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A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma

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Abstract

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03-1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23-4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

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Background: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. Methods: Data on new cancer diagnoses during 2001 through 2016 were obtained from the Centers for Disease Control and Prevention-funded and National Cancer Institute-funded population-based cancer registry programs and compiled by the North American Association of Central Cancer Registries. Data on cancer deaths during 2001 through 2017 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in incidence and death rates for all cancers combined and for the leading cancer types by sex, racial/ethnic group, and age were estimated by joinpoint analysis and characterized by the average annual percent change during the most recent 5 years (2012-2016 for incidence and 2013-2017 for mortality). Results: Overall, cancer incidence rates decreased 0.6% on average per year during 2012 through 2016, but trends differed by sex, racial/ethnic group, and cancer type. Among males, cancer incidence rates were stable overall and among non-Hispanic white males but decreased in other racial/ethnic groups; rates increased for 5 of the 17 most common cancers, were stable for 7 cancers (including prostate), and decreased for 5 cancers (including lung and bronchus [lung] and colorectal). Among females, cancer incidence rates increased during 2012 to 2016 in all racial/ethnic groups, increasing on average 0.2% per year; rates increased for 8 of the 18 most common cancers (including breast), were stable for 6 cancers (including colorectal), and decreased for 4 cancers (including lung). Overall, cancer death rates decreased 1.5% on average per year during 2013 to 2017, decreasing 1.8% per year among males and 1.4% per year among females. During 2013 to 2017, cancer death rates decreased for all cancers combined among both males and females in each racial/ethnic group, for 11 of the 19 most common cancers among males (including lung and colorectal), and for 14 of the 20 most common cancers among females (including lung, colorectal, and breast). The largest declines in death rates were observed for melanoma of the skin (decreasing 6.1% per year among males and 6.3% among females) and lung (decreasing 4.8% per year among males and 3.7% among females). Among children younger than 15 years, cancer incidence rates increased an average of 0.8% per year during 2012 to 2016, and cancer death rates decreased an average of 1.4% per year during 2013 to 2017. Among adolescents and young adults aged 15 to 39 years, cancer incidence rates increased an average of 0.9% per year during 2012 to 2016, and cancer death rates decreased an average of 1.0% per year during 2013 to 2017. Conclusions: Although overall cancer death rates continue to decline, incidence rates are leveling off among males and are increasing slightly among females. These trends reflect population changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are found early. Population-based cancer incidence and mortality data can be used to inform efforts to decrease the cancer burden in the United States and regularly monitor progress toward goals.
Article
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non‐Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre‐diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow‐up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T‐NHL), B cell NHL (B‐NHL) and three individual B‐NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B‐NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0, and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T‐NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B‐NHLs other than CLL/SLL and for VLCSFA and MUFA with T‐NHL suggest an influence of fatty acid metabolism on lymphomagenesis. This article is protected by copyright. All rights reserved.
Article
Inflammation is considered an enabling feature of cancer. Besides the persistence of inflammatory stimuli, also defective mechanisms of resolution can lead to chronic inflammation. Inflammation resolution is an active process controlled by lipidic specialized pro-resolving mediators (SPMs), derived from ω-3 or ω-6 essential polyunsaturated fatty acids (PUFA) through the activity of lipoxygenases (ALOX5 and 15). Thus, a lack or defect in resolution mechanisms may affect cancer development and progression by prolonging inflammation. Components of pro-resolving pathways (PUFA, enzymes, or SPMs) have been reported to modulate various cancer features by affecting both cancer cells and cancer-associated stroma. Here, we will review the most important mechanisms by which SPMs, ω-3/6 PUFA, and ALOXs affect cancer biology, paying particular attention to their role in the inhibition of inflammation and angiogenesis, two of the most important hallmarks of cancer. The collection of these results may suggest novel perspectives in cancer management based on the modulation of lipid metabolism and the production of SPMs.
