-
1.
Effects of 2-Phenethyl Isothiocyanate on Metabolism of 1,3-Butadiene in Smokers.
Boldry, EJ, Yuan, JM, Carmella, SG, Wang, R, Tessier, K, Hatsukami, DK, Hecht, SS, Tretyakova, NY
Cancer prevention research (Philadelphia, Pa.). 2020;(1):91-100
-
-
Free full text
-
Abstract
2-Phenethyl isothiocyanate (PEITC) is a natural product found as a conjugate in cruciferous vegetables. It has been reported to have preventative properties against lung cancer and to inhibit metabolic activation of tobacco carcinogens. In this study, we evaluated the ability of PEITC to influence the metabolism of the human carcinogen 1,3-butadiene in current smokers in a phase II clinical trial with a crossover design. Urinary mercapturic acids of 1,3-butadiene were quantified at baseline and during PEITC treatment. Seventy-nine smokers were randomly assigned to one of two arms: PEITC followed by placebo or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. Oral ingestion of PEITC increased urinary levels of BD-mercapturic acids (MHBMA and DHBMA) by 11.1% and 3.7%, respectively, but these increases were not statistically significant (P = 0.17 and 0.64, respectively). A much stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals, PEITC increased urinary levels of MHBMA by 58.7% (P = 0.004) and 90.0% (P = 0.001), respectively, but did not have a significant effect on urinary DHBMA. These results reveal a potentially protective effect of PEITC treatment with respect to the detoxification of 1,3-butadiene in cigarette smokers, specifically in those null for GSTT1, and provide further evidence in support of stronger chemopreventive effects from consumption of dietary isothiocyanates in these individuals.
-
2.
Effects of genistein supplementation on genome‑wide DNA methylation and gene expression in patients with localized prostate cancer.
Bilir, B, Sharma, NV, Lee, J, Hammarstrom, B, Svindland, A, Kucuk, O, Moreno, CS
International journal of oncology. 2017;(1):223-234
-
-
Free full text
-
Abstract
Epidemiological studies have shown that dietary compounds have significant effects on prostate carcinogenesis. Among dietary agents, genistein, the major isoflavone in soybean, is of particular interest because high consumption of soy products has been associated with a low incidence of prostate cancer, suggesting a preventive role of genistein in prostate cancer. In spite of numerous studies to understand the effects of genistein on prostate cancer, the mechanisms of action have not been fully elucidated. We investigated the differences in methylation and gene expression levels of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy using Illumina HumanMethylation450 and Illumina HumanHT-12 v4 Expression BeadChip Microarrays. The present study was a randomized, placebo-controlled, double-blind clinical trial on Norwegian patients who received 30 mg genistein or placebo capsules daily for 3-6 weeks before prostatectomy. Gene expression changes were validated by quantitative PCR (qPCR). Whole genome methylation and expression profiling identified differentially methylated sites and expressed genes between placebo and genistein groups. Differentially regulated genes were involved in developmental processes, stem cell markers, proliferation and transcriptional regulation. Enrichment analysis suggested overall reduction in MYC activity and increased PTEN activity in genistein-treated patients. These findings highlight the effects of genistein on global changes in gene expression in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
-
3.
Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas: A Randomized Clinical Trial.
Barry, EL, Peacock, JL, Rees, JR, Bostick, RM, Robertson, DJ, Bresalier, RS, Baron, JA
JAMA oncology. 2017;(5):628-635
-
-
Free full text
-
Abstract
IMPORTANCE Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial. OBJECTIVE To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. DESIGN, SETTING, AND PARTICIPANTS We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study's treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016. INTERVENTIONS Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. MAIN OUTCOMES AND MEASURES The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing. RESULTS Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D' = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation. CONCLUSIONS AND RELEVANCE Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153816.
-
4.
Supplementation with Brazil nuts and green tea extract regulates targeted biomarkers related to colorectal cancer risk in humans.
