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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

Optimizing vitamin D status through the use of supplementation and/or judicious sun exposure has been proposed as a BC risk reduction strategy. This simple and non-invasive approach to BC prevention is extremely appealing given that vitamin D concentrations in circulation are low in many individuals around the world. However, an Institute of Medicine (IOM) report found the evidence on vitamin D and breast cancer to be inconsistent. To clarify the relationship between vitamin D and breast cancer, data was pooled on approximately 25,000 women from 17 prospective cohorts worldwide. The association between pre-diagnostic circulating 25(OH)D levels, the accepted measure of vitamin D status, and breast cancer incidence was examined. For five cohorts, vitamin D status was assessed at a central laboratory (Heartland Assays, Inc.) using a direct, competitive chemiluminescence immunoassay that measures 25(OH)D2 and 25(OH)D3 equivalently. In 12 cohorts with previously measured 25(OH)D levels, a stratified sample of 29 controls was re-assayed at Heartland Assays and used to calibrate existing levels to a central assay using robust linear regression analyses. We standardized 25(OH) D levels for season using a periodic sine/cosine function. Conditional logistic regression analyses were performed in each study and were then pooled to generate pooled odds ratios by study-specific quantiles, consortium wide-quantiles, absolute cut points based on IOM guidance. Our preliminary analyses included 10,353 cases of incident invasive breast cancer (5305 estrogen receptor (ER) positive cases and 1311 (ER) negative cases and 12,313 matched controls. Median calibrated 25(OH)D levels in controls varied from 33 to 70 nmol/L across the cohorts. The consortium-wide median 25(OH)D among controls was 22% higher in summer as compared to winter months. Across all studies, median age at blood draw was 41 to 70 years; and median elapsed time from blood draw to diagnosis ranged from 2 to 13 years. The pooled odds ratio of breast cancer, comparing the highest to lowest study-specific 25(OH)D quintile, was 0.99 (95% confidence interval 0.90-1.08) after adjusting for body mass index, physical activity, menopausal status, menopausal hormone therapy use, parity/age at first birth, and family history of breast cancer. Results were not significantly different in analyses stratified by age of diagnosis ( In conclusion, preliminary results from the largest pooled analysis of prospective studies to date show no association between 25(OH)D levels and breast cancer risk and therefore suggest that increasing Vitamin D levels may not be an effective risk reduction strategy for breast cancer. Citation Format: Kala Visvanathan, Alison Mondul, Anne Zeleniuch-Jacquotte, Toqir K Mukhtar, Stephanie A Smith-Warner, Regina G Ziegler, On Behalf of Investigators in the Vitamin D Pooling Project of Breast and Colorectal Cancer. Circulating vitamin D concentrations and breast cancer risk: A pooled analysis of 17 cohorts [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-01.

BACKGROUND: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS: Compared with the lower range of sufficiency for bone health (50–

Background: Two indexes exist to describe dietary inflammatory potential: an empirical dietary inflammatory pattern (EDIP) composed of food groups as reported on a food-frequency questionnaire (FFQ) and a literature-derived dietary inflammatory index (DII) composed mainly of nutrients.Objective: We compared the ability of the 2 indexes to predict concentrations of inflammatory markers and hypothesized that the EDIP would be more predictive because it was derived on the basis of circulating inflammatory markers.Methods: Both EDIP and DII scores were calculated from FFQ data reported by 5826 women in the Nurses' Health Study II and 5227 men in the Health Professionals Follow-Up Study. We used multivariable-adjusted linear regression analyses to calculate relative differences in concentrations of 4 plasma inflammatory markers-C-reactive protein (CRP; milligrams per liter), interleukin 6 (IL-6; picograms per milliliter), tumor necrosis factor α receptor 2 (TNFαR2; picograms per milliliter), and adiponectin (nanograms per milliliter)-in quintiles of the dietary indexes.Results: Spearman correlations between the EDIP and DII scores were modest (r = 0.29 and 0.21 for women and men, respectively; all P < 0.0001). Higher scores on both dietary indexes were associated with higher concentrations of inflammatory markers, although they were associated with lower adiponectin concentrations and there was no association between the DII and adiponectin in men. For example, percentage differences in concentrations of biomarkers in quintile 5 generally were higher (lower for adiponectin) than in quintile 1 (for the EDIP and DII, respectively-women: CRP, +60% and +49%; IL-6, +23% and +21%; TNFαR2, +7% and +4%; adiponectin, -21% and -14%; men: CRP, +38% and +29%; IL-6, +14% and +24%; TNFαR2, +9% and +5%; adiponectin, -16% and -4%.)Conclusion: Despite design differences, the EDIP and DII both assess dietary inflammatory potential in men and women, with the EDIP showing a greater ability to predict concentrations of plasma inflammatory markers.

