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Non-supplemental carotenoids and retinol may potentiate antioxidant and anti-inflammatory mechanisms. Chronic intraprostatic inflammation is linked to prostate carcinogenesis. We investigated the association of circulating carotenoids and retinol with intraprostatic inflammation in benign tissue. We included 235 men from the Prostate Cancer Prevention Trial placebo arm who had a negative end-of-study biopsy, most (92.8%) done without clinical indication. α-carotene, β-carotene, β-cryptoxanthin, lycopene, and retinol were assessed by high-performance liquid chromatography using pooled year 1 and 4 serum. Presence and extent of intraprostatic inflammation in benign tissue was assessed in 3 (of 6-10) biopsy cores. Logistic (any core with inflammation vs none) and polytomous logistic (some or all cores with inflammation vs none) regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of intraprostatic inflammation by concentration tertile adjusting for age, race, prostate cancer family history, and serum cholesterol. None of the carotenoids or retinol was associated with intraprostatic inflammation, except β-cryptoxanthin, which appeared to be positively associated with any core with inflammation [vs none, T2: OR (95% CI) = 2.67 (1.19, 5.99); T3: 1.80 (0.84, 3.82), P-trend = 0.12]. These findings suggest that common circulating carotenoids and retinol are not useful dietary intervention targets for preventing prostate cancer via modulating intraprostatic inflammation.

Inconsistent results from epidemiologic studies of circulating fatty acids and prostate cancer risk may be partly due to use of blood concentrations as surrogate biomarkers of prostate tissue concentrations. To determine whether blood concentrations reflect prostate tissue fatty acid profiles, we evaluated associations between phospholipid fatty acid (PLFA) profiles measured in plasma and prostate tissue from 20 patients who underwent prostatectomy. For each patient, three prostate tissue specimens varying in size and location were collected. Correlations were calculated between a) tissue specimens by size ( ≤ 20 mg, > 20 mg); b) individual tissue samples [Intraclass Correlation Coefficient (ICC)]; and c) plasma and mean tissue PLFA concentrations. PLFA concentrations from ≤ 20 mg and > 20 mg tissues were nearly identical. For most PLFAs, intra-individual correlations between tissue specimens were moderate to strong (linoleic acid = 0.66, eicosapentaenoic acid = 0.96), with only one ICC below 0.50 (trans-fatty acid 18:2, ICC = 0.28). Most correlations of mean tissue and plasma concentrations were moderate to strong (α-linoleic acid = 0.47, eicosapentaenoic acid = 0.93). PLFA concentrations are largely homogeneous within the prostate and can be reliably measured in small quantities of tissue. The overall strong correlations between plasma and tissue suggest that for most individual PLFAs, plasma concentrations are adequate surrogate markers of prostate tissue concentrations.

Most epidemiologic studies of circulating phospholipid fatty acids (PLFAs) and disease risk have used the relative concentration (percentage of total) of each fatty acid as the measure of exposure. Using relative concentrations, the total of all fatty acids is summed to 100% and thus the values of individual fatty acid are not independent. This has led to debate, along with the suggestion to use absolute concentrations of fatty acids. We aimed to examine the relationship between relative (weight percentage) and absolute (mg/L) concentrations of individual circulating PLFAs.Relative and absolute concentrations of 41 circulating PLFAs were measured by gas chromatography in samples from 3 diverse populations. Correlations between the relative and absolute concentrations for each fatty acid were used to measure agreement. Unadjusted correlations and correlations adjusting absolute PLFA concentrations for total cholesterol were calculated.Unadjusted correlations between relative and absolute concentrations, as well as correlations adjusting absolute PLFA concentrations for total cholesterol, were high for most PLFAs in all 3 studies. Across the 3 studies, 28 of the 41 analyzed PLFAs had unadjusted correlations0.6 and 39 had adjusted correlations0.6.Choice of relative vs absolute concentration may not affect interpretation of results for most circulating PLFAs in studies of association between individual PLFAs and disease outcomes, especially if a covariate reflecting total lipids, such as total circulating cholesterol, is included in the model. However, for fatty acids, such as 16:0 (palmitic acid), with low correlation between the 2 metrics, using relative vs absolute concentration may lead to different inferences regarding their association with the outcome. Because both concentrations could be obtained simultaneously from the same laboratory assay, use of both metrics is warranted to better understand PLFA-disease relationships.

DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994–1995), peri- (1996–1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.

Effective strategies for reducing food intake are needed to reduce risk of obesity-related cancers. We investigated the effect of low and high glycemic load (GL) diets on satiety and whether satiety varied by body mass index (BMI), gender, and serum leptin. Eighty normal weight (BMI = 18.5-24.9 kg/m²) and overweight/ obese (BMI = 28.0-40.0 kg/m²) adults participated in a randomized, crossover controlled feeding study testing low GL vs. high GL diets. The 28-day diets were isocaloric with identical macronutrient distributions, differing only in GL and fiber. Participants completed visual analog satiety surveys and fasting serum leptin after each 28-day period. T-tests compared mean within- and between-person satiety scores and leptin values. Participants reported 7% greater satiation on the low GL vs. the high GL diet (P = 0.03) and fewer food cravings on the low GL vs. the high GL diet (P < 0.001). Compared to males, females reported less hunger (P = 0.05) and more satiety on the low GL vs. the high GL diet (P < 0.01). Participants with low body fat (

Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women's Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92-1.29 (P for trend = 0.27); 1.01, 0.91-1.12 (P = 0.74); and 0.95, 0.80-1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94-2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.

Evidence is inconsistent regarding whether dietary fat influences sex hormone concentrations. This issue is important for breast cancer survivors since clinical recommendations suggest maintaining low hormone levels primarily via pharmacologic agents. This study examines associations between dietary fat and circulating sex hormones among participants in the Health, Eating, Activity and Lifestyle (HEAL) Study, a cohort of breast cancer survivors (N = 511). During a postdiagnosis interview, detailed data were collected on diet, physical activity, lifestyle habits, and medication use (including tamoxifen). Staff measured height and weight and collected fasting bloods. Multivariate linear regression modeled associations of dietary fat with serum sex hormones. Among women using tamoxifen, we observed modest inverse associations of dietary fat with estrone (P < 0.01), estradiol (P < 0.05), testosterone (P < 0.01), free testosterone (P < 0.01), and DHEA (P < 0.01) for higher vs. lower fat intake; but there was no evidence for a trend. Associations were consistent across measures (percent energy from fat, total, saturated, and polyunsaturated fat), and modest effect modification was observed between fat intake and tamoxifen in relation to hormones. Among women not using tamoxifen, fat intake was not associated with hormone concentrations. Further work is needed to confirm the findings and to understand the clinical implications of these observations.

Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling (P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk.

High dietary intake of fruits and vegetables is consistently associated with a reduced risk of common human cancers, including cancers of the lung, breast, prostate, and colon. It is unknown which bioactive compound or compounds in plant foods provide the chemoprotective effects. One class of compounds currently under investigation is flavonoids, a large group of compounds with similar structure, consisting of two phenolic benzene rings linked to a heterocyclic pyran or pyrone. Although there are numerous in vitro and animal model data suggesting that flavonoids influence important cellular and molecular mechanisms related to carcinogenesis, such as cell cycle control and apoptosis, there are limited data from human population studies. This article reviews data from four cohort studies and six case-control studies, which have examined associations of flavonoid intake with cancer risk. There is consistent evidence from these studies that flavonoids, especially quercetin, may reduce the risk of lung cancer. Further research using new dietary databases for food flavonoid content is needed to confirm these findings before specific public health recommendations about flavonoids can be formulated.