Scope
The goal of this work is to identify circulating biomarkers of habitual coffee intake using a metabolomic approach, and to investigate their associations with coffee intake in four European ...countries.
Methods and results
Untargeted mass spectrometry‐based metabolic profiling is performed on serum samples from 451 participants of the European Prospective Investigation on Cancer and Nutrition (EPIC) originating from France, Germany, Greece, and Italy. Eleven coffee metabolites are found to be associated with self‐reported habitual coffee intake, including eight more strongly correlated (r = 0.25–0.51, p < 10E−07). Trigonelline shows the highest correlation, followed by caffeine, two caffeine metabolites (paraxanthine and 5‐Acetylamino‐6‐amino‐3‐methyluracil), quinic acid, and three compounds derived from coffee roasting (cyclo(prolyl‐valyl), cyclo(isoleucyl‐prolyl), cyclo(leucyl‐prolyl), and pyrocatechol sulfate). Differences in the magnitude of correlations are observed between countries, with trigonelline most highly correlated with coffee intake in France and Germany, quinic acid in Greece, and cyclo(isoleucyl‐prolyl) in Italy.
Conclusion
Several biomarkers of habitual coffee intake are identified. No unique biomarker is found to be optimal for all tested populations. Instead, optimal biomarkers are shown to depend on the population and on the type of coffee consumed. These biomarkers should help to further explore the role of coffee in disease risk.
Eleven metabolites measured in serum samples from 451 subjects of the European Prospective Investigation on Cancer and Nutrition (EPIC) study originating from France, Germany, Greece and Italy were found to be associated with coffee intake. They include trigonellline, caffeine and caffeine metabolites, quinic acid, and two diketopiperazines and catechol sulfate derived from coffee roasting. Variations in the magnitude of correlations and of ratios between metabolites indicate differences in the composition of coffee brews consumed by individuals from the four countries.
Many studies have demonstrated that lifestyle factors, including diet, may influence cancer survival. The number of cancer survivors is increasing worldwide and little is known about long‐term diet ...changes in people who had cancer. We studied 53,981 women from the prospective E3N‐EPIC cohort study with available dietary data in 1993 and 2005, among whom 4,619 had a cancer diagnosis inbetween (including n = 2,699 breast cancers). We evaluated the potential impact of a cancer diagnosis (comparing women with cancer to women with no cancer) on changes in FV consumption using multivariable linear regression models considering cancer site, stage at diagnosis and socioeconomic factors. Compared to women with no cancer, a statistically significant increase in FV consumption (β=+2.65%, 1.22–4.09) was observed in women who had cancer, and this association appeared to be driven by breast cancer exclusively. The increase in FV consumption was larger in women who had an advanced stage of breast cancer (stages II–IV) (β=+7.23%, 3.92–10.5) than in women with stages 0–I (β=+2.03%, −0.20 to 4.26). Women with no partner and no children were those having the highest increase in FV consumption (β=+18.71%, 6.51–30.91). These changes were only observed in specific SE groups. When considering adherence to guidelines, the proportion of women who consumed less than 7.5 portions a day in 1993 and more in 2005 was greater in women with advanced breast cancer. More research is now needed to understand how the inequities we observed impact the long‐term health after cancer.
What's new?
Eat a diet rich in fruits and vegetables, doctors say, to prevent cancer. But will eating more fruits and vegetables after diagnosis improve the chances of survival? Here, the authors looked at dietary data from women in the EPIC cohort study, over a 12‐year period, to see whether a cancer diagnosis would spur women to change their diet. Women diagnosed with advanced breast cancer, they found, significantly increased their fruit and vegetable consumption, compared with women who were not diagnosed. The improvements in diet, however, were seen only in women in certain socioeconomic groups.
Scope
Processed meat intake has been associated with adverse health outcomes. However, little is known about the type of processed meat more particularly responsible for these effects. This study ...aims to identify novel biomarkers for processed meat intake.
Methods and Results
In a controlled randomized cross‐over dietary intervention study, 12 healthy volunteers consume different processed and non‐processed meats for 3 consecutive days each. Metabolomics analyses are applied on post‐intervention fasting blood and urine samples to identify discriminating molecular features of processed meat intake. Nine and five pepper alkaloid metabolites, including piperine, are identified as major discriminants of salami intake in urine and plasma, respectively. The associations with processed meat intake are tested for replication in a cross‐sectional study (n = 418) embedded within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Three of the serum metabolites including piperine are associated with habitual intake of sausages and to a lesser extent of total processed meat.