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: (1) the development of new statistical methods to address etiologic heterogeneity; (2) the enhancement of causal inference; (3) the identification of previously unknown exposure-subtype disease associations; and (4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields.

While early-life body leanness is associated with increased breast cancer risk, early-life physical activity may protect against breast cancer. We examined whether the excess risk among lean girls is modified by their levels of prior, concurrent, or future physical activity. We conducted an analysis among 74,723 women in the Nurses' Health Study II (follow-up 1997-2011). Participants recalled their body size at ages 5, 10 and 20 years in 1989 using a 9-level pictogram (Level 1 most lean). In 1997, they reported adolescent levels of physical activity (ages 12-13 and 14-17 years). Cox proportional hazards models estimated the overall association of body size with breast cancer risk and assessed interactions of adolescent physical activity with body size at three different age periods (5-10, 10-20 and 20 years), adjusting for early-life and adult risk factors for breast cancer. Regardless of levels of adolescent physical activity, early-life body leanness (level 1-2 vs. 4.5+) was significantly associated with higher breast cancer risk. The association was slightly attenuated among those who were active (60+ MET-hr/wk) during adolescence compared to those who were inactive (

The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race, and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p-trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP.

Background: Despite accumulating evidence for the preventive effect of vitamin D on colorectal carcinogenesis, its precise mechanisms remain unclear. We hypothesized that vitamin D was associated with a lower risk of colorectal cancer with high-level vitamin D receptor (VDR) expression, but not with risk of tumor with low-level VDR expression. Methods: Among 140,418 participants followed from 1986 through 2008 in the Nurses' Health Study and the Health Professionals' Follow-up Study, we identified 1,059 incident colorectal cancer cases with tumor molecular data. The predicted 25-hydroxyvitamin D [25(OH)D] score was developed using the known determinants of plasma 25(OH)D. We estimated the HR for cancer subtypes using the duplication method Cox proportional hazards model. Results: A higher predicted 25(OH)D score was associated with a lower risk of colorectal cancer irrespective of VDR expression level (Pheterogeneity for subtypes = 0.75). Multivariate HRs (95% confidence intervals) comparing the highest with the lowest quintile of predicted 25(OH)D scores were 0.48 (0.30–0.78) for VDR-negative tumor and 0.56 (0.42–0.75) for VDR-positive tumor. Similarly, the significant inverse associations of the predicted 25(OH)D score with colorectal cancer risk did not significantly differ by KRAS, BRAF, or PIK3CA status (Pheterogeneity for subtypes ≥ 0.22). Conclusions: A higher predicted vitamin D score was significantly associated with a lower colorectal cancer risk, regardless of VDR status and other molecular features examined. Impact: The preventive effect of vitamin D on colorectal carcinogenesis may not totally depend on tumor factors. Host factors (such as local and systemic immunity) may need to be considered. Cancer Epidemiol Biomarkers Prev; 23(8); 1628–37. ©2014 AACR.

Background: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. Objective: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses&rsquo, Health Study II among premenopausal women. Methods: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. Results: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): &minus, 18.6%, &minus, 3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (&minus, 11.3% with 95% CI: &minus, 18.3%, &minus, 3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (&minus, 18.0% with 95% CI: &minus, 27.9%, &minus, 6.7%, p-trend = 0.003). Conclusion: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS.

