Effect of Alpha Linolenic Acid Supplementation on Serum Prostate Specific Antigen (PSA): Results from the Alpha Omega Trial
Brouwer, I.A. ; Geleijnse, J.M. ; Klaasen, V.M. ; Smit, L.A. ; Giltay, E.J. ; Goede, J. de; Heijboer, A.C. ; Kromhout, D. ; Katan, M.B. - \ 2013
PLoS ONE 8 (2013)12. - ISSN 1932-6203
n-3 fatty-acids - cancer risk - dietary-fat - metaanalysis - men - disease
Background: Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer. Methods: The Alpha Omega Trial (ClinicalTrials.govIdentifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 262 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration,4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL). Findings: Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: 20.02 to 0.22) ng/mL (P = 0.12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58). Interpretation: An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from 20.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.
Dietary supplement use is not associated with recurrence of colorectal adenomas : a prospective cohort study
Heine-Bröring, R.C. ; Winkels, R.M. ; Botma, A. ; Wahab, P.J. ; Tan, A.C.I.T.L. ; Nagengast, F.M. ; Witteman, B.J.M. ; Kampman, E. - \ 2013
International Journal of Cancer 132 (2013)3. - ISSN 0020-7136 - p. 666 - 675.
food frequency questionnaire - health interview survey - vitamin-d - united-states - life-style - folic-acid - antioxidant vitamins - relative validity - clinical-trial - cancer risk
Diet and lifestyle influence colorectal adenoma recurrence. The role of dietary supplement use in colorectal adenoma recurrence remains controversial. In this prospective cohort study, we examined the association between dietary supplement use, total colorectal adenoma recurrence and advanced adenoma recurrence. Colorectal adenoma cases (n = 565) from a former case–control study, recruited between 1995 and 2002, were prospectively followed until 2008. Adenomas with a diameter of =1 cm and/or (tubulo)villous histology and/or with high grade dysplasia and/or =3 adenomas detected at the same colonic examination were considered advanced adenomas. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary supplement users (use of any supplement during the past year) compared to nonusers and colorectal adenoma recurrence were calculated using stratified Cox proportional hazard models for counting processes and were adjusted for age, sex, educational level and number of colonoscopies during follow-up. Robust sandwich covariance estimation was used to adjust for the within subject correlation. A number of 165 out of 565 adenoma patients had at least one colorectal adenoma recurrence during a median person-time of 5.4 years and of these, 37 patients had at least one advanced adenoma. One-third of the total study population (n = 203) used a dietary supplement. Compared to no use, dietary supplement use was neither statistically significantly associated with total colorectal adenoma recurrence (HR = 1.03; 95% CI 0.79–1.34) nor with recurrent advanced adenomas (HR = 1.59; 95% CI 0.88–2.87). This prospective cohort study did not suggest an association between dietary supplement use and colorectal adenoma recurrence
Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Vogel, S. de; Schneede, J. ; Ueland, P.M. ; Vollset, S.E. ; Meyer, K. ; Fredriksen, A. ; Midttun, O. ; Bjorge, T. ; Kampman, E. ; Bretthauer, M. ; Hoff, G. - \ 2011
Cancer Epidemiology Biomarkers and Prevention 20 (2011)8. - ISSN 1055-9965 - p. 1726 - 1735.
nested case-control - methylenetetrahydrofolate reductase polymorphism - island methylator phenotype - tandem mass-spectrometry - cancer risk - plasma folate - b-vitamins - microbiological assay - genetic polymorphisms - asymptomatic adults
Background: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome. Methods: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we cross-sectionally investigated associations between distal colorectal adenoma occurrence-potential precursor lesions of colorectal carcinomas-and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism. Results: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45-0.83), betaine: OR = 0.74; 95% CI = 0.54-1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49-0.88, and the vitamin B6 form pyridoxal 5'-phosphate (PLP): OR = 0.69; 95% CI = 0.51-0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually. Conclusions: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas. Impact: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(8); 1726-35. (C)2011 AACR.
