Publications
580 results found
Bull CJ, Hazelwood E, Bell JA, et al., 2023, Identifying metabolic features of colorectal cancer liability using Mendelian randomization., medRxiv
Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development.
Su Y-R, Sakoda LC, Jeon J, et al., 2023, Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort., Cancer Epidemiol Biomarkers Prev, Vol: 32, Pages: 353-362
BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance. METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group). RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity. CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort. IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.
Kliemann N, Rauber F, Levy R, et al., 2023, Food processing and cancer risk in Europe: results from the prospective EPIC cohort study, The Lancet Planetary Health, Vol: 7, Pages: E219-E232, ISSN: 2542-5196
BackgroundFood processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.MethodsThis study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models.Findings521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95–0·9
Carreras-Torres R, Kim AE, Lin Y, et al., 2023, Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response., Cancer Epidemiol Biomarkers Prev, Vol: 32, Pages: 315-328
BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. IMPACT: These findings can guide potential prevention treatments.
Rothwell JA, Bešević J, Dimou N, et al., 2023, Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts, BMC Medicine, Vol: 21, Pages: 1-13, ISSN: 1741-7015
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.
Yammine SG, Huybrechts I, Biessy C, et al., 2023, Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition., BMC Cancer, Vol: 23, Pages: 1-12, ISSN: 1471-2407
BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Tsilidis KK, Cariolou M, Becerra-Tomas N, et al., 2023, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, Vol: 152, Pages: 635-644, ISSN: 0020-7136
Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
Chan DSM, Vieira R, Abar L, et al., 2023, Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 572-599, ISSN: 0020-7136
Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.
Cariolou M, Abar L, Aune D, et al., 2023, Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 600-615, ISSN: 0020-7136
It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded ‘limited-suggestive’ likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.
Becerra-Tomas N, Balducci K, Abar L, et al., 2023, Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 616-634, ISSN: 0020-7136
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.
Aglago EK, Cross AJ, Riboli E, et al., 2023, Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study, British Journal of Cancer, ISSN: 0007-0920
Castro-Espin C, Bonet C, Crous-Bou M, et al., 2023, Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis: results from a cohort study, British Journal of Cancer, ISSN: 0007-0920
BackgroundInflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.MethodsThe diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.ResultsWe included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.ConclusionsGreater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.
Cross AJ, Gunter MJ, 2023, Ultra-processed foods and colorectal neoplasia: is there a link?, JNCI-Journal of the National Cancer Institute, Vol: 115, Pages: 117-119, ISSN: 0027-8874
Murphy N, Newton CC, Song M, et al., 2023, Body mass index and molecular subtypes of colorectal cancer, Journal of the National Cancer Institute, Vol: 115, Pages: 165-173, ISSN: 0027-8874
BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). CONCLUSIONS: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
Chang C-M, Gunter M, Rauber F, et al., 2023, Ultra-processed food consumption, cancer risk and cancer mortality: a large-scale prospective analysis within the UK Biobank, EClinicalMedicine, Vol: 56, Pages: 1-12, ISSN: 2589-5370
BackgroundGlobal dietary patterns are increasingly dominated by relatively cheap, highly palatable, and ready-to-eat ultra-processed foods (UPFs). However, prospective evidence is limited on cancer development and mortality in relation to UPF consumption. This study examines associations between UPF consumption and risk of cancer and associated mortality for 34 site-specific cancers in a large cohort of British adults.MethodsThis study included a prospective cohort of UK Biobank participants (aged 40–69 years) who completed 24-h dietary recalls between 2009 and 2012 (N = 197426, 54.6% women) and were followed up until Jan 31, 2021. Food items consumed were categorised according to their degree of food processing using the NOVA food classification system. Individuals’ UPF consumption was expressed as a percentage of total food intake (g/day). Prospective associations were assessed using multivariable Cox proportional hazards models adjusted for baseline socio-demographic characteristics, smoking status, physical activity, body mass index, alcohol and total energy intake.FindingsThe mean UPF consumption was 22.9% (SD 13.3%) in the total diet. During a median follow-up time of 9.8 years, 15,921 individuals developed cancer and 4009 cancer-related deaths occurred. Every 10 percentage points increment in UPF consumption was associated with an increased incidence of overall (hazard ratio, 1.02; 95% CI, 1.01–1.04) and specifically ovarian (1.19; 1.08–1.30) cancer. Furthermore, every 10 percentage points increment in UPF consumption was associated with an increased risk of overall (1.06; 1.03–1.09), ovarian (1.30; 1.13–1.50), and breast (1.16; 1.02–1.32) cancer-related mortality.InterpretationOur UK-based cohort study suggests that higher UPF consumption may be linked to an increased burden and mortality for overall and certain site-specific cancers especially ovarian cancer in women.FundingThe Cancer Research UK and World Cancer Re
Ugai T, Akimoto N, Haruki K, et al., 2023, Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases, Journal of Gastroenterology, Vol: 58, Pages: 229245-229245, ISSN: 0944-1174
BACKGROUND: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. METHODS: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. RESULTS: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. CONCLUSIONS: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
Papadimitriou N, Bull CJ, Jenab M, et al., 2023, Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study, BMC Medicine, Vol: 21, Pages: 1-10, ISSN: 1741-7015
BACKGROUND: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. METHODS: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. RESULTS: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). CONCLUSIONS: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
