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Brasky T.M.,Ohio State University | Darke A.K.,Statistical Center | Song X.,Cancer Prevention Program | Tangen C.M.,Statistical Center | And 11 more authors.
Journal of the National Cancer Institute | Year: 2013

BackgroundStudies of dietary ω-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood concentrations of long-chain ω-3 polyunsaturated fatty acids ([LCω-3PUFA] 20:5ω3; 22:5ω3; 22:6ω3]. This case-cohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.MethodsCase subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.ResultsCompared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response.ConclusionsThis study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks. © 2013 The Author.


Moinpour C.M.,Cancer Prevention Program | Moinpour C.M.,University of Washington | Darke A.K.,Fred Hutchinson Cancer Research Center | Donaldson G.W.,University of Utah | And 8 more authors.
Journal of the National Cancer Institute | Year: 2012

Background The Prostate Cancer Prevention Trial (PCPT)a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate canceroffered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial. MethodsWe assessed three health-related quality-of-life domains (measured with the Health Survey Short Form36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided. ResultsFor the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] =-0.28 to 0.42, P =. 71). Comorbidities such as congestive heart failure (estimate =-5.64, 95% CI =-7.96 to-3.32, P <. 001), leg pain (estimate =-2.57, 95% CI =-3.04 to-2.10, P <. 001), and diabetes (estimate =-1.31, 95% CI =-2.04 to-0.57, P <. 001) had statistically significant negative effects on physical function, as did current smoking (estimate =-2.34, 95% CI =-2.97 to-1.71, P <. 001) and time on study (estimate =-1.20, 95% CI =-1.36 to-1.03, P <. 001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points. ConclusionFinasteride did not negatively affect SF36 Physical Functioning, Mental Health, or Vitality scores. © 2012 The Author.


PubMed | Cancer Prevention Program, Biostatistics and Biomathematics Program and., Fred Hutchinson Cancer Research Center and Cancer Prevention Program.
Type: Journal Article | Journal: The Journal of nutrition | Year: 2015

The consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations.We examined the association between variation across the genome and serum concentrations of lycopene in a multiethnic population.Participants included African (n = 914), Hispanic (n = 464), and European (n = 1203) American postmenopausal women from the Womens Health Initiative. We analyzed 7 million single nucleotide polymorphisms (SNPs). Linear regression models were used to assess associations between each SNP and serum concentrations (log transformed, continuous) of lycopene; we adjusted for age, body mass index, and population substructure. Models were run separately by ethnicity, and results were combined in a transethnic fixed-effects meta-analysis.In the meta-analysis, the scavenger receptor class B, member 1 (SCARB1) gene, which encodes for a cholesterol membrane transporter, was significantly associated with lycopene concentrations (rs1672879; P < 2.68 10(-9)). Each additional G allele resulted in a 12% decrease in lycopene concentrations for African Americans, 20% decrease for Hispanic Americans, and 9% decrease for European Americans. In addition, 2 regions were significantly associated with serum lycopene concentrations in African Americans: the slit homolog 3 gene (SLIT3), which serves as a molecular guidance cue in cellular migration, and the dehydrogenase/reductase (SDR family) member 2 (DHRS2) gene, which codes for an oxidoreductase that mitigates the breakdown of steroids.We found 3 novel loci associated with serum lycopene concentrations, 2 of which were specific to African Americans. Future functional studies looking at these specific genes may provide insight into the metabolism and underlying function of lycopene in humans, which may further elucidate lycopenes influence on disease risk and health. This trial was registered at clinicaltrials.gov as NCT00000611.

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