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Biomedical subjects

James R Marshall

Publications and source records attributed to James R Marshall.

At least 19 recordsLinked to original sources
PubMed2006

Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies.

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 microg/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 microg/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 microg/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 microg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 microg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer.

Breast Neoplasms↗
PubMed2006

A permutation test for a weighted Kaplan-Meier estimator with application to the nutritional prevention of cancer trial.

The phenomenon of losing statistical significance with increasing follow-up can arise when a proportional hazard model is applied in a clinical trial where the impact of the intervention results in delaying a negative event such as cancer diagnosis, progression or death. Often parametric methods can be employed in such a setting, however, in studies where only a small percentage of subjects have an event, these methods are often inappropriate. We present an alternative method based on a weighted Kaplan-Meier estimator and a permutation test, and demonstrate its utility in the setting of the Nutritional Prevention of Cancer study where increasing follow-up resulted in loss of statistical significance for the ability of selenized yeast to prevent lung cancer.

Area Under Curve↗
PubMed2006

Regular analgesic use and risk of multiple myeloma.

Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but to date no previous research has focused on the role of analgesics in the etiology of multiple myeloma (MM). We conducted a hospital-based case-control study of 117 patients with primary, incident MM and 483 age and residence matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiological questionnaire. Participants who reported analgesic use at least once a week for at least 6 months were classified as regular users; individuals who did not use analgesics regularly served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Compared to non-users, regular aspirin users were not at reduced risk of MM (adjusted OR=0.99; 95% CI 0.65-1.49), nor were participants with the highest frequency or duration of aspirin use. A significant risk elevation was found for participants who were regular acetaminophen users (adjusted OR=2.95; 95% CI 1.72-5.08). Further, marked increases in risk of MM were noted with both greater frequency (>7 tablets weekly; adjusted OR=4.36; 95% CI 1.70-11.2) and greater duration (>10 years; adjusted OR=3.26; 95% CI 1.52-7.02) of acetaminophen use. We observed no evidence of a chemoprotective effect of aspirin on MM risk, but observed significant risk elevations with various measures of acetaminophen use. Our results warrant further investigation in population-based case-control and cohort studies and should be interpreted with caution in light of the limited sample size and biases inherent in hospital-based studies.

Acetaminophen↗
PubMed2006

Cancer and leukemia group B cancer control and health outcomes committee: origins and accomplishments.

Cancer and Leukemia Group B (CALGB) has conducted protocols in cancer prevention and control, psycho-oncology, and health services for many years. Significant findings from the studies have emerged and have helped shape the practice of medicine and the direction of future research in these areas. This article describes the origins of the Cancer Control and Health Outcomes Committee within CALGB and briefly describes significant findings and future work. The success CALGB has had with psycho-oncology and health services research has paved the way for other cooperative groups to develop these modalities. Cancer control research is growing and continues to gather momentum. This type of research is integral to providing quality care to patients and healthy populations.

Clinical Trials as Topic↗
PubMed2006

Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial.

Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow-up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow-up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination post-randomization during the follow-up period) or incident (identified at the second or subsequent examination). Ninety-nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43-1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09-0.77) and current smokers (OR = 0.27, 95% CI = 0.11-0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57-1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers.

Adenoma↗
PubMed2006

Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study.

PURPOSE: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue. EXPERIMENTAL DESIGN: We conducted a randomized, controlled, short-term trial of l-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer. The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV). We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. RESULTS: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics. Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. CONCLUSIONS: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium.

Adenocarcinoma↗
PubMed2006

Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial.

Despite the documented antioxidant and chemopreventive properties of selenium, studies of selenium intake and supplementation and cardiovascular disease have yielded inconsistent findings. The authors examined the effect of selenium supplementation (200 microg daily) on cardiovascular disease incidence and mortality through the entire blinded phase of the Nutritional Prevention of Cancer Trial (1983-1996) among participants who were free of cardiovascular disease at baseline (randomized to selenium: n = 504; randomized to placebo: n = 500). Selenium supplementation was not significantly associated with any of the cardiovascular disease endpoints during 7.6 years of follow-up (all cardiovascular disease: hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.37; myocardial infarction: HR = 0.94, 95% CI: 0.61, 1.44; stroke: HR = 1.02, 95% CI: 0.63, 1.65; all cardiovascular disease mortality: HR = 1.22, 95% CI: 0.76, 1.95). The lack of significant association with cardiovascular disease endpoints was also confirmed when analyses were further stratified by tertiles of baseline plasma selenium concentrations. These findings indicate no overall effect of selenium supplementation on the primary prevention of cardiovascular disease in this population.

