Cooney, Robert V.

Permanent URI for this collectionhttps://hdl.handle.net/10125/24277

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Inhibition of colonic aberrant crypt formation by the dietary flavonoids (+)-catechin and hesperidin.
(2002) Franke, Adrian A.; Custer, Laurie J.; Cooney, Robert V.; Tanaka, Yuichiro; Xu, Meirong; Dashwood, Roderick H.
The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain.
(2002-03) Williamson, Kelly S.; Gabbita, S Prasad; Mou, Shenyun; West, Melinda; Pye, Quentin N.; Markesbery, William R.; Cooney, Robert V.; Grammas, Paula; Reimann-Philipp, Ulrich; Floyd, Robert A.; Hensley, Kenneth
Oxidative stress and quasi-inflammatory processes recently have been recognized as contributing factors in the pathogenesis of Alzheimer's disease (AD). Reactive nitrating species have specifically been implicated in AD based on immunochemical and instrumental detection of nitrotyrosine in AD brain protein. The significance of lipid-phase nitration has not been investigated in AD. This study documents a significant two- to threefold increase in the lipid nitration product 5-nitro-gamma-tocopherol in affected regions of the AD brain as determined by high-performance liquid chromatography with electrochemical detection. In a bioassay to compare the relative potency of alpha-tocopherol and gamma-tocopherol against nitrative stress, rat brain mitochondria were exposed to the peroxynitrite-generating compound SIN-1. The oxidation-sensitive Kreb's cycle enzyme alpha-ketoglutarate dehydrogenase was inactivated by SIN-1, in a manner that could be significantly attenuated by gamma-tocopherol (at <10 microM) but not by alpha-tocopherol. These data indicate that nitric oxide-derived species are significant contributors to lipid oxidation in the AD brain. The findings are discussed in reference to the neuroinflammatory hypothesis of AD and the possible role of gamma-tocopherol as a major lipid-phase scavenger of reactive nitrogen species.
Bioavailability and antioxidant effects of orange juice components in humans.
(2005-06) Franke, Adrian A.; Cooney, Robert V.; Henning, Susanne M.; Custer, Laurie J.
Seven healthy females and six males consumed daily 256 mg of vitamin C, 271 mg of flavanones (mainly as glycosides), 6 mg of carotenoids (mainly xanthophylls and cryptoxanthins), and 0.16 mg of folate by incorporation of daily three times 236 mL of not from concentrate orange juice (OJ) into their habitual diet. At the end of 3 weeks, mean vitamin C, folate, carotenoid, and flavanone plasma concentrations increased significantly relative to baseline by 59% (p < 0.001), 46% (p = 0.018), and 22% (p < 0.001), and 8-fold (p = 0.045), respectively. Flavanones were excreted in urine 9-fold more at the end of the intervention (p = 0.01) but returned to baseline 2 days after study completion. After the 3 week intervention, plasma concentrations of vitamins A and E did not change. 8-Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11), and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7), respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric acid reactive substance plasma concentrations did not change significantly. We conclude from this pilot study that OJ is an excellent food source to enhance circulating concentrations of valuable hydrophilic as well as lipophilic phytochemicals.
Tocopherols and prostate cancer.
(2006-09) Cooney, Robert V.
Enhancement of intracellular gamma-tocopherol levels in cytokine-stimulated C3H 10T1/2 fibroblasts: relation to NO synthesis, isoprostane formation, and tocopherol oxidation.
(2007) Tanaka, Yuichiro; Wood, Leslie A Lesoon; Cooney, Robert V.
Stimulation of C3H 10T1/2 murine fibroblasts with interferon-gamma(IFN) and bacterial lipopolysaccharide (LPS) generates reactive oxygen and nitrogen species leading to DNA damage, lipid oxidation, and tocopherol oxidation. The tocopherols possess unique chemical and biological properties that suggest they have important roles related to intracellular defense against radical-mediated damage.
Association of leptin, 25-hydroxyvitamin D, and parathyroid hormone in women.
(2009) Maetani, Micah; Maskarinec, Gertraud; Franke, Adrian A.; Cooney, Robert V.