Karavasiloglou N, Hughes DJ, Murphy N, et al., 2023, Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts, The American Journal of Clinical Nutrition, Vol: 117, Pages: 33-45, ISSN: 0002-9165
BACKGROUND: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. OBJECTIVES: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. METHODS: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. RESULTS: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. CONCLUSIONS: In UK-BB, higher serum ionized calcium
Huybrechts I, Rauber F, Nicolas G, et al., 2022, Characterization of the degree of food processing in the European Prospective Investigation into Cancer and Nutrition: Application of the Nova classification and validation using selected biomarkers of food processing, Frontiers in Nutrition, Vol: 9, ISSN: 2296-861X
Background: Epidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.Methods: After grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke u
Sedlmeier AMM, Viallon V, Ferrari P, et al., 2022, Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study, BRITISH JOURNAL OF CANCER, ISSN: 0007-0920
Ugai T, Cao Y, Haruki K, et al., 2022, Molecular characteristics and prognosis of early-onset colorectal cancer according to detailed anatomical locations: Comparison to later-onset cases., CANCER RESEARCH, Vol: 82, ISSN: 0008-5472
Aune D, Markozannes G, Abar L, et al., 2022, Physical activity and health-related quality of life in women with breast cancer: a meta-analysis, JNCI Cancer Spectrum, Vol: 6, Pages: 1-14, ISSN: 2515-5091
Background: Physical activity (PA) is associated with improved health-related quality-of-life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. Methods: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent Expert Panel graded the evidence. Results: Seventy-nine RCTs (14,554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast, WMDs (95% confidence intervals)=5.94 (2.64-9.24, I2=59%, n=12), Functional Assessment of Cancer Therapy-General, 4.53 (1.94-7.13, I2=72%, n=18), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, 6.78 (2.61-10.95, I2=76.3%, n=17). The likelihood of causality was considered probable that PA improves HRqoL in breast cancer survivors. Effects were weaker for physical function and mental/emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. Conclusion: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental/emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.
Chang K, Millett C, Rauber F, et al., 2022, Ultra-processed food consumption, cancer risk, and cancer mortality: a prospective cohort study of the UK Biobank, LANCET, Vol: 400, Pages: 31-31, ISSN: 0140-6736
Chang K, Millett C, Rauber F, et al., 2022, Ultra-processed food consumption, cancer risk, and cancer mortality: a prospective cohort study of the UK Biobank., Lancet, Vol: 400 Suppl 1
BACKGROUND: Dietary patterns worldwide are increasingly displaced by many cheap, highly palatable, and ready-to-eat ultra-processed foods (UPFs). Higher UPF consumption has been linked to increased risk for obesity and cardiometabolic diseases, but prospective evidence is limited on cancer outcomes. This study aimed to examine the association between UPF consumption and risk for overall and site-specific cancer incidence and cancer mortality using the UK Biobank cohort. METHODS: 197 426 participants of the UK Biobank from England, Scotland, and Wales with 24-h dietary recall completed between 2009 and 2012 were included. Incident cancer cases were identified through data linkage to national cancer and mortality registries. Food items consumed were categorised according to their degree of food processing using the NOVA classification system. Individual UPF consumption were derived as a percentage of daily food intake. Prospective association was assessed using multivariable Cox proportional hazards models adjusted for baseline sociodemographic and lifestyle characteristics. For female-specific cancers, menopausal status, use of oral contraceptives, hormone replacement therapy, and parity were additionally adjusted. FINDINGS: Mean age was 58·0 years (SD 8·0); 54·6% of participants were women. During a median follow-up time of 9·8 years (IQR 9·4-10·6), 15 921 (8·1%) of 197 426 individuals developed cancer and 4009 (2·0%) cancer deaths were encountered. Consumption of UPFs was associated with a higher incidence of overall cancer (hazard ratio per 10% increment in UPF consumption was 1·02 [95% CI 1·01-1·04]; p=0·005) and ovarian cancer in females (1·19 [1·08-1·30]; p<0·001). Positive associations were identified for mortality of overall, breast, and ovarian cancers. INTERPRETATION: This large UK cohort study presents evidence of positive associations between
Breeur M, Ferrari P, Dossus L, et al., 2022, Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition, BMC Medicine, Vol: 20, ISSN: 1741-7015
BACKGROUND: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. METHODS: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. RESULTS: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. CONCLUSIONS: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Botteri E, Peveri G, Berstad P, et al., 2022, Changes in lifestyle and risk of colorectal cancer in the European prospective investigation into cancer and nutrition., American Journal of Gastroenterology, Vol: 10, Pages: 1-10, ISSN: 0002-9270
INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. METHODS: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.
Deschasaux-Tanguy M, Huybrechts I, Julia C, et al., 2022, Food choices characterized by the Nutri-Score nutrient profile and risk of cardiovascular diseases, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262
Yarmolinsky J, Robinson J, Tsilidis KK, et al., 2022, Using Human Genetics to Evaluate the Causal Role of Circulating Inflammatory Markers in Risk of Adult Cancer, Publisher: WILEY, Pages: 547-547, ISSN: 0741-0395
Meyer A, Dong C, Casagrande C, et al., 2022, Food processing and risk of Crohn’s disease and ulcerative colitis: A European Prospective Cohort Study, Clinical Gastroenterology and Hepatology, ISSN: 1542-3565
Mayen A-L, Viallon V, Botteri E, et al., 2022, A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk, European Journal of Epidemiology, Vol: 37, Pages: 915-929, ISSN: 0393-2990
BackgroundAlcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk.ObjectiveLeveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk.MethodsWithin the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases.ResultsMean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite.ConclusionsIncreasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
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