Cardiovascular Diseases↗
PubMed2006

Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.

Adult↗
PubMed2005

Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers.

Our previous report showed that methylseleninic acid (MSA) significantly decreases the expression of androgen receptor and prostate-specific antigen (PSA) in LNCaP cells. The present study extended the above observations by showing the universality of this phenomenon and that the inhibitory effect of MSA on prostate cancer cell growth and cancer-specific biomarkers is mediated through androgen receptor down-regulation. First, MSA decreases the expression of androgen receptor and PSA in five human prostate cancer cell lines (LNCaP, LAPC-4, CWR22Rv1, LNCaP-C81, and LNCaP-LN3), irrespective of their androgen receptor genotype (wild type versus mutant) or sensitivity to androgen-stimulated growth. Second, by using the ARE-luciferase reporter gene assay, we found that MSA suppression of androgen receptor transactivation is accounted for primarily by the reduction of androgen receptor protein level. Third, MSA inhibition of five androgen receptor-regulated genes implicated in prostate carcinogenesis (PSA, KLK2, ABCC4, DHCR24, and GUCY1A3) is significantly attenuated by androgen receptor overexpression. Fourth, transfection of androgen receptor in LNCaP cells weakened noticeably the inhibitory effect of MSA on cell growth and proliferation. Androgen receptor signaling has been documented extensively to play an important role in the development of both androgen-dependent and -independent prostate cancer. Our finding that MSA reduces androgen receptor availability by blocking androgen receptor transcription provides justification for a mechanism-driven intervention strategy in using selenium to control prostate cancer progression.

Biomarkers, Tumor↗
PubMed2005

Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in western New York.

A number of epidemiological studies have suggested that diet may affect the etiology of prostate cancer, but few have investigated the impact of phytochemical intakes on this cancer. We conducted a case-control study of diet and prostate cancer in western New York involving 433 men with primary, histologically confirmed prostate cancer and 538 population-based controls, frequency matched to cases on age and county of residence. Diet was assessed with a detailed food-frequency questionnaire. We calculated daily intakes of nutrients and the phytochemicals beta-sitosterol, campesterol, stigmasterol, total phytosterols, total lignan precursors, quercetin, and kaempferol based on published food composition data. Odds ratios (ORs) and 95% confidence intervals (CIs) describing the association of prostate cancer risk with selected nutrients, phytochemicals, and food groups were estimated with unconditional logistic regression. Compared with men in the lowest quartile of intake, reduced risks were observed for men in the highest quartile of intake of vitamin C (OR = 0.49; 95% CI = 0.33-0.74), beta-carotene (OR = 0.53; 95% CI = 0.36-0.79), alpha-carotene (OR = 0.67; 95% CI = 0.47-0.97), lutein (OR = 0.55; 95% CI = 0.37-0.81), lycopene (OR = 0.62; 95% CI = 0.42-0.92), total lignan precursors (OR = 0.66; 95% CI = 0.47-0.94), quercetin (OR = 0.64; 95% CI = 0.44-0.92), and total vegetables (OR = 0.53; 95% CI = 0.36-0.79), but weak increased risks were observed for snacks and sweets (OR = 1.46; 95% CI = 0.95-2.23). Estimates associated with nutrients and phytochemicals were attenuated after adjustment for total vegetable intake. Nevertheless, our results support the hypothesis that a phytochemical-rich, plant-based diet is of importance in reducing risks of hormone-related neoplasms.

Aged↗
PubMed2004

Low energy reporting may increase in intervention participants enrolled in dietary intervention trials.