Background Epidemiological studies investigating the associations of coffee and tea intake with lung cancer risk have yielded inconsistent results. These previous studies included mostly lung cancer patients diagnosed among smokers. Because coffee and tea consumption are closely related to smoking behavior, these previous studies could suffer from biases due to residual confounding of smoking. To better characterize the relationship, a large study with a large number of lung cancer cases diagnosed among never smokers and detailed information on tea and coffee consumption, is needed. Using data from a large-scale pooled analysis that consists of over 1.2 million participants in the U.S. and Asia, we carried out a comprehensive evaluation on the association of coffee and tea intake with lung cancer risk. Methods Individual-level data from seven prospective cohort studies conducted in the U.S., and ten studies conducted in Asia, were included. Demographic, lifestyle, coffee and tea intake data were collected at the baseline survey for each study. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The first 2 years of follow-up time was excluded to minimize potential influence of reverse causality on study results. Subgroup analyses by smoking status, sex, race, histologic subtype and coffee type (caffeinated or decaffeinated) were also conducted to assess potential effect modification, as well as heterogeneity of the association. Results After a median follow-up of 8.6 years, 20,519 incident lung cancer cases were identified. Both coffee and tea consumption were associated with an increased risk of lung cancer. Comparing non-coffee and non-tea consumption, HRs for lung cancer associated with exclusive coffee drinkers (≥2 cups/day) among current, former and never smokers were 1.30 (95% CI, 1.15-1.47), 1.49 (1.27-1.74) and 1.41 (95% CI, 1.21-1.63), respectively. Similar positive associations were observed for caffeinated and decaffeinated coffee. The HRs associated with exclusive tea drinkers (>2 cups/day) were 1.16 (95% CI, 1.02-1.32), 1.10 (0.92, 1.32) and 1.37 (95% CI, 1.17-1.60) for current, former and never smokers, respectively. These associations did not differ significantly by sex, race or histologic subtypes. Conclusion A high consumption of coffee or tea was both associated with an increased risk of lung cancer regardless of race or smoking status. Our study included a large number of never-smoker lung cancer patients, which minimized potential confounding effects due to smoking. The positive association observed for both caffeinated and decaffeinated coffee suggests that compounds other than caffeine may play a role in the etiology of lung cancer. Citation Format: Jingjing Zhu, Wei Zheng, Rashimi Sinha, Stephanie A. Smith-Warner, Yong-Bing Xiang, Yikyung Park, Shoichiro Tsugane, Emily White, Woon-Puay Koh, Sue K. Park, Norie Sawada, Seiki Kanemura, Yumi Sugawara, Ichiro Tsuji, Kim Robien, Yasutake Tomata, Keun-Young Yoo, Jeongseon Kim, Jian-Min Yuan, Yu-Tang Gao, Yumie Takata, Eiko Saito, William Blot, Xiao-Ou Shu. Associations of coffee and tea consumption with lung cancer risk: A pooled analysis of 17 cohort studies involving over 1.2 million participants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 632.

Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with an improvement in survival among colorectal cancer (CRC) patients, but the relationships between plasma vitamin D binding protein (VDBP), bioavailable or free 25(OH)D, and CRC survival remain unknown. In two prospective cohort studies, the Health Professionals Follow-Up Study and the Nurses’ Health Study, we examined the association between prediagnostic plasma levels of VDBP, bioavailable 25(OH)D, and free 25(OH)D and survival among 604 participants diagnosed with CRC between 1991 and 2011. Plasma 25(OH)D and VDBP were directly measured, while bioavailable and free 25(OH)D were calculated using a validated formula based on total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall and CRC-specific mortality, adjusted for other prognostic markers and potential confounders. During the follow-up, there were 279 deaths, 177 of which were due to CRC (63%). Higher VDBP levels were associated with a significant improvement in overall and CRC-specific survival (Ptrend=0.005 and 0.02, respectively). Compared to patients in the lowest quartile, those in the highest quartile of VDBP had a multivariable-adjusted HR of 0.61 (95% confidence interval [CI], 0.42-0.89) for overall mortality and 0.56 (95% CI, 0.35-0.92) for CRC-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, no association with overall or CRC-specific mortality was observed for bioavailable or free 25(OH)D levels. In conclusion, higher prediagnostic plasma VDBP levels were associated with improved survival among CRC patients. The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action. Citation Format: Chen Yuan, Mingyang Song, Brian M. Wolpin, Jeffrey A. Meyerhardt, Shuji Ogino, Bruce W. Hollis, Andrew T. Chan, Charles S. Fuchs, Kana Wu, Molin Wang, Stephanie A. Smith-Warner, Edward L. Giovannucci, Kimmie Ng. Prediagnostic circulating concentrations of vitamin D binding protein and survival among colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3297.