Hu, Y, McIntosh, GH, Le Leu, RK, Somashekar, R, Meng, XQ, Gopalsamy, G, Bambaca, L, McKinnon, RA, Young, GP
The British journal of nutrition. 2016;(11):1901-1911
Abstract
Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers. In total, thirty-two volunteers (>50 years of age) with plasma Se≤1·36 µmol/l were randomised to one of three treatment groups: nine to Se (approximately 48 µg/d) as six Brazil nuts, eleven to four GTE capsules (800 mg (-)-epigallocatechin-3-gallate) and twelve to a combination of Brazil nuts and GTE. Blood and rectal biopsies were obtained before and after each intervention. Plasma Se levels, rectal selenoprotein P (SePP) and β-catenin mRNA increased significantly in subjects consuming Brazil nuts alone or in combination, whereas rectal DNA methyltransferase (DNMT1) and NF-κB mRNA were reduced significantly in subjects consuming GTE alone or in combination. None of the interventions significantly affected rectal acetylated histone H3 or Ki-67 expression at the protein level or plasma C-reactive protein. Effects of the combination of Brazil nuts and GTE did not differ from what would be expected from either agent alone. In conclusion, supplementation of Brazil nuts and/or GTE regulates targeted biomarkers related to CRC oncogenesis, specifically genes associated with selenoproteins (SePP), WNT signalling (β-catenin), inflammation (NF-κB) and methylation (DNMT1). Their combination does not appear to provide additional effects compared with either agent alone.
-
5.
A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients.
Chen, AC, Martin, AJ, Dalziell, RA, McKenzie, CA, Lowe, PM, Eris, JM, Scolyer, RA, Dhillon, HM, Vardy, JL, Bielski, VA, et al
The British journal of dermatology. 2016;(5):1073-1075
-
6.
Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: a randomized controlled trial.
Tu, H, Flanders, WD, Ahearn, TU, Daniel, CR, Gonzalez-Feliciano, AG, Long, Q, Rutherford, RE, Bostick, RM
Molecular carcinogenesis. 2015;(4):270-80
-
-
Free full text
-
Abstract
Transforming growth factor alpha (TGFα) and TGFβ1 are growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively, that may (1) affect risk for colorectal cancer and (2) be modifiable by anti-proliferative exposures. The effects of supplemental calcium and vitamin D3 on these two markers in the normal-appearing colorectal mucosa in humans are unknown. We conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92; 23/treatment group) of calcium 2 g and/or vitamin D3 800 IU/d versus placebo over 6 mo. TGFα and TGFβ1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-mo follow-up. In the calcium, vitamin D3 , and calcium plus vitamin D3 groups relative to the placebo group (1) the mean overall expression of TGFβ1 increased by 14% (P= 0.25), 19% (P = 0.17), and 22% (P = 0.09); (2) the ratio of TGFα expression in the upper 40% (differentiation zone) to that in the lower 60 (proliferation zone) of the crypts decreased by 34% (P = 0.11), 31% (P = 0.22), and 26% (P = 0.33); and (3) the TGFα/TGFβ1 ratio in the upper 40% of the crypts decreased by 28% (P = 0.09), 14% (P = 0.41), and 22% (P = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and vitamin D3 may increase TGFβ1 expression and shift TGFα expression downward from the differentiation to the proliferation zone in the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation in a larger clinical trial.
-
7.
Baseline comorbidities in a skin cancer prevention trial in Bangladesh.
Argos, M, Rahman, M, Parvez, F, Dignam, J, Islam, T, Quasem, I, K Hore, S, T Haider, A, Hossain, Z, I Patwary, T, et al
European journal of clinical investigation. 2013;(6):579-88
-
-
Free full text
-
Abstract
BACKGROUND Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest that antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods and baseline analyses from the Bangladesh Vitamin E and Selenium Trial (BEST), a population-based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. MATERIALS AND METHODS Bangladesh Vitamin E and Selenium Trial is a 2 × 2 full factorial, double-blind, randomized controlled trial of 7000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of nonmelanoma skin cancer. RESULTS In cross-sectional analyses, we observed significant associations of skin lesion severity with male gender (female prevalence odds ratio (POR) = 0.87; 95% CI = 0.79-0.96), older age (aged 36-45 years, POR = 1.27; 95% CI = 1.13-1.42; aged 46-55 years, POR = 1.44; 95% CI = 1.27-1.64 and aged 56-65 years, POR = 1.50; 95% CI = 1.26-1.78 compared with aged 25-35 years), hypertension (POR = 1.29; 95% CI = 1.08-1.55), diabetes (POR = 2.13; 95% CI = 1.32-3.46), asthma (POR = 1.55; 95% CI = 1.03-2.32) and peptic ulcer disease (POR = 1.20; 95% CI = 1.07-1.35). CONCLUSIONS We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond.
-
8.
Diet adherence dynamics and physiological responses to a tomato product whole-food intervention in African-American men.