OBJECTIVE: To examine differences in low energy intake reporting between intervention and control groups during a dietary intervention trial. DESIGN: Retrospective data analysis from a subcohort of participants in the Polyp Prevention Trial (PPT), a 4-year, multisite, randomized, controlled dietary intervention trial. Intervention consisted of educational material and counseling sessions supporting a low-fat, high-fiber diet. Baseline and annual demographics, behavioral characteristics, energy intake (EI) based on self-reported 4-day food records, and height and weight of participants were collected at baseline and annually. Basal metabolic rate (BMR) was estimated (using the Schofield equation) to calculate EI/BMR. SUBJECTS: Of the 443 participants (302 male, 141 female) at baseline, 195 (43.3%) were younger than 60 years, and 394 (91%) were white. At Year 4, 383 participants remained: 186 (122 men, 64 women) in the intervention group, and 197 (133 men, 64 women) in the control group. STATISTICAL ANALYSES: Using either paired t tests or analysis of variance, the differences between the means for EI, weight, and EI/BMR were compared at baseline, Year 1, and Year 4 for the participants who remained at Year 4. The Goldberg EI/BMR cutoff value of 1.06 (for plausible EI) identified participants who reported low EI. Linear regression was used to quantify the association of various risk factors to EI/BMR and for multivariate analyses within groups. chi(2) contingency table analysis quantified differences of low energy reporting within groups. RESULTS: At baseline, 46.8% of women and 11.6% of men reported lower than plausible EI. Only men had a significant increase in low energy reporting after randomization. At Year 1, 18.9% of intervention group men reported low EI compared with 9.8% of control group men (P<.05). At Year 4, 23.0% of intervention group men reported low EI compared with 12.8% of control group men (P<.05). CONCLUSIONS/APPLICATIONS: Difference in low EI reporting between intervention and control groups could distort results from dietary intervention trials; interpretation of findings from dietary trials must include this potential bias. Intervention study design should include dietary intake data collection methods that are not subject to such bias (ie, biomarkers and performance criteria) to measure intervention compliance.

Basal Metabolism↗
PubMed2004

Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer.

In the US, prostate cancer (PCa) has the highest incidence rate of all cancers in males, with few known modifiable risk factors. Some studies support an association between the Vitamin D metabolites, 1,25-dihydroxyvitamin D (1alpha,25(OH)(2)D(3)) and/or 25-hydroxyvitamin D (25(OH)D(3)), and prostate cancer, while others have yielded conflicting results. 1alpha,25(OH)(2)D(3) has anti-proliferative and pro-differentiating effects in prostate cancer cell lines, and levels of circulating 25(OH)D(3) may be important as PCa cells possess 1-alpha-hydroxylase activity. Using a nested case-control design, we evaluated whether plasma levels of 25(OH)D(3) and 1alpha,25(OH)(2)D(3) were associated with prostate cancer risk in participants from the Nutritional Prevention of Cancer (NPC) trial. With 83 cases and 166 matched controls, we calculated the adjusted odds ratios for increasing plasma levels of 25(OH)D(3) and 1alpha,25(OH)(2)D(3). Compared to the lowest tertile of plasma 25(OH)D(3) levels, the adjusted odds ratios were 1.71 (0.68-4.34) and 0.75 (0.29-1.91); the corresponding odds ratios for 1alpha,25(OH)(2)D(3) were 1.44 (0.59-3.52) and 1.06 (0.42-2.66). Given the pivotal effects of the Vitamin D receptor on gene transcription, it is likely that the anti-carcinogenic effects of Vitamin D that have previously been described are related to the activity and expression of the Vitamin D receptor and should be investigated further.

Aged↗
PubMed2004

A report of high-dose selenium supplementation: response and toxicities.

Concerns about the toxicity of selenium has limited the doses used in chemoprevention. Based on previous studies, intakes of 400 microg/day and plasma selenium of 1000 ng/ml (Dietary Reference Intakes, Academy Press, New York, 2000, p. 384) were established as the no observed adverse effect level (NOAEL). This investigation summarizes the plasma response and toxicity reports from 24 men with biopsy-proven prostate cancer who were randomized to either 1600 or 3200 microg/day of selenized yeast as part of a controlled clinical trial testing selenium as a chemopreventive agent for prostate cancer progression. Subjects were on these doses for averages of almost 12 months. Plasma selenium levels were monitored throughout the course of follow-up. Symptoms of selenium toxicity were assessed by patient interview with specific questions regarding breath, hair and nail changes. Several liver and kidney function tests and hematology were measured at 6-month intervals. 8 subjects were randomized to the 1600 microg/day and 16 to the 3200 microg/day group. The mean plasma selenium levels achieved with supplementation were 492.2 ng/ml (SD = 188.3) and 639.7 ng/ml (SD = 490.7) for the 1600 and 3200 microg/ day doses, respectively. The 3200 microg/day group reported more selenium-related side effects. Blood chemistry and hematology results were all within normal limits for both treatment groups. More subjects on 3200 microg/day reported symptoms of selenium toxicity; however, these reports did not correspond to peaks in plasma selenium levels. We observed no obvious selenium-related serious toxicities. As selenium is used in more chemoprevention and therapeutic settings, additional information on selenium species, sequestration of selenium in specific organs, excretion, and toxicities is needed.