Background: Tea and coffee have anti-inflammatory, anti-oxidant and neuroprotective effects mediated by a variety of compounds, including polyphenols. Observational studies suggest that tea and coffee intake may reduce risk of certain cancers, although the data on glioma risk are limited and inconclusive. Methods: We evaluated the association between tea, coffee, and caffeine intake and risk of glioma in the female Nurses’ Health Study (NHS, n=92,389, followed 33 years) and Nurses’ Health Study II (NHSII, n=95,242, followed 23 years) and the male Health Professionals Follow-up Study (HPFS, n=49,885, followed 29 years). Cumulatively updated tea and coffee intake were derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Age-adjusted hazard ratios of glioma by category of beverage intake were estimated using Cox proportional hazards models. Associations across the combined cohorts were calculated using fixed effect meta-analysis. Results: We documented 554 incident cases of glioma, including 256 in NHS, 87 in NHSII, and 211 in HPFS (159, 52, 151 glioblastomas, respectively). Compared to 2 cups/day, p-trend=0.03), and was inversely, but not significantly, associated in men (HR=0.70, 95%CI 0.30-1.61 for >2 cups/day, p-trend=0.30). In women and men combined, the corresponding HR was 0.66 (95% CI 0.44-0.99) for >2 cups/day (p-trend=0.02). We observed no significant associations between caffeinated, decaffeinated, or total coffee intake and glioma risk in men or women. We found no material differences in the results when baseline values were used, when responses were lagged by eight years, or when cases were limited to glioblastoma only. Conclusion: In three large, prospective cohort studies of men and women, tea intake was inversely associated with glioma risk, particularly in women. No significant associations were observed for coffee intake of any type and glioma risk. These results merit further exploration in other prospective studies. Note: This abstract was not presented at the meeting. Citation Format: David J. Cote, Alaina M. Bever, Kathryn M. Wilson, Timothy R. Smith, Stephanie A. Smith-Warner, Meir Stampfer. A prospective study of tea and coffee intake and risk of glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 637.

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.

Carotenoids have been hypothesized to prevent carcinogenesis through their antioxidant and pro-vitamin A properties. We examined associations between intakes of specific carotenoids and risk of colorectal adenomas.Among 29,363 men who reported having a lower bowel endoscopy between 1986 and 2006, 3,997 cases of colorectal adenoma were identified in the Health Professionals Follow-up Study. Participants completed food frequency questionnaires every 4 years; dietary information was cumulatively updated. The associations between carotenoid intakes and risk of colorectal adenomas overall and by anatomic site, stage, smoking status and alcohol consumption were investigated using multivariate logistic regression models.Total β-carotene and dietary β-carotene, lycopene and lutein/zeaxanthin intakes and the total carotenoid score were inversely associated with colorectal adenoma risk. The odds ratios (95 % confidence intervals) comparing the highest versus lowest quintile of intake were 0.78 (0.69-0.88) for total β-carotene, 0.72 (0.64-0.81) for dietary β-carotene, 0.83 (0.74-0.93) for lycopene, 0.86 (0.76-0.96) for lutein/zeaxanthin, and 0.87 (0.77-0.97) for the total carotenoid score. Associations for α-carotene and β-cryptoxanthin intakes were null. We did not find significant differences in the associations between intakes of each carotenoid and risk of colorectal adenoma by anatomic site or stage (all p values, test for common effects0.10). The inverse associations we observed for total β-carotene and dietary β-carotene, lycopene, and lutein/zeaxanthin intakes and the total carotenoid score with adenoma risk also did not vary by smoking status and alcohol consumption.This study found that a diet high in carotenoids was associated with a reduced risk of colorectal adenomas.

Although expression of estrogen receptor (ER), progesterone receptor (PR), and cell proliferation marker Ki67 serve as predictive and prognostic factors in breast cancers, little is known about their roles in normal breast tissue. Here in a nested case–control study within the Nurses’ Health Studies (90 cases, 297 controls), we evaluated their expression levels in normal breast epithelium in relation to subsequent breast cancer risk among women with benign breast disease. Tissue microarrays were constructed using cores obtained from benign biopsies containing normal terminal duct lobular units and immunohistochemical stained for these markers. We found PR and Ki67 expression was non-significantly but positively associated with subsequent breast cancer risk, whereas ER expression was non-significantly inversely associated. After stratifying by lesion subtype, Ki67 was significantly associated with higher risk among women with proliferative lesions with atypical hyperplasia. However, given the small sample size, further studies are required to confirm these results.