Article
We examined the association between fruit/vegetable consumption and the risk of hematological malignancies in cohort studies (end of search: August 31, 2016). Total fruit consumption was not associated with the risk of non-Hodgkin lymphoma (NHL) (RR = 1.03, 95% CI: 0.92-1.16, I(2) = 12.1%, n = 7), acute myeloid leukemia (RR = 1.23, 95% CI: 0.94-1.61, I(2) = 0%, n = 3), multiple myeloma (MM; RR = 1.05, 95% CI: 0.72-1.55, I(2) = 60.0%, n = 4), and Hodgkin lymphoma. However, citrus fruit consumption was associated with reduced NHL risk (RR = 0.85, 95% CI: 0.73-1.00, p = .044, I(2) = 0%, n = 6). Vegetable intake was marginally associated with reduced NHL risk (RR = 0.89, 95% CI: 0.79-1.00, p = .056, I(2) = 16.2%, n = 7), but not with acute myeloid leukemia, multiple myeloma, and Hodgkin lymphoma risk. Nevertheless, NHL risk was inversely associated with cruciferous vegetable consumption (RR = 0.84, 95% CI: 0.71-1.00, p = .047, I(2) = 0%, n = 3). Notably, combined fruit/vegetable consumption was associated with decreased NHL risk (RR = 0.79, 95% CI: 0.65-0.96, I(2) = 11.2%, n = 3). This meta-analysis reveals possible protective effects; however, confounding and reporting bias could have affected the results.
Article
Background: Dietary fat intake may contribute to non-Hodgkin lymphoma (NHL) pathogenesis by influencing carcinogen exposure or through immune modulation. Objective: We aimed to evaluate NHL risk associated with total and specific dietary fat intake. Design: We evaluated associations within the Nurses’ Health Study (NHS) (n = 88,598) and the Health Professionals Follow-Up Study (HPFS) (n = 47,531) using repeated validated dietary assessments. We confirmed 1802 incident NHL diagnoses through 2010. Using multivariable Cox proportional hazards models, we estimated hazard ratios (HRs) for all NHL and common subtypes associated with a 1-SD increase in cumulative mean intakes of total, animal, saturated, trans, and vegetable fats and marine fatty acids. We pooled sex-specific HRs using random-effects meta-analysis. Results: Over 24–30 y of follow-up, neither total nor specific dietary fats were significantly associated with NHL risk overall. Higher total, animal, and saturated fat intakes were positively associated with the risk of the chronic lymphocytic leukemia/small lymphocytic lymphoma subtype among women only (253 cases; P-trend ≤ 0.05), driven by strong associations during 1980–1994. From baseline through 1994, among women and men combined, total fat intake was borderline-significantly positively associated with NHL overall (pooled HR per SD: 1.13; 95% CI: 0.99, 1.29) and was significantly associated with diffuse large B cell lymphoma (pooled HR per SD: 1.47; 95% CI: 1.06, 2.05), with similar trends for animal and saturated fat intake. For women only, trans fat was significantly positively associated with all NHL. In contrast, during 1994–2010, there was little evidence for associations of dietary fat intake with NHL overall or by subtype. Conclusion: Previous observations of an increased risk of NHL associated with intakes of total, animal, saturated, and trans fat with 14 y of follow-up did not persist with longer follow-up.
Article
The authors compared the ability of the National Death Index and the Equifax Nationwide Death Search to ascertain deaths of participants in the Nurses' Health Study. Each service was sent information on 197 participants aged 60–68 years in 1989 whose deaths were reported by kin or postal authorities and 1,997 participants of the same age who were known to be alive. Neither service was aware of the authors' information regarding participants' vital status. The sensitivity of the National Death Index was 98 percent and that of Equifax was 79 percent. Sensitivity was similar for women aged 65–68 years; however, for women aged 61–64 years, the sensitivity of the National Death Index was 97.7 percent compared with 60.2 percent for Equifax. The specificity of both services was approximately 100 percent. The contrast between the sources of these databases and the matching algorithms they employ has implications for researchers and for those planning health data systems.
