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

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

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

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

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients:results from the ColoCare Study

B-vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- A nd angiogenesis-related chronic diseases, such as colorectal cancer. Yet, the role of one-carbon metabolism in inflammation and angiogenesis among colorectal cancer patients remains unclear.The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed colorectal cancer patients (n=238) in the prospective ColoCare Study, Heidelberg.We cross-sectionally analyzed associations between 12 B-vitamins and one-carbon metabolites and 10 inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesized that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers.We observed that PLP was inversely associated with CRP (r=-0.33, plinearlinear=0.003), IL-6 (r=-0.39, plinear linear=0.02) and TNFα (r=-0.12, plinear=0.045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r=-0.14), SAA (r=-0.14) and TNFα (r=-0.15) among colorectal cancer patients. Folate catabolite apABG was positively correlated with IL-6 (r= 0.27, plinearlinear<0.0001), indicating higher folate utilization during inflammation.Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among colorectal cancer patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for colorectal cancer patients.</p

Increases in adipose tissue and muscle function are longitudinally associated with better quality of life in colorectal cancer survivors

Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I-III CRC survivors (n=459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.Trial registration: NTR7099

Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk - results from the EPIC cohort study

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7-±-8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk

Prediagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort

Background: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). Methods: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH) D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk. Results: In multivariate analyses [including adjustment for 25(OH) D concentration] with a priori defined cutoff points, high levels of serum PTH (&gt;= 65 ng/L) compared with medium PTH levels of 30-65 ng/L were associated with increased CRC risk (RR = 1.41,95% CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14-2.75) and 1.15 (95% CI: 0.73-1.84) in men and women, respectively (P-heterogeneity = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03-2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72-2.01 (P-heterogeneity = 0.21). Effect modification by various risk factors was examined. Conclusions: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. Impact: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. Cancer Epidemiol Biomarkers Prev; 20(5); 767-78. (C)2011 AACR

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-TrOndelag Health Study’s second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D-2 and 25(OH)D-3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of &gt;50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of 25; &gt;25 to 50; &gt;75 to 100; and &gt;100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant

Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: A nested case-control study

Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case-control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4-Q1 [95% CI]: 1.07 [0.85-1.36], p(trend) = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4-Q1 [95% CI]: 0.97 [0.67-1.38], p(trend) = 0.90) and estrogen receptor negative tumors (ORQ4-Q1 [95% CI]: 0.97 [0.66-1.42], p(trend) = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80-1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) <25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI 25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer. What's new? Experimental studies have indicated that vitamin D may play a role in preventing tumor formation in the breast. However, in the present investigation, the largest prospective case-control study on circulating 25-hydroxyvitamin D (25(OH)D) and breast cancer risk conducted to date, pre-diagnostic levels of 25(OH)D were found to be unrelated to overall breast cancer risk. While the results support those of similar prospective studies, a significant inverse association was detected between 25(OH)D levels and incident breast cancer in women taking hormone replacement therapy, suggesting that background factors may influence risk associations

Adiposity, mediating biomarkers and risk of colon cancer in the European Prospective Investigation into Cancer and Nutrition Study

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; p(trend)=0.02) and in women (RR 1.67, 95% CI 1.09-2.56; p(trend)=0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk. What’s new? Adiposity is a well-established risk factor for colon cancer. However, the mechanisms that underlie this relationship still aren’t well understood. In this study, the authors evaluated a panel of inflammatory and metabolic biomarkers for their impact on colon-cancer risk. They found that serum levels of high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin, and soluble leptin receptor had the greatest impact on the association between adiposity and colon cancer. These biomarkers may thus lead to promising strategies for the targeted prevention of colon cancer