Healthy diets may lower oxidative stress and risk of chronic diseases. However, no previous studies examined associations between diet and fluorescent oxidation products (FlOP), a global marker of oxidative stress. We evaluated associations between healthy eating patterns (Alternative Healthy Eating Index (AHEI), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (aMED)) and FlOP, measured at three excitation/emission wavelengths (FlOP_360, FlOP_320, FlOP_400) from 2021 blood samples collected from 1688 women within the Nurses’ Health Study. AHEI, DASH, and aMED scores were significantly positively associated with FlOP_360 and FlOP_320 concentrations (p-trend ≤ 0.04), but not associated with FlOP_400. Among specific food groups that contribute to these diet scores, significantly positive associations were observed with legumes and vegetables for FlOP_360, vegetables and fruits for FlOP_320, and legumes and alcohol for FlOP_400. Inverse associations were observed with nuts, sweets or desserts, and olive oil for FlOP_360, nuts for FlOP_320 and sweets or desserts for FlOP_400 (all p-trend ≤ 0.05). However, FlOP variation due to diet was small compared to overall FlOP variation. In conclusion, AHEI, DASH, and aMED scores were unexpectedly positively, but weakly, associated with FlOP_360 and FlOP_320. However, these findings should be interpreted cautiously as the determinants of FlOP concentrations are not fully understood.

The relationship between calcium intake and colorectal cancer (CRC) risk remains inconclusive. We conducted this study to evaluate whether the association between calcium intake and CRC risk differs by anatomic subsite and determine the dose-response relationship for this association, as well as assess when in carcinogenesis calcium may play a role. We assessed calcium intake every 4 years and followed 88,509 women (1980-2012) in the Nurses' Health Study and 47,740 men (1986-2012) in the Health Professionals Follow-Up Study. We documented 3,078 incident CRC cases. Total calcium intake (≥1,400 vs.

Adherence to the 2007 WCRF/AICR cancer prevention recommendations has been associated with lower cancer risk but the underlying biological mechanisms have not been elucidated. We utilized dietary and lifestyle data from 11,342 women in the Nurses' Health Study and 8,136 men in the Health Professionals Follow-up Study, to investigate associations between adherence scores and markers of inflammation, hormonal and insulin response. Two scores ranging from 0 to 3 were constructed to assess adherence to the energy balance-related recommendations (weight management, physical activity, energy density); and the plant, animal foods and alcohol intake recommendations; with higher scores indicating greater adherence. The following biomarkers were assessed in plasma samples donated by chronic disease-free women (1990) and men (1994): C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α receptor 2 (TNFαR2) and adiponectin for inflammation; estrone and estradiol for hormonal response in women, C-peptide for hyperinsulinemia; and triglycerides/high density lipoprotein-cholesterol (TG/HDL) ratio for insulin resistance. In multivariable-adjusted linear regression analyses, we estimated relative concentrations of biomarkers across adherence categories. There was a significant trend of lower (higher for adiponectin) biomarker concentrations with higher adherence to the energy balance recommendations (all p trend0.0001). Comparing the highest (3) to the lowest recommendation category (0-1), the percent difference in relative concentrations of biomarkers was CRP, -69%; IL6, -41%; TNFαR2, -13%; adiponectin, +36%; C-peptide, -43%; TG/HDL, -43%; estrone, -31%; and estradiol, -43%; in women; and CRP, -59%; IL6, -42%; TNFαR2, -10%; adiponectin, +22%; C-peptide, -44%; and TG/HDL, -40%; in men. In contrast, associations between adherence to the plant, animal foods and alcohol intake recommendations and biomarker concentrations were weaker, and mostly nonsignificant. The healthier biomarker profile associated with greater adherence to the WCRF/AICR cancer prevention recommendations is driven mainly by adherence to the energy balance-related recommendations.

Background Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. Methods During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. Results Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. Conclusions Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.

Purpose The associations between use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen and breast cancer incidence in postmenopausal women are uncertain. We examined these associations with breast cancer, both overall and by molecular subtype. Patients and Methods We observed 84,602 postmenopausal women, free of cancer in 1980, until June 2008 and prospectively collected data on analgesic use, reproductive history, and other lifestyle factors using biennial questionnaires. Proportional hazards models were used to estimate multivariable relative risks (RRs) and 95% CIs. Results We documented 4,734 cases of incident invasive breast cancer. Compared with nonuse of aspirin, multivariable RRs of regular aspirin use (≥ two tablets per week) for more than 20 years were 0.91 for overall breast cancer (95% CI, 0.81 to 1.01; Ptrend = 0.16), 0.90 for estrogen receptor (ER) –positive progesterone receptor (PR) –positive breast cancer (95% CI, 0.77 to 1.06; Ptrend = 0.17), and 0.91 for ER-negative PR-negative breast cancer (95% CI, 0.68 to 1.22; Ptrend = 0.97). Results did not vary appreciably by past or current use, days per week of use, or dosage of use. Use of other NSAIDs and acetaminophen was largely not significantly associated with breast cancer risk. Additionally, use of higher doses of each analgesic (≥ six tablets per week) for more than 10 years was generally not significantly associated with risk of breast cancer, either overall or by subtype. Furthermore, largely no substantial associations were noted for breast cancer molecular subtypes, including luminal A, luminal B, triple negative, basal-like, human epidermal growth factor receptor 2 positive, cyclooxygenase-2 (COX-2) negative, and COX-2 positive. Conclusion Our study suggests that use of aspirin, other NSAIDs, and acetaminophen is not importantly associated with risk of postmenopausal breast cancer, either overall or by specific subtype.

