. CONCLUSIONS Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.