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BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with

BackgroundLittle is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients.MethodsUsing self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history.ResultsOf 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer–specific mortality.ConclusionsRegular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.

BACKGROUND Diet quality scores (DQSs) are frequently used to study diet-disease relationships but the validity of these scores derived from food frequency questionnaires (FFQs) has rarely been evaluated. OBJECTIVE To evaluate the validity and reproducibility of six commonly used DQSs derived from the FFQ, including the Alternate Healthy Eating Index-2010 (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH) score, alternative Mediterranean Diet score (AMED), and three plant-based diet indices (overall, healthful, and unhealthful). DESIGN This analysis included 1,394 participants from the Men's (n = 652) and Women's (n = 742) Lifestyle Validation Studies. Participants completed a 152-item FFQ at the beginning of the study and one year later, and completed two weighed 7-day dietary records (7DDRs) and donated two blood samples six-month apart between FFQ assessments. The reproducibility of the FFQs was evaluated by rank intraclass correlation coefficients (ICC). The validity was assessed by comparing FFQ-derived DQSs to those from the average of two 7DDRs using Spearman rank correlation coefficients deattenuated for random measurement error in the 7DDRs (rs). Further, we calculated the correlations between DQSs and plasma biomarkers of diet including fatty acids, folate, carotenoids, retinol, and alpha-and gamma-tocopherol. RESULTS Six FFQ derived DQSs demonstrated moderate to high reproducibility (energy-adjusted ICCs = 0.61 to 0.84) and validity (energy-adjusted, deattenuated rs = 0.56 to 0.80) in both men and women. We consistently observed expected correlations between FFQ derived DQSs with plasma fatty acids, including long chain N-3 and trans fatty acids, most carotenoids, and gamma-tocopherol (rs>0.2). CONCLUSIONS Our study demonstrates the validity of the FFQ to evaluate overall diet quality using six commonly used DQSs. In addition, these DQSs have qualitatively demonstrated biological relevance as indicated by their correlations with circulating biomarkers.

Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991–2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). Conclusion Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

Background In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. Methods Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). Results In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. Conclusions We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

Background Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine—a nicotine metabolite and biomarker of recent tobacco exposure—provides additional information on lung cancer risk. Methods The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32–1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68–0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64–0.68) (P = 1.5x10–9). Conclusions Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone. © The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer.Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided.Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status.001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04).We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.

Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study.

BACKGROUND: More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consumption and to assess whether non-dietary risk factors modify the relation. METHODS: We combined the primary data from eight prospective cohort studies from North America and Western Europe with at least 200 incident breast cancer cases, assessment of usual food and nutrient intakes, and a validation study of the dietary assessment instrument. The pooled database included 351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow-up. RESULTS: We found no significant association between intakes of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast cancer risk. Categorical analyses suggested a J-shaped association for egg consumption where, compared to women who did not eat eggs, breast cancer risk was slightly decreased among women who consumed < 2 eggs per week but slightly increased among women who consumed > or = 1 egg per day. CONCLUSIONS: We found no significant associations between intake of meat or dairy products and risk of breast cancer. An inconsistent relation between egg consumption and risk of breast cancer merits further investigation.