BACKGROUND: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD: We tested magnesium–colorectal cancer hypothesis in the Nurses’ Health Study, in which 85924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). RESULTS: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (Ptrendo0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (Ptrend ¼0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (Ptrend ¼0.002) but not in multivariate-adjusted model (Ptrend ¼0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. CONCLUSION: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women.

Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER−) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER− and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER−, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.

Global burdens of cardiovascular disease (CVD), diabetes and cancer are on the rise. Little quantitative data are available on the global impact of diet on these conditions. The objective of this study was to develop systematic and comparable methods to quantitatively assess the impact of suboptimal dietary habits on CVD, diabetes and cancer burdens globally and in 21 world regions. Using a comparative risk assessment framework, we developed methods to establish for selected dietary risk factors the effect sizes of probable or convincing causal diet–disease relationships, the alternative minimum-risk exposure distributions and the exposure distributions. These inputs, together with disease-specific mortality rates, allow computation of the numbers of events attributable to each dietary factor. Using World Health Organization and similar evidence criteria for convincing/probable causal effects, we identified 14 potential diet–disease relationships. Effect sizes and ranges of uncertainty will be derived from systematic reviews and meta-analyses of trials or high-quality observational studies. Alternative minimum-risk distributions were identified based on amounts corresponding to the lowest disease rates in populations. Optimal and alternative definitions for each exposure were established based on the data used to quantify harmful or protective effects. We developed methods for identifying and obtaining data from nationally representative surveys. A ranking scale was developed to assess survey quality and validity of dietary assessment methods. Multi-level hierarchical models will be developed to impute missing data. These new methods will allow, for the first time, assessment of the global impact of specific dietary factors on chronic disease mortality. Such global assessment is not only possible but is also imperative for priority setting and policy making.

Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m(2), pancreatic cancer risk was 47% higher (95% CI:23-75%) among obese (BMI >= 30 kg/m(2)) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI >= 25 kg/m(2) to a BMI between 21 and 22.9 kg/m(2)). Compared to individuals who were not overweight in early adulthood (BMI = 10 kg/m(2) between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.

Attention to cancer-relevant communication (e.g., fruit/vegetable intake recommendations) through various media has been shown to be a pivotal step in reduction of the cancer burden, thus underscoring the importance of examining associations between exposure to health media and knowledge of and adherence to fruit/vegetable intake recommendations. The purpose of the present study was to assess factors associated with fruit/vegetable intake knowledge and behavior. The authors analyzed data collected from the 2003 Health Information National Trends Survey to evaluate the effect of fruit/vegetable intake knowledge on behavior, and the relationship of this effect with biobehavioral, sociodemographic, and communication characteristics. Participants who were knowledgeable of fruit/vegetable intake recommendations and consumed at least 5 fruit/vegetable servings per day were classified as informed compliers. Associations were observed for being an informed complier and paying "a lot" of attention to health media on the radio, in the newspaper, and in magazines and "a little" or "some" attention to health media in magazines or on the Internet. The recent explosion of available cancer-related information through various media underscores the importance of examining associations between exposure to health media and knowledge of and adherence to fruit/vegetable intake recommendations.