Vitamin D deficiency and adipocytokines have been implicated in the etiology of aging-related diseases such as cancer, osteoporosis, and diseases of the cardiovascular system. The association between elevated parathyroid hormone (PTH) and low 25-hydroxyvitamin D (25-OH-VitD) in plasma is used to define vitamin D deficiency, yet their associated mechanistic pathways are unclear. Utilizing plasma samples from women in a previous intervention study, we measured plasma 25-OH-VitD, leptin, adiponectin, PTH, and lipid levels. We observed strong positive associations for leptin with PTH, gamma -tocopherol, and body mass index (BMI) and inverse associations with 25-OH-VitD and adiponectin. Although commonly accepted that vitamin D deficiency causes hyperparathyroidism, we observed this association primarily in individuals with elevated leptin levels, suggesting that leptin may be an important modifier of this effect consistent with 25-OH-VitD-mediated inhibition of leptin. Leptin was highly correlated with the BMI/25-OH-VitD ratio (r = 0.80; P < 0.0001), consistent with a model in which BMI (adiposity) and 25-OH-VitD are the primary determinants of circulating leptin and PTH levels. This model may explain the failure of some studies to observe elevated PTH in vitamin D deficient adolescents and provides important insight into epidemiological studies exploring the associations of these individual biomarkers with chronic disease risk and mortality.
Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study.
(2009) Epplein, Meira; Shvetsov, Yurii B.; Wilkens, Lynne R.; Franke, Adrian A.; Cooney, Robert V.; Le Marchand, Loïc; Henderson, Brian E.; Kolonel, Laurence N.; Goodman, Marc T.
Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk.
Inflammatory markers in a 2-year soy intervention among premenopausal women.
(2009) Maskarinec, Gertraud; Steude, Jana S.; Franke, Adrian A.; Cooney, Robert V.
Epidemiologic evidence supports a role of soy foods in breast cancer etiology. Because chronic inflammation appears to be a critical component in carcinogenesis, we examined the potential anti-inflammatory effects of soy foods.
Association of plasma micronutrient levels and urinary isoprostane with risk of lung cancer: the multiethnic cohort study.
(2009-07) Epplein, Meira; Franke, Adrian A.; Cooney, Robert V.; Morris, J. Steven; Wilkens, Lynne R.; Goodman, Marc T.; Murphy, Suzanne P.; Henderson, Brian E.; Kolonel, Laurence N.; Le Marchand, Loïc
Although smoking is the primary risk factor for lung cancer, there is evidence to suggest that fruit and vegetable intake are important cofactors. The present case-control study, nested within the Multiethnic Cohort Study, examined the associations of biomarkers of fruit and vegetable intake (individual plasma micronutrient levels), serum selenium, and a urinary biomarker for total lipid peroxidation with lung cancer risk. Two hundred seven incident cases were matched to 414 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection, and hours of fasting. We measured prediagnositic circulating levels of individual tocopherols and carotenoids, retinol, and serum selenium, and urinary 15-isoprostane F(2t). Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI). For men, strong reductions in risk were seen with increasing tertiles of each plasma carotenoid, with the ORs for the third tertile, compared with the first tertile, ranging from 0.24 to 0.45 (P(trends), 0.002-0.04). No associations were found among women for carotenoids or among either sex for tocopherols, selenium, and retinol. A doubling in risk was seen for men in the second and third tertiles, compared with the first tertile of urinary 15-isoprostane F(2t) (OR, 2.31; 95% CI, 1.02-5.25; and OR, 2.16; 95% CI, 0.98-4.78). This study supports the previously observed association between circulating carotenoids and lung cancer risk in men, and adds to the limited literature regarding urinary 15-isoprostane F(2t) as a marker of cancer risk. Future research examining the possible relationship between isoprostanes and lung cancer is warranted.
Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F(2t) in serum or urine with prostate cancer risk: the multiethnic cohort.
(2009-09) Gill, Jasmeet K.; Franke, Adrian A.; Morris, J. Steven; Cooney, Robert V.; Wilkens, Lynne R.; Le Marchand, Loic; Goodman, Marc T.; Henderson, Brian E.; Kolonel, Laurence N.
We examine the association of antioxidants and 15-isoprostane F(2t) with risk of prostate cancer.
The relation of leptin and adiponectin with breast density among premenopausal women.
(2010-01) Maskarinec, Gertraud; Woolcott, Christy; Steude, Jana S.; Franke, Adrian A.; Cooney, Robert V.