Irregularly shaped inclusion cysts display increased expression of Ki67, Fas, Fas ligand, and procaspase-3 but relatively little active caspase-3
Slot, K.A. ; Boer-Brouwer, M. de; Voorendt, M. ; Sie-Go, D.M.D.S. ; Ghahremani, M. ; Dorrington, J.H. ; Teerds, K.J. - \ 2006
International Journal of Gynecological Cancer 16 (2006)1. - ISSN 1048-891X - p. 231 - 239.
apoptosis-related proteins - human ovarian-tumors - mediated apoptosis - epithelial tumors - surface epithelium - cancer risk - cell - p53 - antigen - system
Human ovarian cancers are thought to arise from sequestered ovarian surface epithelial (OSE) cells that line the wall of inclusion cysts. Nevertheless, the early events toward neoplasia are not well understood. In this study, immunoreactivity for apoptotic proteins in human OSE of control and tumor ovarian sections was examined. Ki67, a marker for cell proliferation, was generally absent in the flat-to-cuboidal OSE cells on the ovarian surface and in regularly shaped inclusion cysts. Fas, Fas ligand, and caspase-3, components of the apoptotic pathway, were also largely absent. Ki67, Fas, Fas ligand, and procaspase-3 expression, though not active caspase-3 expression, was more frequently observed in epithelial cells lining irregularly shaped inclusion cysts, particularly in the columnar and Müllerian-like OSE cell types that resembled ovarian tumor OSE cells. Immunoreactivity for these factors as well as active caspase-3 was found frequently in ovarian tumors. We postulate that the appearance of the Fas system and its related proteins in sequestered columnar OSE cells of irregularly shaped inclusion cysts may contribute to balance cell growth with cell death, although little active caspase-3 expression was observed. Further studies are required to identify whether inhibition of apoptosis in inclusion cysts is an early event in ovarian carcinogenesis.
Human NAD(P)H:Quinone oxidoreductase inhibition by flavonoids in living cells
Lee, Y.Y. ; Westphal, A.H. ; Haan, L.H.J. de; Aarts, J.M.M.J.G. ; Rietjens, I.M.C.M. - \ 2005
Free Radical Biology and Medicine 39 (2005)2. - ISSN 0891-5849 - p. 257 - 265.
hamster ovary cells - dt-diaphorase - quinone oxidoreductase - acceptor oxidoreductase - antitumor quinones - human plasma - cancer risk - quercetin - reductase - rat
Procedures for assessing enzyme inhibition in living cells are an important tool in the study of the relevance of enzyme-catalyzed reactions and interactions in the human body. This paper presents the effects of flavonoids on NAD(P)H:quinone oxidoreductase 1 (NQO1) activity, by a newly developed method to measure NQO1 inhibition in intact cells. The principle of this method is based on the resorufin reductase activity of NQO1. The change in fluorescence in time was used to determine NQO1 activity in intact Chinese hamster ovary (CHO) cells genetically engineered to overexpress human NQO1. Applying this method to determine the inhibitory effects of reported in vitro NQO1 inhibitors (dicoumarol, 7,8-dihydroxyflavone, chrysin) showed that for all inhibitors tested, the IC50 in intact cells was at least 3 orders of magnitude higher than the IC50 in cell lysates. This result demonstrates that in vitro studies with purified NQO1 or with extracts from disrupted tissues are of limited value for obtaining insight into the situation in living cells. Possible factors underlying this discrepancy are being discussed. For the first time, we determined NQO1 inhibition by flavonoids in cells without disruption of the cells or addition of cofactors, enabling the assessment of enzymatic activity and the interaction of modulators of enzymatic activity in an intracellular situation.
Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas
Tiemersma, E.W. ; Bunschoten, J.E. ; Kok, F.J. ; Glatt, H. ; Boer, S.Y. van; Kampman, E. - \ 2004
International Journal of Cancer 108 (2004)1. - ISSN 0020-7136 - p. 97 - 103.
microsomal epoxide hydrolase - s-transferase m1 - alcohol-consumption - risk-factors - cancer risk - metabolic-activation - gstt1 polymorphisms - allele frequencies - tobacco smoking - null genotype
Cigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case-control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N-acetyltransferases (NAT1 and NAT2) and glutathione S-transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp-free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction-restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% CI = 1.4-4.1) compared to never smoking. Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association
Risk of colorectal adenomas in relation to meat consumption, meat preparation, and genetic susceptibility in a Dutch population
Tiemersma, E.W. ; Voskuil, D.W. ; Bunschoten, A. ; Kok, F.J. ; Kampman, E. - \ 2004
Cancer Causes and Control 15 (2004)3. - ISSN 0957-5243 - p. 225 - 236.
heterocyclic aromatic-amines - cancer risk - polyadenylation polymorphism - acetyltransferase-1 gene - metabolic-activation - varying degrees - united-states - pan residues - well-done - nat1
Objective: We studied the association between meat consumption and colorectal adenomas, and potential influence of genetic susceptibility to heterocyclic aromatic amines (HCAs) formed during meat cooking at high temperatures. Methods: We studied HCA concentration in relation to preparation habits among 63 volunteers. Associations of meat consumption, meat preparation habits, and genetic susceptibility with colorectal adenoma risk were investigated among 431 adenoma cases and 433 polyp-free controls recruited at endoscopy. Participants completed a meat consumption and preparation questionnaire and provided blood for DNA isolation. Polymorphisms of N-acetyltransferases (NAT) 1 and 2, sulfotransferase (SULT) 1A1, and glutathione-S-transferases (GST) M1 and T1 were determined. Results: HCAs were present in habitually prepared meat, although meat consumption (7 versus <5x/week) did not increase the risk of colorectal adenomas (odds ratio (OR) 1.2, 95% confidence interval (CI) 0.8 - 1.9). Also, presumed unfavorable preparation habits (e.g., use of lid, preference for darkly browned meat) did not increase adenoma risk (OR 0.8 and 0.9, respectively). Only the combination of NAT2 slow acetylation and frequent meat consumption (> 5x/week) slightly increased adenoma risk (OR 1.6, 95% CI 1.1 - 2.3). Conclusions: In this Dutch population, unfavorable meat consumption and preparation habits did not increase colorectal adenoma risk, and these associations were not influenced by relevant genetic polymorphisms.
Meat consumption and meat preparation in relation to colorectal adenomas among sporadic and HNPCC family patients in The Netherlands
Voskuil, D.W. ; Kampman, E. ; Grubben, M.J.A.L. ; Kok, F.J. ; Nagengast, F.M. ; Vasen, H.F.A. ; Veer, P. van 't - \ 2002
European Journal of Cancer 38 (2002)17. - ISSN 0959-8049 - p. 2300 - 2308.
heterocyclic amines - tumor spectrum - cancer risk - k-ras - mutations - diet - tumorigenesis - polyposis - history
Meat consumption and meat preparation methods are thought to be associated with the risk of sporadic colorectal cancer, and possibly adenomas. As the same somatic mutations occur in sporadic adenomas and hereditary non-polyposis colorectal cancer (HNPCC)-related adenomas, similar exogenous factors may play a role in the development of both types of adenoma. In a case control study among 57 sporadic colorectal adenoma cases and 62 adenoma cases from HNPCC families (and 148 adenoma-free controls) from the Netherlands, we examined whether meat consumption and preparation are similarly associated with sporadic and suspected HNPCC colorectal adenomas. Frequency of meat consumption was not significantly associated with adenoma risk in our population of sporadic and HNPCC family cases and controls (Odds Ratios (OR) for high versus low consumption were 1.0 and 0.6, respectively). Interestingly, consumption of red meat and specific preparation methods (i.e., “not adding any water” and “ closed lid with most meat types”) slightly, but non-significantly, increased the risk of adenomas in the sporadic group only (OR, 95% Confidence Interval (CI): 4.1, 0.7–23.0, 2.0, 0.6–6.5 and 2.6, 0.9–7.2, respectively). This is the first study to examine possible differences or similarities in risk factors for sporadic and HNPCC colorectal carcinogenesis. Our results do not provide support for meat consumption as a risk factor for adenoma formation in HNPCC family members. Some characteristics of habitual meat preparation in the Netherlands may, however, increase the risk of sporadic adenomas.