High dietary fiber intake has been associated with a lower risk of many cancers but evidence from epidemiological studies on dietary fiber intake and risk of advanced prostate cancer and prostate cancer mortality are limited. We examined associations between dietary fiber intakes overall and from grains, fruits, and vegetables and risk of prostate cancer in 15 cohorts in the Pooling Project of Prospective Studies of Diet and Cancer. Among 842,149 men, during maximum follow-up ranging from 9.2-21.9 years across studies, 52,683 incident prostate cancer cases were identified. Prostate cancer outcomes examined were: 1) all cases; 2) advanced cases, which included men with advanced stage prostate cancer at diagnosis (T4, N1, and/or M1) and men who died of prostate cancer during follow-up (n=4,924); 3) advanced (restricted) cases, which included only men with advanced stage prostate cancer at diagnosis (n=3,110) (men diagnosed with localized prostate cancer who died of prostate cancer were excluded) and 4) prostate cancer mortality, death due to prostate cancer (n=3,199). We adjusted dietary fiber intake for energy intake using the residual method. Cox proportional hazards models were used to calculate study-specific multivariable relative risks (MVRR); the study-specific results were pooled using random effects models. Models were adjusted for age, race/ethnicity, education, marital status, body mass index, height, smoking status, family history of prostate cancer, physical activity, history of diabetes, multivitamin use, and energy and alcohol intake. Median dietary fiber intake varied from 6-28 g/d across studies. For total dietary fiber intake, dietary fiber intake from fruits, and dietary fiber intake from vegetables, no statistically significant associations were observed for any outcome; the pooled MVRRs comparing the highest with the lowest quintile ranged from 0.95-1.02. The pooled MVRR comparing the highest with the lowest study-specific quintile of dietary fiber intake from grains was 0.84 (95% confidence interval [CI] 0.76-0.93) for advanced stage and 0.85 (0.74-0.97) for advanced (restricted) stage prostate cancer. The pooled MVRR for the same comparison was 0.78 (95% CI 0.69-0.89) for prostate cancer mortality. Similar results were observed when dietary fiber intake was categorized using common absolute intake cutpoints across studies (e.g., the pooled MVRR for prostate cancer mortality was 0.86, 95% CI 0.75-0.98 comparing ≥8 with Citation Format: Elkhansa Sidahmed, Stephen J. Freedland, Molin Wang, Kana Wu, Jeanine M. Genkinger, Stephanie A. Smith-Warner. A pooled analysis of dietary fiber intake and risk of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5255.

Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the second-leading cause of cancer-related death worldwide. In the U.S., the incidence rate of HCC has tripled since 1975. Although preliminary evidence suggesting a biological impact of diet on multiple inflammatory pathways implicated in hepatocarcinogenesis, the most comprehensive review by the WCRF/AICR concluded that the relationship between diet and HCC remains largely unknown. HCC is an inflammation-related cancer but few studies have investigated diet quality based on its inflammatory potential in relation to HCC risk. The empirical dietary inflammatory pattern scores (EDIP) score were calculated from validated food frequency questionnaires. It characterized dietary inflammatory potential based on circulating levels of inflammatory bio-markers. We prospectively followed 49,674 men in the Health Professionals Follow-up Study (1986-2012), and 74,139 women in the Nurses' Health Study (1984-2012). Cox regression analyses were used to calculate hazards ratios (HR) for HCC risk adjusting for body mass index, smoking, history of diabetes, race, physical activity, and regular aspirin use. We documented a total of 89 incident HCC cases (44 in women and 45 in men) over 28 years, encompassing 1,522,972 person-years of follow-up. Compared to the lowest tertile, the highest tertile of the EDIP score was associated with a multivariable HR for HCC of 2.86 (95%CI, 1.20-6.81) among women (P-trend=0.01) and of 0.68 (95%CI, 0.31-1.50) among men (P-trend=0.35). Future study is warranted to confirm this finding and elucidate the potential biological basis. Key words: inflammation, dietary patterns, HCC A. T. C. and X. Z contributed equally to this work. Citation Format: Yanan Ma, Tracey G. Simon, Fred K Tabung, Lindsay Y. King, Dawn Q. Chong, Long Nguyen, Trang VoPham, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kathleen E. Corey, Hamed Khalili, Stephanie Smith-Warner, Raymond T. Chung, Edward L. Giovannucci, Andrew T. Chan, Xuehong Zhang. A prospective study of inflammatory diet potential and risk of hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5256.

Background: The relationship between calcium intake and colorectal cancer risk remains inconclusive. Calcium may enhance T-cell proliferation and differentiation, and contribute to T cell-mediated antitumor immunity. Investigating the calcium and colorectal cancer association according to tumor immunity status may provide additional insights into the role of calcium in colorectal carcinogenesis. Methods: We thus investigated whether the association between calcium intake and colorectal cancer risk differs by tumor subtypes according to the density of tumor-infiltrating CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells. A total of 88,509 U.S. female registered nurses from the Nurses' Health Study and 47,740 U.S. male professionals from the Health Professionals Follow-up Study were included in the analysis. Total calcium intake from food and supplemental sources was collected at baseline and every 4 years using validated food frequency questionnaires. The densities of tumor-infiltrating T-cell subsets (CD3+, CD8+, CD45RO+, or FOXP3+ cell) was assessed using immunohistochemical and computer-assisted image analysis. Results: We identified 736 incident colorectal adenocarcinoma cases during follow-up with available data on T-cell infiltration in tumor tissue. Compared to calcium intake of 0.01, with the adjusted α of 0.01 by Bonferroni correction). Additionally, these differential associations appeared to persist regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status (MSI). Conclusions: Higher calcium intake appears to be primarily associated with lower risk of colorectal cancer containing low densities of T cells, but not with cancers containing high densities of T cells. This finding supports a possible role of calcium in cancer immunoprevention via modulation of T-cell function. Citation Format: Wanshui Yang, Li Liu, NaNa Keum, Zhi Rong Qian, Jonathan A. Nowak, Tsuyoshi Hamada, Mingyang Song, Yin Cao, Katsuhiko Nosho, Stephanie A. Smith-Warner, Shui Zhang, Yohei Masugi, Kimmie Ng, Keisuke Kosumi, Yanan Ma, Wendy S. Garrett, Molin Wang, Hongmei Nan, Marios Giannakis, Jeffrey A. Meyerhardt, Andrew T. Chan, Charles S. Fuchs, Reiko Nishihara, Kana Wu, Edward L. Giovannucci, Shuji Ogino, Xuehong Zhang. Calcium intake and risk of colorectal cancer according to tumor-infiltrating T cells: Results from two large U.S. prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 693.

To examine the association between total antioxidant capacity (TAC) intake and colorectal cancer incidence.TAC intake was assessed in 1986 and every 4 years thereafter in the Health Professionals Follow-up Study, a prospective cohort study of 47,339 men. Between 1986 and 2004, 952 colorectal cancer cases were diagnosed. Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).Comparing the highest versus lowest quintile, TAC intake from foods only (dietary TAC) was not associated with colorectal (multivariate-RR: 0.98; 95% CI: 0.78, 1.23) or colon (multivariate-RR: 1.20; 95% CI: 0.90, 1.61) cancer risk, but was inversely associated with rectal cancer risk (multivariate-RR: 0.58; 95% CI: 0.35, 0.96). For the same comparison, TAC intake from foods and supplements (total TAC) was not associated with colorectal (multivariate-RR: 0.91; 95% CI: 0.73, 1.14), colon (multivariate-RR: 1.01; 95% CI: 0.77, 1.33), or rectal (multivariate-RR: 0.85; 95% CI: 0.52, 1.38) cancer risk.Dietary and total TAC intakes were not associated with colorectal and colon cancer risk. Dietary, but not total, TAC intake was inversely associated with rectal cancer risk, suggesting antioxidants per se may not be associated with rectal cancer risk.

Few studies have examined the association between coffee intake and survival after diagnosis of colorectal cancer (CRC). We performed a prospective study to investigate the association between coffee intake after a diagnosis of CRC and mortality.We collected data from the Nurses' Health Study (1984-2012) and Health Professionals Follow-up Study (1986-2012), following 1599 patients diagnosed with stage 1, 2, or 3 CRC. CRC was reported on questionnaires and ascertained by review of medical records and pathology reports; intake of food and beverages was determined from responses to semi-quantitative food frequency questionnaires. Participants were asked how often during the previous year that they consumed coffee, with 1 cup as the standard portion size. The first questionnaire response collected at least 6 months but not more than 4 years after diagnosis was used for assessment of post-diagnostic intake (median time from diagnosis to the dietary assessment, 2.2 years). The last semi-quantitative food frequency questionnaire prior to diagnosis was used to assess pre-diagnostic dietary intake.During a median of 7.8 years of follow-up, we documented 803 deaths, of which 188 were because of CRC. In the multivariable adjusted models, compared with nondrinkers, patients who consumed at least 4 cups of coffee per day had a 52% lower risk of CRC-specific death (hazard ratio [HR] 0.48; 95% CI, 0.28-0.83; P for trend=.003) and 30% reduced risk of all-cause death (HR, 0.70; 95% CI, 0.54-0.91; P for trend.001). High intake of caffeinated and decaffeinated coffee (2 or more cups/day) was associated with lower risk of CRC-specific mortality and all-cause mortality. When coffee intake before vs after CRC diagnosis were examined, compared with patients consistently consuming low amounts (less than 2 cups/day), those who maintained a high intake (2 or more cups/day) had a significantly lower risk of CRC-specific death (multivariable HR, 0.63; 95% CI, 0.44-0.89) and death from any cause (multivariable HR, 0.71; 95% CI, 0.60-0.85).In an analysis data from the Nurses' