Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study.

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs.-prevaccine and vaccinated-vs.-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs.-prevaccine than in the vaccinated-vs.-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence.

Comparison of cohort and nested case-control designs for estimating the effect of time-varying drug exposure on the risk of adverse event in the presence of ties.

Cohort and nested case-control (NCC) designs are frequently used in pharmacoepidemiology to assess the associations of drug exposure that can vary over time with the risk of an adverse event. Although it is typically expected that estimates from NCC analyses are similar to those from the full cohort analysis, with moderate loss of precision, only few studies have actually compared their respective performance for estimating the effects of time-varying exposures (TVE). We used simulations to compare the properties of the resulting estimators of these designs for both time-invariant exposure and TVE. We varied exposure prevalence, proportion of subjects experiencing the event, hazard ratio, and control-to-case ratio and considered matching on confounders. Using both designs, we also estimated the real-world associations of time-invariant ever use of menopausal hormone therapy (MHT) at baseline and updated, time-varying MHT use with breast cancer incidence. In all simulated scenarios, the cohort-based estimates had small relative bias and greater precision than the NCC design. NCC estimates displayed bias to the null that decreased with a greater number of controls per case. This bias markedly increased with higher proportion of events. Bias was seen with Breslow's and Efron's approximations for handling tied event times but was greatly reduced with the exact method or when NCC analyses were matched on confounders. When analyzing the MHT-breast cancer association, differences between the two designs were consistent with simulated data. Once ties were taken correctly into account, NCC estimates were very similar to those of the full cohort analysis.

Contact patterns and HPV-genotype interactions yield heterogeneous HPV-vaccine impacts depending on sexual behaviors: An individual-based model.

Human papillomaviruses are common sexually transmitted infections, caused by a large diversity of genotypes. In the context of vaccination against a subgroup of genotypes, better understanding the role of genotype interactions and human sexual behavior on genotype dynamics is essential. Herein, we present an individual-based model that integrates realistic heterosexual partnership behaviors and simulates interactions between vaccine and non-vaccine genotypes. Genotype interactions were considered, assuming a previous vaccine-genotype infection shortened (competition) or extended (synergy) the duration of a secondary non-vaccine-genotype infection. Sexual behavior determined papillomavirus acquisition and transmission: only 19.5% of active individuals at most 1 partner r during the year, but > 80% of those with ≥ 2 partners, were infected before vaccine introduction. The pre-vaccination situation was consistent with all genotype interaction scenarios. These genotype interactions, despite being undetectable during the pre-vaccination era, markedly impacted genotype prevalence after vaccination started, with a significant increase/decrease of non-vaccine genotypes prevalence for respectively competitive/synergistic interactions. These prevalence changes were more pronounced in individuals with ≤ 3 partners per year (up to 30% of prevalence modification assuming 65% vaccine coverage) but barely visible for individuals with > 3 partners per year (at most 0.30%). Results suggest the presence of genotype interaction, which is consistent with the pre-vaccine situation, may impact the dynamics of non-vaccine genotypes, particularly in less active individuals.

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

BACKGROUND: Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. METHODS/DESIGN: This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. DISCUSSION: This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02904811 . Registered on September 14, 2016. World Health Organisation International Clinical Trials Registry, NCT02904811. AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1.

A Cohort Study of Adolescent and Midlife Diet and Pancreatic Cancer Risk in the NIH-AARP Diet and Health Study.

Given the long latency period of pancreatic cancer, exploring the influence of early and midlife exposures will further advance our understanding of the disease. We assessed associations between diet and pancreatic cancer incidence in the National Institutes of Health (NIH)-AARP (formerly American Association of Retired Persons) Diet and Health Study. In 1996, a total of 303,094 participants completed 2 food frequency questionnaires that assessed diet at ages 12-13 years and 10 years previously. We used Cox proportional hazards regression to estimate adjusted hazard ratios and 95% confidence intervals. Through the end of 2006, a total of 1,322 pancreatic cancer cases occurred (average follow up time = 10.1 years). When comparing the highest tertiles with the lowest, carbohydrate intake during adolescence (hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.76, 0.99), but not 10 years before baseline, was inversely associated with pancreatic cancer risk. Total fat intake 10 years before baseline was significantly associated with increased risk (HR = 1.17, 95% CI: 1.02, 1.34), while risk was higher for high fat intake during both adolescence and midlife. Calcium intake 10 years before baseline was associated with reduced risk (HR = 0.87, 95% CI: 0.76, 0.99), as was a change from low intake in adolescence to high intake in midlife (HR = 0.71, 95% CI: 0.54, 0.93). Our study found a number of dietary factors present during adolescence and midlife to be associated with pancreatic cancer.

Comparison of methods for estimating the attributable risk in the context of survival analysis.

BACKGROUND: The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. METHODS: Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points. RESULTS: Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort. CONCLUSION: In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears appropriate.

Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies.

BACKGROUND: Mucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences. METHODS: We performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference. RESULTS: Twenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]). CONCLUSIONS: Our results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer.

The performance of functional methods for correcting non-Gaussian measurement error within Poisson regression: corrected excess risk of lung cancer mortality in relation to radon exposure among French uranium miners.

A broad variety of methods for measurement error (ME) correction have been developed, but these methods have rarely been applied possibly because their ability to correct ME is poorly understood. We carried out a simulation study to assess the performance of three error-correction methods: two variants of regression calibration (the substitution method and the estimation calibration method) and the simulation extrapolation (SIMEX) method. Features of the simulated cohorts were borrowed from the French Uranium Miners' Cohort in which exposure to radon had been documented from 1946 to 1999. In the absence of ME correction, we observed a severe attenuation of the true effect of radon exposure, with a negative relative bias of the order of 60% on the excess relative risk of lung cancer death. In the main scenario considered, that is, when ME characteristics previously determined as most plausible from the French Uranium Miners' Cohort were used both to generate exposure data and to correct for ME at the analysis stage, all three error-correction methods showed a noticeable but partial reduction of the attenuation bias, with a slight advantage for the SIMEX method. However, the performance of the three correction methods highly depended on the accurate determination of the characteristics of ME. In particular, we encountered severe overestimation in some scenarios with the SIMEX method, and we observed lack of correction with the three methods in some other scenarios. For illustration, we also applied and compared the proposed methods on the real data set from the French Uranium Miners' Cohort study.

Impact of measurement error in radon exposure on the estimated excess relative risk of lung cancer death in a simulated study based on the French Uranium Miners' Cohort.

Measurement error (ME) can lead to bias in the analysis of epidemiologic studies. Here a simulation study is described that is based on data from the French Uranium Miners' Cohort and that was conducted to assess the effect of ME on the estimated excess relative risk (ERR) of lung cancer death associated with radon exposure. Starting from a scenario without any ME, data were generated containing successively Berkson or classical ME depending on time periods, to reflect changes in the measurement of exposure to radon ((222)Rn) and its decay products over time in this cohort. Results indicate that ME attenuated the level of association with radon exposure, with a negative bias percentage on the order of 60% on the ERR estimate. Sensitivity analyses showed the consequences of specific ME characteristics (type, size, structure, and distribution) on the ERR estimates. In the future, it appears important to correct for ME upon analyzing cohorts such as this one to decrease bias in estimates of the ERR of adverse events associated with exposure to ionizing radiation.