Aged↗
PubMed2004

Wheat bran fiber supplementation and bone loss among older people.

OBJECTIVE: The purpose of this study was to investigate the effect of wheat bran fiber (WBF) supplementation on bone loss in older people. METHODS: Two hundred thirty-seven men and women ages 40 to 80 y were included in this study. They constituted a subgroup of participants from a 3-y WBF intervention trial for preventing recurrence of colorectal adenomas. These participants were randomized into a high (13.5 g/d) or a low (2 g/d) WBF supplementation group. Bone mineral density at the forearm was measured by single photon absorptiometry at baseline and yearly during the intervention to monitor possible toxic effects of fiber supplementation on bone metabolism. RESULTS: Baseline characteristics of this subgroup of participants from the WBF trial were similar between the high and low supplementation groups. The annual amounts of bone loss at the radial third site were -0.017 +/- 0.018 g/cm2 and -0.013 +/- 0.021 g/cm2, respectively, for the low and high WBF groups; and the annual bone losses at the ultra-distal site were was -0.005 +/- 0.020 g/cm2 and -0.006 +/- 0.027 g/cm2, respectively, for the low and high WBF groups. After controlling for confounding factors, we found no significant differences in bone loss between groups (P > 0.05). CONCLUSION: WBF supplementation at the level given in this study may not have a significant effect on bone loss among older people.

Absorptiometry, Photon↗
PubMed2004

Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype.

The role of vegetable consumption in relation to breast cancer risk is controversial. Anticarcinogenic compounds may be present only in specific vegetables, thereby attenuating findings for total vegetable intake. Cruciferous vegetables contain precursors of isothiocyanates (ITCs), which may be chemopreventive through potent inhibition of phase I, and induction of phase II enzymes, such as glutathione S-transferases (GSTs). We investigated associations between consumption of cruciferous vegetables, sources of ITCs, and breast cancer risk, and potential modification of relations by GSTM1 and GSTT1 genotypes. Cases (n = 740) were Caucasian women with incident breast cancer identified from all major hospitals in Erie and Niagara counties. Community controls (n = 810) were frequency matched to cases by age and county. An in-depth interview including a validated FFQ was administered in person. Odds ratios (ORs) and 95% CIs were used to estimate relative risks. Consumption of cruciferous vegetables, particularly broccoli, was marginally inversely associated with breast cancer risk in premenopausal women [4th quartile OR = 0.6, 95% CI (0.40-1.01), P = 0.058]. Associations were weaker or null among postmenopausal women. No significant effects of GST genotype on risk were observed in either menopausal group. These data indicate that cruciferous vegetables may play an important role in decreasing the risk of premenopausal breast cancer.

Brassica↗
PubMed2004

On the importance of using multiple methods of dietary assessment.

BACKGROUND: Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial. METHODS: Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method. RESULTS: In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error. CONCLUSION: These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.

Adult↗
PubMed2004

Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk.

Cruciferous vegetables contain anticarcinogenic isothiocyanates (ITCs), particularly the potent sulforaphane, which may decrease risk of prostate cancer through induction of phase II enzymes, including glutathione S-transferases (GSTs). We evaluated this hypothesis in a population-based, case-control study of prostate cancer, including 428 men with incident prostate cancer and 537 community controls. An in-person interview included an extensive food-frequency questionnaire. Genotyping for deletions in GSTM1 and GSTT1 was performed in a subset of men who provided blood. Intakes of cruciferous vegetables and of broccoli, the greatest source of sulforaphane, were associated with decreased prostate cancer risk at all levels above the lowest consumers [adjusted 4th quartile odds ratio (OR)=0.58; 95% confidence interval (CI)=0.38, 0.89, and 0.72 (95% CI=0.49, 1.06)], respectively. In relation to genotypes, there was a nonsignificant increase in risk with the GSTT1 null genotype (OR=1.51; 95% CI=0.98, 2.31) but no effects of GSTM1 genotype. However, men with GSTM1-present genotype and high broccoli intake had the greatest reduction in risk (OR=0.49; 95% CI=0.27, 0.89). Our findings provide evidence that two or more servings per month of cruciferous vegetables may reduce risk of prostate cancer, especially among men with GSTM1-present alleles, and are consistent with a role of dietary ITCs as chemopreventive agents against prostate cancer.

Aged↗