Article
Objective: The aim of this study was to assess the association between polyunsaturated fatty acids (PUFAs) and inflammatory biomarkers among patients in secondary prevention of cardiovascular disease (CVD). Methods: In this cross-sectional substudy from BALANCE Program Trial, we have collected data from 364 patients with established CVD. Twenty-four-hour dietary recalls and plasma FA concentrations were analyzed to estimate the FA intake. Inflammatory biomarkers measurement consisted of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, C-reactive protein, adiponectin, and tumor necrosis factor-α. After log-transformation of inflammatory biomarkers, multivariate-adjusted general linear model was used to examine the effect of FA intake. The association was adjusted for body mass index, waist circumference, energy, smoking status, age, total cholesterol, low-density lipoprotein cholesterol, physical activity, and calcium channel blockers. Results: PUFAs were inversely associated with C-reactive protein levels (P = 0.006) and with IL-1 β. The increase of 1 g/1000 kcal in PUFAs, omega-3, and omega-6 reduces, on average, 6%, 48%, and 8% respectively, the mean concentration of IL-1 β. Conclusion: Omega-3 and omega-6 FA intakes are inversely associated with inflammatory biomarkers among CVD patients. Additional studies on omega-3 and omega-6 intake in relation to inflammatory biomarkers in patients in secondary prevention of CVD are needed, particularly regarding dietary patterns that are rich in some sources of PUFA.
Conference Paper
A revision of the nearly 8 year old WHO classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations and therapeutic strategies for the lymphoid neoplasms.
Article
A population-based case-control study (601 cases and 717 controls) was conducted in 1995–2001 among Connecticut women to evaluate the relation between diet and nutrient intakes and the risk of non-Hodgkin’s lymphoma (NHL). When the highest quartile of intake was compared with the lowest, the authors found an increased risk of NHL associated with animal protein (odds ratio = 1.7, 95% confidence interval: 1.2, 2.4) and saturated fat (odds ratio = 1.9, 95% confidence interval: 1.1, 2.3) but a reduced risk for polyunsaturated fat (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9) and no relation for vegetable protein and monounsaturated fat. An increased risk was also observed for higher intakes of retinol, eggs, and dairy products. On the other hand, a reduced risk was found for higher intakes of dietary fiber and for several fruit and vegetable items. Risk of NHL associated with diet and nutrient intakes appeared to vary based on NHL subtype. An association between dietary intake and NHL risk is biologically plausible because diets high in protein and fat may lead to altered immunocompetence, resulting in an increased risk of NHL. The antioxidant or inhibiting nitrosation reaction properties of vegetables and fruits may result in a reduced risk. Further investigation of the role of dietary intakes on the risk of NHL is warranted. case-control studies; diet; dietary fats; lymphoma, non-Hodgkin; proteins; risk factors; women Abbreviations: CI, confidence interval; NHL, non-Hodgkin’s lymphoma; OR, odds ratio; RR, relative risk.
Article
Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor peroxisome proliferator activated receptor γ and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked, although the full extent of this is not yet elucidated. Animal experiments demonstrate benefit from marine n-3 fatty acids in models of rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in RA demonstrate benefit, but clinical trials of fish oil in IBD and asthma are inconsistent with no overall clear evidence of efficacy. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance."
Article
A generalized (extreme Studentized deviate) ESD many-outlier procedure is given for detecting from 1 to k outliers in a data set. This procedure has an advantage over the original ESD many-outlier procedure (Rosner 1975) in that it controls the type I error both under the hypothesis of no outliers and under the alternative hypotheses of 1, 2, …. k-l outliers. A method is given for approximating percentiles for this procedure based on the t distribution. This method is shown to be adequately accurate using Monte Carlo simulation, for detecting up to 10 outliers in samples as small as 25. Tables are given for implementing this method for n = 25(1)50(10)100(50)500; k = 10, α = .05, .Ol, .005.
Article
Composition of dietary fatty acid intake, which influences cytokine production, may contribute to the development of non-Hodgkin's lymphoma (NHL). Serum lipid levels may serve as biomarkers of inflammation associated with NHL risk. We conducted a case-control analysis (275 cases and 549 controls) nested within the Multiethnic Cohort Study (whites, Japanese Americans, Latinos, African Americans, and Native Hawaiians) to examine the association of prediagnostic, erythrocyte membrane phospholipid fatty acid composition, and serum cholesterol and triglyceride (TG) concentrations with the risk of NHL. Conditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) by tertiles of biomarker concentrations. Higher total saturated fatty acids (SFA) were associated with an increase in NHL risk (OR(T3 vs. T1) = 1.57 [95 % CI: 1.03-2.39]; p (trend) = 0.01), whereas no associations were detected for total n-3 or n-6 polyunsaturated fatty acids. Inverse associations were observed for total cholesterol (TC; OR (T3 vs. T1) = 0.51 [95 % CI: 0.35-0.74]; p ( trend ) < 0.0001) and high-density lipoprotein cholesterol (HDL-C; OR (T3 vs. T1) = 0.47 [95 % CI: 0.31-0.71]; p ( trend ) = 0.0001) but not for low-density lipoprotein cholesterol or TG. Adjustment for the use of lipid-lowering medication did not modify the results substantially. This prospective biomarker investigation offers supportive evidence for an adverse effect of higher erythrocyte membrane SFA levels on NHL risk, but preclinical effects cannot be excluded. Inverse relations between prediagnostic, circulating TC and HDL-C and NHL risk may be due to reverse causation or a result of protective actions of these lipids and lipoproteins.
Article
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are precursors of potent lipid mediators, termed eicosanoids, which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 PUFAs (e.g., arachidonic acid) have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFAs [e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have anti-inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived eicosanoids. While the typical Western diet has a much greater ratio of n-6 PUFAs compared with n-3 PUFAs, research has shown that by increasing the ratio of n-3 to n-6 fatty acids in the diet, and consequently favoring the production of EPA in the body, or by increasing the dietary intake of EPA and DHA through consumption of fatty fish or fish-oil supplements, reductions may be achieved in the incidence of many chronic diseases that involve inflammatory processes; most notably, these include cardiovascular diseases, inflammatory bowel disease (IBD), cancer, and rheumatoid arthritis, but psychiatric and neurodegenerative illnesses are other examples.
Article
The role of various life style factors, including dietary habits, in the etiology of non-Hodgkin's lymphoma was investigated using data from a case-control study conducted in the northeastern part of Italy. This study was done on 208 histologically confirmed non-Hodgkin's lymphomas and 401 control subjects who were in the hospital for acute, nonimmunologic, or neoplastic conditions. Dietary histories concerned the frequency of consumption per week of alcohol, beverages that contain methylxanthine, and 14 select food items or groups of foods (including major sources of proteins, fat, fibers, and vitamin A in the Italian diet). The consumption of milk, liver, butter, oil (chiefly polyunsaturated oils), coffee, tea, and cola was positively related with non-Hodgkin's lymphoma risk. the consumption of whole-grain bread and pasta showed a protective effect. When a logistic model was fitted that included the aforementioned food items in addition to major nondietary covariates, all of the foods, except liver and beverages that contain methylxanthine, remained significant. Interestingly, these associations are in agreement with the positive correlation that is emerging internationally between the consumption of fat and proteins and non-Hodgkin's lymphoma.
Article
We describe the use of cubic splines in regression models to represent the relationship between the response variable and a vector of covariates. This simple method can help prevent the problems that result from inappropriate linearity assumptions. We compare restricted cubic spline regression to non-parametric procedures for characterizing the relationship between age and survival in the Stanford Heart Transplant data. We also provide an illustrative example in cancer therapeutics.
Article
To test whether high dietary intakes of fat, protein, and milk are associated with the development of non-Hodgkin lymphoma in older women. Prospective cohort study with a 7-year follow-up period. General community. Sample of 35 156 Iowa women aged 55 to 69 years with no prior history of cancer who returned the 1986 baseline questionnaire. Non-Hodgkin lymphoma (104 incident cases). After controlling for age, marital status, residence, total energy intake, and transfusion history, the relative risks (RRs) for the highest tertile of intake compared with the lowest were 2.00 (95% confidence interval [CI], 1.21-3.30; P for trend = .01) for animal fat, 1.69 (95% CI, 1.07-2.67; P for trend = .02) for saturated fat, and 1.90 (95% CI, 1.18-3.04; P for trend = .01) for monounsaturated fat, and there was no association with vegetable fat or polyunsaturated fat. Greater intake of animal protein (RR = 1.52; 95% CI, 0.94-2.44; P for trend = .08), but not vegetable protein, was associated with elevated risk, and this was mainly explained by greater consumption of red meat (RR = 1.98; 95% CI, 1.13-3.47; P for trend = .02) and hamburger in particular (RR = 2.35; 95% CI, 1.23-4.48; P for trend = .02). Milk and dairy product consumption were not associated with elevated risk. There was also a decreased risk of non-Hodgkin lymphoma with greater consumption of fruits (RR = 0.64; 95% CI, 0.40-1.05; P for trend = .07). A high-meat diet and a high intake of fat from animal sources is associated with an increased risk of non-Hodgkin lymphoma in older women.
Article
To review the various biomarkers of dietary intakes of fatty adds in human populations, their measurement, limitations and analytical considerations. Review of the literature. Although there is no good biomarker of intake of total fat, a number of alternatives exist for assessing the intakes of exogenously produced fatty acids that are consumed. Adipose tissue, erythrocyte membrane concentrations and serum or plasma levels can reflect prior intakes over the past few hours to the past few years. The concentrations of individual fatty acids in these media generally reflect relative levels, and are influenced by a number of factors. Although relatively expensive to analyse, a single analysis by gas chromatography or high-performance liquid chromatography provides information on multiple fatty acids, and is superior to attempting to measure specific fatty acids using traditional dietary assessment methods. Biomarkers of fatty acids that reflect long-term intake are available for nutritional epidemiology purposes. Analytical methods have become very accurate and able to detect and quantify smaller families, such as trans-fatty acids.
Article
Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial effects of n-3 fatty acids. We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 alpha-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPA+DHA) intake and tumor necrosis factor receptors among participants with low intake of n-6 but a strong inverse association among those with high n-6 intake (P=0.04 and 0.002 for interaction of n-3 with n-6 on sTNF-R1 and sTNF-R2, respectively). These results suggest that n-6 fatty acids do not inhibit the antiinflammatory effects of n-3 fatty acids and that the combination of both types of fatty acids is associated with the lowest levels of inflammation. The inhibition of inflammatory cytokines may be one possible mechanism for the observed beneficial effects of these fatty acids on chronic inflammatory-related diseases.
Article
We evaluated the hypothesis that intake of (n-3) fatty acids is inversely associated with biomarkers of inflammation and endothelial activation. We conducted a cross-sectional study of 727 women from the Nurses' Health Study I cohort, aged 43-69 y, apparently healthy at time of a blood draw in 1990. Dietary intake was assessed by a validated FFQ in 1986 and 1990. C-reactive protein (CRP) levels were 29% lower among those in the highest quintile of total (n-3) fatty acids, compared with the lowest quintile; interleukin-6 (IL-6) levels were 23% lower, E-selectin levels 10% lower, soluble intracellular adhesion molecule (sICAM-1) levels 7% lower, and soluble vascular adhesion molecule (sVCAM-1) levels 8% lower. The intake of alpha-linolenic acid was inversely related to plasma concentrations of CRP (beta = -0.55, P = 0.02), Il-6 (beta = -0.36, P = 0.01), and E-selectin (beta = -0.24, P = 0.008) after controlling for age, BMI, physical activity, smoking status, alcohol consumption, and intake of linoleic acid (n-6) and saturated fat. Long-chain (n-3) fatty acids (eicosapentaenoic and docosahexaenoic) were inversely related to sICAM-1 (beta = -0.11, P = 0.03) and sVCAM-1 (beta = -0.17, P = 0.003). Total (n-3) fatty acids had an inverse relation with CRP (beta = -0.44, P = 0.007), IL-6 (beta = -0.26, P = 0.009), E-selectin (beta = -0.17, P = 0.004), sICAM-1 (beta = -0.07, P = 0.02), and sVCAM-1 (beta = -0.10, P = 0.004). These associations were not modified by intake of vitamin E, dietary fiber, trans fatty acids, or by the use of postmenopausal hormone therapy. In conclusion, this study suggests that dietary (n-3) fatty acids are associated with levels of these biomarkers reflecting lower levels of inflammation and endothelial activation, which might explain in part the effect of these fatty acids in preventing cardiovascular disease.
Article
Erythrocyte fatty acids may be superior to plasma fatty acids for reflecting long-term fatty acid intake because of less sensitivity to recent intake and a slower turnover rate. The objective was to compare the fatty acid content of erythrocytes with that of plasma with respect to their abilities to reflect usual fatty acid intake. Fatty acids in plasma and erythrocytes were measured by capillary gas-liquid chromatography in 306 US women aged 43-69 y. Fatty acid intake was assessed with a food-frequency questionnaire, which was validated for measuring intakes of various fatty acids. Docosahexaenoic acid (DHA, 22:6n-3) in erythrocytes and plasma provided the strongest correlations with its intake, but erythrocyte DHA concentrations [Spearman's partial correlation coefficient (r(s))=0.56] were better than plasma DHA concentrations (r(s)=0.48) as a biomarker. Total trans fatty acids (r(s)=0.43) and total 18:1 trans isomers (r(s)=0.42) in erythrocytes were also more strongly correlated with intake than were those in plasma (r(s)=0.30 and r(s)=0.29, respectively). Moderate correlations were observed for linoleic acid (18:2n-6; erythrocytes, r(s)=0.24; plasma, r(s)=0.25), alpha-linolenic acid (18:3n-3; erythrocytes, r(s)=0.18; plasma, r(s)=0.23), and eicosapentaenoic acid (20:5 n-3; erythrocytes, r(s)=0.38; plasma, r(s)=0.21). For polyunsaturated and trans fatty acids, correlations between intakes and biomarkers improved moderately when average intakes over previous years were used. Erythrocyte n-3 fatty acids of marine origin and trans fatty acid content are suitable biomarkers for long-term intake.
Article
Multiple testing is a challenging issue in genetic association studies using large numbers of single nucleotide polymorphism (SNP) markers, many of which exhibit linkage disequilibrium (LD). Failure to adjust for multiple testing appropriately may produce excessive false positives or overlook true positive signals. The Bonferroni method of adjusting for multiple comparisons is easy to compute, but is well known to be conservative in the presence of LD. On the other hand, permutation-based corrections can correctly account for LD among SNPs, but are computationally intensive. In this work, we propose a new multiple testing correction method for association studies using SNP markers. We show that it is simple, fast and more accurate than the recently developed methods and is comparable to permutation-based corrections using both simulated and real data. We also demonstrate how it might be used in whole-genome association studies to control type I error. The efficiency and accuracy of the proposed method make it an attractive choice for multiple testing adjustment when there is high intermarker LD in the SNP data set.