Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) ...is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-). VDR null mice do not develop GI or extra-colonic tumors but loss of VDR decreased intestinal tumor latency and increased progression to adenocarcinoma in both models. AOM treatment of VDR null mice also caused squamous cell carcinoma of the anus. Although levels and distribution of total or activated β-catenin in the epithelial component of tumors were unaffected by loss of VDR, β-catenin dependent cyclin D1 expression was affected suggesting a direct VDR effect on β-catenin co-activator activity. Extra-colonic mucosa manifestations in Apc1638N/+Vdr-/- animals included increased nuclear β-catenin in submucosal stromal cells, spleno- and cardiomegaly and large epidermoid cysts characteristic of the FAP variant, Gardner's syndrome. Consistent with this, SNPs in the VDR, vitamin D binding protein and CYP24 as well as mutations in APC distal to codon 850 were strongly associated with Gardners syndrome in a cohort of 457 FAP patients, This work suggests that alterations in the vitamin D/VDR axis are important in Gardner's syndrome, as well as in the etiology of anal cancer.
Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer.
We conducted a nested case-control study within the ...European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk.
Tryptophan (Ptrend = 2 × 10(-5)) and the kynurenine/tryptophan ratio (KTR; Ptrend = 4 × 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th vs. 1st) were 0.52 95% confidence interval (CI), 0.37-0.74 for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR (Ptrend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, Ptrend = 3 × 10(-5)) that was only marginally affected by adjusting for methionine.
This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology.
This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and ...dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case–control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α‐ and β‐carotene, canthaxanthin, β‐cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α‐, β‐ and γ‐ and δ‐tocopherol) and dietary consumption of β‐carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary β‐carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.
What's New?
Carotenoids and vitamins A, C, and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption with the risk of CRC was examined in this largest case‐control study. Higher levels of plasma retinol (vitamin A)‐‐which exerts diverse cellular activities‐‐were associated with a 40% lower risk of colon cancer and a 55% lower risk of proximal cancer. There was little evidence, however, for a role of vitamins and carotenoids with antioxidative properties. The role of retinol in the etiology of colon cancer should be further investigated.
Purpose
We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced ...by characteristics of individuals or centers.
Methods
The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (
n
= 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables.
Results
For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (
p
< 0.01 in all analyses). In addition, mode of administration (
p
= 0.06 in women) and day of the week (
p
= 0.03 in men and
p
= 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results.
Conclusion
The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across centers.
Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so ...far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow‐up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83–0.99; p‐trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86–1.02; p‐trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (pheterogeneity<0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear.
What's new?
The role of diet in prostate‐cancer etiology is uncertain, and associations may vary by tumor characteristics. In this prospective, longitudinal study, the authors examined the association of total and subtypes of fruit and vegetable intake with the overall incidence of prostate cancer. They then analyzed incidence by grade, stage of disease, and prostate‐cancer death. They found that higher fruit intake was associated with a small reduction in prostate cancer risk, and that this association did not differ by tumor characteristics.
The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade ...of the disease. The association between self‐reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow‐up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC‐participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross‐sectional association between circulating concentrations of androgens and insulin‐like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63–0.86). There was no evidence that the association differed by stage (p‐heterogeneity, 0.19) or grade (p‐heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin‐like growth factor binding protein‐three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self‐reported diabetes mellitus and subsequent risk of prostate cancer.
What's new?
Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin‐like growth factor binding protein‐three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.
In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7(th) most common type of cancer. Although many previous studies focused on the relationship between diet and ...bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage.
The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case-control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer.
The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer.
Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to ...changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.
To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.
Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.
Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.
Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval CI 0.69–0.86; p<0.001) compared with men with higher concentrations (2nd–10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67–0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95–2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.
Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.
In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.
We found that men with low circulating free testosterone had a 23% reduced risk of overall prostate cancer, but there was some evidence that these men had an increased risk of developing high-grade disease.
High dairy protein intake has been found to be associated with increased prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). To further examine this ...possible relationship, we investigated the hypothesis that a genetic polymorphism in the lactase (LCT) gene might be associated with elevated dairy product intake and increased prostate cancer risk in a case–control study nested in EPIC. The C/T‐13910 lactase variant (rs4988235) was genotyped in 630 men with prostate cancer and 873 matched control participants. Dairy product consumption was assessed by diet questionnaire. Odds ratios (ORs) for prostate cancer in relation to lactase genotype were estimated by conditional logistic regression. Lactase genotype frequency varied significantly between countries, with frequencies of the T (lactase persistence) allele ranging from 7% in Greece to 79% in Denmark. Intake of milk and total dairy products varied significantly by lactase genotype after adjustment for recruitment center; adjusted mean intakes of milk were 44.4, 69.8 and 82.3 g/day among men with CC, CT and TT genotypes, respectively. The lactase variant was not significantly associated with prostate cancer risk, both in our data (adjusted OR for TT vs. CC homozygotes: 1.10, 95% CI: 0.76–1.59) and in a meta‐analysis of all the published data (combined OR for T allele carriers vs. CC homozygotes: 1.12, 0.96–1.32). These findings show that while variation in the lactase gene is associated with milk intake in men, the lactase polymorphism does not have a large effect on prostate cancer risk.
What's new?
High dairy protein intake has previously been found to be associated with increased prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). The current study was nested in EPIC, and results from this first Europe‐wide study suggest that while the C/T13910 lactase polymorphism is associated with milk intake, the variant has no large effect on prostate cancer risk. The data illustrate the challenges of applying mendelian randomisation to explore the relationship between dairy product consumption and cancer risk. Very large studies with both genetic and dietary data are thus needed for investigations using genetic proxies of nutritional exposures.
The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with ...prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center‐specific validated dietary questionnaires at baseline and calibrated with 24‐h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow‐up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (pheterogeneity < 0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD = 1.08; 95%CI = 1.01–1.15; p‐trend = 0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n‐9c; HR1SD = 1.05; 1.00–1.11; p‐trend = 0.048) and eicosapentaenoic acid (20:5n‐3c; HR1SD = 1.07; 1.00–1.14; p‐trend = 0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk.
What's new?
Are individual dietary fatty acids associated with prostate cancer development and progression? In this large, prospective study, the authors found that for prostate cancer overall, the answer is no. However, a higher intake of butyric acid may be associated with an increased risk of advanced‐stage prostate cancer, and higher intakes of eicosenoic and eicosapentaenoic acids may be positively associated with risk of lethal prostate cancer.
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