The adipocytokine leptin may increase breast cancer risk, while adiponectin may be protective. We examined the association of the two circulating markers with mammographic density, a strong predictor of breast cancer risk. For 183 premenopausal participants of a nutritional trial, mammograms performed at baseline, year 1 and year 2 were assessed for density using a computer-assisted method. Serum samples obtained at the same time were analyzed for leptin and adiponectin by enzyme-linked immunosorbent assay. We applied mixed models to incorporate the repeated measurements while adjusting for confounders including body mass index (BMI). At baseline, the mean age of the participants was 42.6+/-2.9 years; 40% were of Asian ancestry. Leptin was lower and adiponectin higher in normal weight than overweight women. Neither marker was related to absolute breast density. The significant inverse association of leptin with percent density disappeared when BMI was added to the model. After stratification by weight, percent density decreased with higher leptin levels in normal weight women, whereas it increased among overweight participants. After adjustment for BMI, the positive association between percent density and adiponectin was greatly reduced and no longer significant. These results do not support a strong association of leptin or adiponectin with breast cancer risk as assessed by mammographic density. In contrast, the findings suggest the possibility that the inverse association of BMI with breast cancer risk in premenopausal women is mediated by adipocytokines.
Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort.
(2010-03) Park, Song-Yi; Cooney, Robert V.; Wilkens, Lynne R.; Murphy, Suzanne P.; Henderson, Brian E.; Kolonel, Laurence N.
The purpose of this study was to examine the relationship of plasma 25-hydroxyvitamin D (25(OH)D) concentrations to prostate cancer within a large multiethnic cohort in Hawaii and California using a nested case-control design. The study included 329 incidents of prostate cancer of African American, Native Hawaiian, Japanese, Latino and White ancestry, and 656 controls matched on age, race/ethnicity, date/time of blood collection and fasting status. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). No association with prostate cancer risk was found in an analysis based on quartiles of 25(OH)D. When clinically defined cutpoints were used, there was no increased risk for the lowest 25(OH)D concentration (OR for <20 versus 30-<50ng/ml=1.10, 95% CI=0.68-1.78), while there was a suggestive increased risk for higher concentrations (OR for 50ng/ml=1.52, 95% CI=0.92-2.51). The findings from this prospective study of men in the Multiethnic Cohort do not support the hypothesis that vitamin D lowers the risk of prostate cancer. Further follow-up is warranted to determine whether the findings are consistent across ethnic groups.
Associations between obesity and serum lipid-soluble micronutrients among premenopausal women.
(2010-04) Chai, Weiwen; Conroy, Shannon M.; Maskarinec, Gertraud; Franke, Adrian A.; Pagano, Ian S.; Cooney, Robert V.
Elucidating potential pathways that micronutrients may reduce/promote chronic disease may contribute to our understanding of the underlying etiology of disease and their utility as markers of risk. In the current study, we examined associations of serum lipid-soluble micronutrients with body mass index (BMI). We hypothesized that obesity may differentially influence serum micronutrient levels, thereby affecting risk for chronic disease incidence and mortality. Baseline serum samples from 180 premenopausal women from a nutritional trial were analyzed for leptin, C-reactive protein, 25-hydroxyvitamin D, carotenoids, and tocopherols. Participants were stratified into normal-weight (18.5-24.9), overweight (25-29.9), and obese (>or=30) subgroups by BMI (in kilograms per square meter). Differences in serum biomarkers among BMI subgroups were adjusted for Asian ethnicity and smoking status. As expected, obese individuals had significantly higher serum levels of leptin and C-reactive protein (Ps < .05) compared with normal-weight women. gamma-Tocopherol levels were significantly higher in obese individuals (P < .05), whereas alpha-tocopherol levels did not differ among BMI subgroups. Serum levels of 25-hydroxyvitamin D and carotenoids (except lycopene) were significantly lower in obese than in normal-weight women (Ps < .05). The associations between BMI and carotenoids were independent of dietary intake. The obesity-associated reduction for total provitamin A carotenoids (45%) was approximately 3-fold greater than that observed for non-provitamin A carotenoids (16%). Our results indicate potential influences of obesity on serum levels of lipid-soluble micronutrients and suggest that metabolism of provitamin A carotenoids may contribute to the differences observed.
Coenzyme Q10 in human blood: native levels and determinants of oxidation during processing and storage.
(2010-06) Franke, Adrian A.; Morrison, Cynthia M.; Bakke, Jesse L.; Custer, Laurie J.; Li, Xingnan; Cooney, Robert V.