Park, E, Stacewicz-Sapuntzakis, M, Sharifi, R, Wu, Z, Freeman, VL, Bowen, PE
The British journal of nutrition. 2013;(12):2219-30
Abstract
Tomatoes may have beneficial effects on prostate health. Efficacy trials would require long-term adherence to high levels of tomato product (TP) consumption. Therefore, factors that affect adherence in men most at risk and whether increased consumption of TP negatively affects diet and health are important concerns. Cancer-free African–American (AA) men (n 36) with mean serum prostate-specific antigen of 7.4 SD 5.6) ng/ml were randomised to consume one serving of TP/d or a control diet for 3 months. Mean intervention group lycopene intake rose to 464%, with negligible control group increase. Plasma lycopene levels rose by 53 and 40% in the intervention group in months 1 and 3, respectively (P < 0.0001), with no control group change. The intervention group’s barriers to adherence score was inversely associated with both dietary (r -0.49, P = 0.02) and plasma lycopene concentration (r -0.37, P = 0.02). Their TP disadvantage score negatively correlated with the 3-month plasma lycopene concentrations (r -0.37, P = 0.008) and their weekly incentives and impediments were remarkably stable, ‘concern for prostate health’ being the most consistent over time. ‘Liking tomatoes’ and ‘study participation’ decreased in citation frequency at weeks 6 and 9, respectively. No major shifts occurred in dietary cholesterol or saturated fat, with no adverse effects on gastrointestinal complaints, serum total cholesterol, body weight or blood pressure. Lower socio-economic status AA men at higher prostate cancer risk can successfully achieve a whole food intervention goal with a corresponding rise in plasma lycopene concentrations, with no adverse effects on self-selected diet quality or health parameters.
-
9.
Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer.
Henning, SM, Wang, P, Abgaryan, N, Vicinanza, R, de Oliveira, DM, Zhang, Y, Lee, RP, Carpenter, CL, Aronson, WJ, Heber, D
Molecular nutrition & food research. 2013;(3):483-93
-
-
Free full text
-
Abstract
SCOPE Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid, and polyhydroxyphenyl-γ-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (-)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity were determined in HCT-116 colon cancer cells. METHODS AND RESULTS The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA), and polyhydroxy-γ-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. CONCLUSION The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids.
-
10.
Modulation of the association between plasma intercellular adhesion molecule-1 and cancer risk by n-3 PUFA intake: a nested case-control study.
Touvier, M, Kesse-Guyot, E, Andreeva, VA, Fezeu, L, Charnaux, N, Sutton, A, Druesne-Pecollo, N, Hercberg, S, Galan, P, Zelek, L, et al
The American journal of clinical nutrition. 2012;(4):944-50
-
-
Free full text
-
Abstract
BACKGROUND Mechanistic data suggest that n-3 PUFAs and endothelial function may interact and play a role in carcinogenesis, but epidemiologic evidence is lacking. OBJECTIVE Our objective was to investigate whether the prospective association between soluble intercellular adhesion molecule-1 (sICAM-1) and cancer risk is modulated by n-3 PUFA intake. DESIGN A nested case-control study was designed to include all first-incident cancer cases diagnosed in the SUpplémentation en VItamines et Minéraux AntioXydants cohort between 1994 and 2007, with available dietary data from 24-h records (n = 408). Cases were matched with 1 or 2 randomly selected controls (n = 760). Conditional logistic regression was used to estimate ORs and 95% CIs for the association between prediagnostic plasma concentrations of sICAM-1 and cancer risk, stratified by n-3 PUFA intake. The interactions between sICAM-1 and n-3 PUFA intake were tested. RESULTS An interaction was observed between sICAM-1 and n-3 PUFA intake, which was consistent across the studied cancer locations (P-interaction = 0.036 for overall, 0.038 for breast, and 0.020 for prostate cancer risk). sICAM-1 concentrations were positively associated with cancer risk among subjects with n-3 PUFA intakes below the median (multivariate OR(Tertile3vsTertile1): 2.8; 95% CI: 1.5, 5.2; P-trend = 0.001), whereas this association was not observed for subjects with n-3 PUFA intakes above the median (OR(Tertile3vsTertile1): 1.3; 95% CI: 0.8, 2.3; P-trend = 0.3). CONCLUSION These findings suggest that n-3 PUFA intake may counteract the procarcinogenic actions of sICAM-1.