Conclusion
Pepper alkaloids are major discriminants of intake for sausages that contain high levels of pepper used as ingredient. Further work is needed to assess if pepper alkaloids in combination with other metabolites may serve as biomarkers of processed meat intake.
In a dietary intervention study, nine and five pepper alkaloid metabolites are identified as major discriminants of salami intake compared to non‐processed pork, in urine and plasma, respectively. Three of the blood metabolites including piperine are associated with sausage intake in a cross‐sectional study. Pepper alkaloids are important discriminants of processed meat intake and sausage is a major food source.
Experimental studies have shown a protective effect of nonsteroidal anti‐inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less ...consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self‐reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard ratios for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow‐up time period of 13 years, 7,379 incident breast cancer cases were diagnosed (816 in situ and 6,563 invasive). There were no statistically significant associations between NSAID use and breast cancer risk, overall and by subtypes. However, a statistically significant interaction was observed for invasive cases between NSAID use and ever use of menopausal hormonal therapy (MHT) among postmenopausal women MHT users: HRNSAID use = 0.84 (0.73–0.96); non MHT users: HRNSAID use = 1.08 (0.93–1.25); pinteraction = 0.05. Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in‐depth investigation in studies with accurate data on both NSAID and MHT use.
What's new?
Chronic inflammation is a suspected factor in breast cancer development. Hence, the possibility of stemming tumorigenic inflammatory effects with nonsteroidal anti‐inflammatory drugs (NSAIDs) has drawn significant interest. Here, using data from the European Prospective Investigation into Cancer and Nutrition prospective cohort study, the authors reveal an association between NSAID use and decreased risk of invasive breast cancer specifically in postmenopausal women who ever used menopausal hormonal therapy (MHT). No association was found between NSAID use and breast cancer risk in non‐MHT users. Additional investigation is needed to better understand interactions between MHT use, NSAIDs, and breast cancer risk.
This study aimed to evaluate the association between thyroid dysfunction and breast cancer risk. We included 239,436 females of the UK Biobank cohort. Information on thyroid dysfunction, personal and ...family medical history, medications, reproductive factors, lifestyle, and socioeconomic characteristics was retrieved from baseline self‐reported data and hospital inpatient databases. Breast cancer diagnoses were identified through population‐based registries. We computed Cox models to estimate hazard ratios (HRs) of breast cancer incidence for thyroid dysfunction diagnosis and treatments, and examined potential confounding and effect modification by comorbidities and breast cancer risk factors. In our study, 3,227 (1.3%) and 20,762 (8.7%) women had hyper‐ and hypothyroidism prior to the baseline. During a median follow‐up of 7.1 years, 5,326 (2.2%) women developed breast cancer. Compared to no thyroid dysfunction, there was no association between hypothyroidism and breast cancer risk overall (HR = 0.93, 95% confidence interval (CI): 0.84–1.02, 442 cases), but we found a decreased risk more than 10 years after hypothyroidism diagnosis (HR=0.85, 95%CI 0.74–0.97, 226 cases). There was no association with hyperthyroidism overall (HR=1.08, 95%CI 0.86–1.35, 79 cases) but breast cancer risk was elevated among women with treated hyperthyroidism (HR=1.38, 95%CI: 1.03–1.86, 44 cases) or aged 60 years or more at hyperthyroidism diagnosis (HR=1.74, 95%CI: 1.01–3.00, 113 cases), and 5–10 years after hyperthyroidism diagnosis (HR=1.58, 95%CI: 1.06–2.33, 25 cases). In conclusion, breast cancer risk was reduced long after hypothyroidism diagnosis, but increased among women with treated hyperthyroidism. Future studies are needed to determine whether the higher breast cancer risk observed among treated hyperthyroidism could be explained by hyperthyroidism severity, type of treatment or aetiology.
In this study, we included 239,436 women in the general population‐based UK Biobank cohort to investigate the association between thyroid dysfunction and breast cancer risk. Our study suggested there was no association between hyper‐ and hypothyroidism in overall and breast cancer risk. However, among treated hyperthyroidism, we found a higher breast cancer risk, which could be explained by hyperthyroidism severity or aetiology.
Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut ...intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country‐specific dietary questionnaires. After a mean follow‐up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72–1.10; p‐trend = 0.70). Furthermore, no evidence for effect‐measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.
What's new?
Environmental and lifestyle factors probably play a major role in the development—or prevention—of pancreatic cancer (PC). For example, might the inclusion of nuts in one's diet reduce the risk of PC? Results of previous studies have been contradictory. In this analysis of data from the large, prospective EPIC study, the authors found no significant protective role for nuts or seeds against PC.
Although adult obesity has been associated with poor breast cancer survival, data on adiposity at different periods in life and its lifelong evolution are scarce. Our aims were to assess the ...associations between breast cancer survival and body size during childhood, puberty and early adulthood and body size trajectories from childhood to adulthood. Self‐assessed body size at age 8, at puberty, at age 20–25 and at age 35–40 and trajectories of body size of 4,662 breast cancer survivors from the prospective E3N cohort were studied in relation to risk of death from any cause, death from breast cancer and second invasive cancer event using multivariate Cox regression models. Four trajectories of body size were identified (T1 “moderate increase,” T2 “stable/low increase,” T3 “increase at puberty” and T4 “constantly high”). Compared with stable body size, an increase in body size during adult life was associated with an increased risk of death from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01–1.60) and an increased risk of second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06–1.47). Silhouettes at various ages were not associated with survival. Our results suggest that the evolution of body size from childhood to adulthood has a long‐term influence on breast cancer survival. Although these results need to be confirmed, this work sheds light on the need to combine lifelong approaches to current BMI to better identify breast cancer survivors who are at higher risk of recurrence or second primary cancer, or of death.
What's new?
Obesity is a known factor affecting breast cancer survival. It remains unclear, however, whether body size in early life is associated with breast cancer survival in adulthood, or whether only adult obesity is relevant in this context. Here, analyses of life‐course body size from childhood through puberty to adulthood show that an increase in body silhouette, particularly during adulthood, is associated with elevated risks of breast cancer recurrence, second primary cancer and death. The findings suggest that consideration of body size trajectory can help identify breast cancer survivors with increased likelihood of recurrence and poor outcome.
Immuno‐proteomic screening has identified several tumor‐associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and ...cancer‐testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo‐luminiscence. Diagnostic discrimination statistics were calculated by strata of lead‐time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 95% CI 0.08–0.40 for CTAG1A, CTAG2 and NUDT1 to 0.23 0.10–0.44 for P53 (0.33 0.11–0.68 for high‐grade serous tumors). However, at longer lead‐times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01–0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
What's new?
Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected.
Aims/hypothesis
Recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes. The diet, and especially fruit and vegetables, contains a variety of compounds ...with antioxidant activity, which may have cumulative/synergistic antioxidant effects. The total antioxidant capacity, an index derived from dietary intake, is a single estimate of antioxidant capacity from all dietary antioxidants. The main aim of this study was to investigate the relationship between total antioxidant capacity and risk of type 2 diabetes.
Methods
Among 64,223 women (mean age 52 ± 7 years) from the French E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1751 women had validated type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders.
Results
In multivariable models, higher levels of total antioxidant capacity were associated with a lower risk of type 2 diabetes. Compared with women in the lowest quintile, women in the third, fourth and fifth quintiles for total antioxidant capacity had HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and risk of type 2 diabetes was linear up to values of 15 mmol/day, after which the effect reached a plateau.
Conclusions/interpretation
Our findings suggest that the total antioxidant capacity may play an important role in reducing the risk of type 2 diabetes in middle-aged women. More studies are warranted to better understand the biological mechanisms underlying this inverse association.
In addition to tumor characteristics and lifestyle factors, cancer relapses are often related to the risk of death but have not been jointly studied. We investigate the prognostic factors of ...recurrent events and death after a diagnosis of breast cancer and predict individual deaths including a history of recurrences.
The E3N (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale) study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. Overall survival and three types of recurrent events were considered: locoregional recurrence, metastasis, and second primary breast cancer. Recurrent events and death were analyzed using a joint frailty model.
The analysis included 4926 women from the E3N cohort diagnosed with a first primary invasive breast cancer between June 1990 and June 2008; during the follow-up, 1334 cases had a recurrence (median time of follow-up is 7.2 years) and 469 women died. Cases with high grade, large tumor size, axillary nodal involvement, and negative estrogen and progesterone receptors had a higher risk of recurrence or death. Furthermore, smoking increased the risk of relapse. For cases with a medium risk profile in terms of tumor characteristics and lifestyle factors, the probability of dying between 5 and 10 years after diagnosis was 6, 20 and 36% for 0, 1 or 2 recurrences within the first 5 years after diagnosis, respectively.
Our study showed the importance of considering baseline lifestyle characteristics and history of relapses to dynamically predict the risk of death in breast cancer cases. Medical experience coupled with an estimate of a patient's survival probability that considers all available information for this patient would enable physicians to make better informed decisions regarding their actions and thus improve clinical output.
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