Coenzyme Q10 (Q10) is present in the circulation mainly in its reduced form (ubiquinol-10; UL10), but oxidizes quickly ex vivo to ubiquinone-10 (UN10). Therefore, native UL10:UN10 ratios, used as markers of redox status and disease risk, are difficult to measure. We established an RP-(U)HPLC method with coulometric detection to measure natively circulating UL10 and UN10 concentrations by adding a ubiquinol/ubiquinone mixture as an internal standard immediately after plasma preparation. This allowed adjustment for unavoidable artificial UL10 oxidation as well as for total losses (or gains) of analytes during sample storage, processing, and analysis because the internal standards exactly paralleled the chemical behavior of Q10. This technique applied to blood (n = 13) revealed Q10 levels of 680-3300 nM with a mean UL10:UN10 ratio of 95:5, which was inversely associated with total Q10 (r=-0.69; p=0.004). The oxidation of UL10 to UN10 was equimolar, increased by O(2), and decreased by lower temperatures or various degassing methods. Although UL10 was stable in blood or when pure in organic solvents at 22 degrees C, its oxidation was catalyzed dose dependently by alpha-tocopherol and butylated hydroxytoluene, particularly when present in combination. Key structural features for the catalytic pro-oxidant properties of phenolic antioxidants included two substituents vicinal to the phenolic hydroxyl group.
Plasma coenzyme Q10 levels and postmenopausal breast cancer risk: the multiethnic cohort study.
(2010-09) Chai, Weiwen; Cooney, Robert V.; Franke, Adrian A.; Shvetsov, Yurii B.; Caberto, Christian P.; Wilkens, Lynne R.; Le Marchand, Loïc; Henderson, Brian E.; Kolonel, Laurence N.; Goodman, Marc T.
Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and is considered an important cellular antioxidant. Decreased circulating CoQ10 levels have been reported in women with breast cancer, but evidence is limited. We examined the association of plasma CoQ10 levels with postmenopausal breast cancer risk using prospectively collected blood samples.
Leptin, adiponectin, and obesity among Caucasian and Asian women.
(2011) Conroy, Shannon M.; Chai, Weiwen; Lim, Unhee; Franke, Adrian A.; Cooney, Robert V.; Maskarinec, Gertraud
Ethnic differences in adipose tissue distribution may contribute to different chronic disease risks across ethnic groups, and adipokines may mediate the risk. In a cross-sectional study, we examined ethnic differences in adipokines and inflammatory markers as related to body mass index (BMI) among 183 premenopausal women with Caucasian and Asian ancestry. General linear models were used to estimate adjusted mean levels of leptin, adiponectin, interleukin-6, and C-reactive protein (CRP). Asian women had significantly lower serum levels of leptin, adiponectin, and CRP than Caucasian participants (P≤.01) across all levels of BMI. Among overweight and obese women, Asians showed a stronger association of CRP with leptin (β=1.34 versus β=0.64) and with adiponectin (β=-0.95 versus β=-0.75) than Caucasians. Compared to Caucasians of similar BMI, Asians may experience a higher chronic disease risk due to lower levels of adiponectin despite their lower levels of leptin.
Plasma coenzyme Q10 levels and prostate cancer risk: the multiethnic cohort study.
(2011-04) Chai, Weiwen; Cooney, Robert V.; Franke, Adrian A.; Caberto, Christian P.; Wilkens, Lynne R.; Le Marchand, Loïc; Goodman, Marc T.; Henderson, Brian E.; Kolonel, Laurence N.
Coenzyme Q10 (CoQ10) is considered to be a potential anticancer agent, but epidemiologic evidence regarding CoQ10 and prostate cancer risk is lacking. We examined the association of circulating CoQ10 levels with prostate cancer risk, using prediagnostic blood samples.
Low plasma coenzyme Q(10) levels and breast cancer risk in Chinese women.
(2011-06) Cooney, Robert V.; Dai, Qi; Gao, Yu-Tang; Chow, Wong-Ho; Franke, Adrian A.; Shu, Xiao-Ou; Li, Honglan; Ji, Butian; Cai, Qiuyin; Chai, Weiwen; Zheng, Wei
Low circulating levels of coenzyme Q(10) (CoQ(10)) have been associated with increased cancer incidence and poor prognosis for a number of cancer types, while a recent prospective study observed a positive association for CoQ(10) with breast cancer risk.
Predicting total, abdominal, visceral and hepatic adiposity with circulating biomarkers in Caucasian and Japanese American women.
(2012) Lim, Unhee; Turner, Stephen D.; Franke, Adrian A.; Cooney, Robert V.; Wilkens, Lynne R.; Ernst, Thomas; Albright, Cheryl L.; Novotny, Rachel; Chang, Linda; Kolonel, Laurence N.; Murphy, Suzanne P.; Le Marchand, Loïc
Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.
UH Cancer Center hotline: modern medicine and the road to prevention: a long and tortuous path.
(2012-02) Cooney, Robert V.

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