Adolescent and mid-life diet: risk of colorectal cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Colorectal cancer has a natural history of several decades; therefore, the diet consumed decades before diagnosis may aid in understanding this malignancy. OBJECTIVE: The objective was to investigate diet during adolescence and 10 y before baseline (ages 40-61 y) in relation to colorectal cancer. DESIGN: Participants in the NIH-AARP Diet and Health Study (n = 292,797) completed a 124-item food-frequency questionnaire (FFQ) about diet in the past 12 mo and two 37-item FFQs about diet at ages 12-13 y and 10 y previously. Cox regression was used to estimate multivariate HRs and 95% CIs for colon (n = 2794) and rectal (n = 979) cancers within quintiles of exposures. RESULTS: Colon cancer risk was lower in the highest than in the lowest quintile of vitamin A (HR: 0.82; 95% CI: 0.72, 0.92) and vegetable (HR: 0.81, 0.70, 0.92) intakes during adolescence. Those in the highest intake category 10 y previously for calcium (HR: 0.83; 95% CI: 0.73, 0.94), vitamin A (HR: 0.81; 95% CI: 0.71, 0.92), vitamin C (HR: 0.83; 95% CI: 0.72, 0.95), fruit (HR: 0.84; 95% CI: 0.73, 0.97), and milk (HR: 0.78; 95% CI: 0.67, 0.90) had a lower risk of colon cancer, but a higher risk was observed for total fat (HR: 1.15; 95% CI: 1.01, 1.30), red meat (HR: 1.31; 95% CI: 1.12, 1.53), and processed meat (HR: 1.24; 95% CI: 1.06, 1.45). For rectal cancer, milk was inversely associated (HR: 0.75; 95% CI: 0.58, 0.96) with risk. CONCLUSION: Adolescent and midlife diet may play a role in colorectal carcinogenesis.

Correlation between serum phospholipid fatty acids and dietary intakes assessed a few years earlier.

The fatty acid composition of serum phospholipids has been shown to reflect dietary intakes in the previous weeks or months. However, how serum phospholipids relate to fatty acid intakes over a few years has hardly been examined. We designed a cross-sectional study within the E3N cohort, the French component of the European Prospective Investigation into Cancer and Nutrition in which female participants completed a 208-item diet history questionnaire in 1993-1995 and provided blood samples in 1995-1998. The study included 1,114 women who were free of cancer at the time of blood collection. Serum phospholipid fatty acid composition was assessed by capillary gas chromatography. Partial Spearman correlations adjusted for age and body mass index showed weak to moderate, although statistically significant, positive associations between dietary and serum oleic, linoleic, arachidonic, eicosapentaenoic, and docosahexaenoic acids. Moreover, serum oleic acid was directly associated with olive oil, linoleic acid with sunflower oil, pentadecanoic acid with dairy products, long-chain n-3 fatty acids with fatty fish, and trans-monounsaturated fatty acids with manufactured foods. In conclusion, serum phospholipid pentadecanoic acid, oleic, trans-monounsaturated, and polyunsaturated fatty acids are suitable biomarkers for usual dietary intakes, although the association may weaken as the time lag between dietary assessment and blood collection increases.

Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study.

BACKGROUND: Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. METHODS: We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995-1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. RESULTS: Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; P(trend) = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; P(trend) < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; P(trend) = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; P(trend) < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). CONCLUSION: In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.

Ductal lavage in women from BRCA1/2 families: is there a future for ductal lavage in women at increased genetic risk of breast cancer?

PURPOSE: Ductal lavage has been used for risk stratification and biomarker development and to identify intermediate endpoints for risk-reducing intervention trials. Little is known about patient characteristics associated with obtaining nipple aspirate fluid (NAF) and adequate cell counts (> or =10 cells) in ductal lavage specimens from BRCA mutation carriers. METHODS: We evaluated patient characteristics associated with obtaining NAF and adequate cell counts in ductal lavage specimens from the largest cohort of women from BRCA families yet studied (BRCA1/2 = 146, mutation-negative = 23, untested = 2). Fisher's exact test was used to evaluate categorical variables; Wilcoxon nonparametric test was used to evaluate continuous variables associated with NAF or ductal lavage cell count adequacy. Logistic regression was used to identify independent correlates of NAF and ductal lavage cell count adequacy. RESULTS: From 171 women, 45 (26%) women had NAF and 70 (41%) women had ductal lavage samples with > or =10 cells. Postmenopausal women with intact ovaries compared with premenopausal women [odds ratio (OR), 4.8; P = 0.03] and women without a prior breast cancer history (OR, 5.2; P = 0.04) had an increased likelihood of yielding NAF. Having breast-fed (OR, 3.4; P = 0.001), the presence of NAF before ductal lavage (OR, 3.2; P = 0.003), and being premenopausal (OR, 3.0; P = 0.003) increased the likelihood of ductal lavage cell count adequacy. In known BRCA1/2 mutation carriers, only breast-feeding (OR, 2.5; P = 0.01) and the presence of NAF (OR, 3.0; P = 0.01) were independent correlates of ductal lavage cell count adequacy. CONCLUSIONS: Ductal lavage is unlikely to be useful in breast cancer screening among BRCA1/2 mutation carriers because the procedure fails to yield adequate specimens sufficient for reliable cytologic diagnosis or to support translational research activities.

Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study.

The epidemiologic evidence for the role of alcohol use in pancreatic cancer development is equivocal. The authors prospectively examined the relation between alcohol use and risk of pancreatic cancer among 470,681 participants who were aged 50-71 years in 1995-1996 in the US National Institutes of Health-AARP Diet and Health Study. The authors identified 1,149 eligible exocrine pancreatic cancer cases through December 2003. Multivariate Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals with the referent group being light drinkers (<1 drink/day). The relative risks of developing pancreatic cancer were 1.45 (95% confidence interval (CI): 1.17, 1.80; P(trend) = 0.002) for heavy total alcohol use (>or=3 drinks/day, approximately 40 g of alcohol/day) and 1.62 (95% CI: 1.24, 2.10; P(trend) = 0.001) for heavy liquor use, compared with the respective referent group. The increased risk with heavy total alcohol use was seen in never smokers (relative risk = 1.35, 95% CI: 0.79, 2.30) and participants who quit smoking 10 or more years ago before baseline (relative risk = 1.41, 95% CI: 1.01, 2.00). These findings suggest a moderately increased pancreatic cancer risk with heavy alcohol use, particularly liquor; however, residual confounding by cigarette smoking cannot be completely excluded.

Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.

Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.

Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer. OBJECTIVE: We aimed to investigate the association between fat consumption and breast cancer. DESIGN: We prospectively investigated fat consumption in a large (n = 319,826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer. RESULTS: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable]. CONCLUSIONS: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy.

Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3N-EPIC Study.

The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study (1989-2002), the French component of the European Prospective Investigation into Cancer and Nutrition. During an average of 7 years of follow-up, 363 cases of incident invasive breast cancer were documented among 19,934 women who, at baseline (1995-1998), had completed a diet history questionnaire and provided serum samples. Controls were randomly matched to cases by age, menopausal status at blood collection, fasting status at blood collection, date, and collection center. Serum phospholipid fatty acid composition was assessed by gas chromatography. Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression. An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid (highest quintile vs. lowest: odds ratio = 1.75, 95% confidence interval: 1.08, 2.83; p-trend = 0.018). cis-Monounsaturated fatty acids were unrelated to breast cancer risk. A high serum level of trans-monounsaturated fatty acids, presumably reflecting a high intake of industrially processed foods, is probably one factor contributing to increased risk of invasive breast cancer in women.

The role of dietary measurement error in investigating the hypothesized link between dietary fat intake and breast cancer--a story with twists and turns.

The association between dietary fat and breast cancer is one of the most controversial hypotheses in nutritional epidemiology. In this editorial, the authors review the evidence from animal and human studies, including international correlation, case-control, cohort studies, intervention trials, and studies comparing dietary assessment instruments. The authors emphasize the importance of the role played by measurement error arising from assessing dietary habits using self-reported questionnaires, as it can distort estimated associations, not necessarily towards the absence of an association. They describe the twists and turns of the dietary fat and breast cancer debate that have revolved around this issue.

Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study.

BACKGROUND: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality. METHODS: Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27,799 deaths were documented. In the first 5 years of follow-up, 5,985 cancer deaths and 3,451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern (components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat-saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models. RESULTS: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 (95% CI, 0.76-0.83), 0.78 (95% CI, 0.69-0.87), and 0.83 (95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P = .04 and P < .001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged. CONCLUSION: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population.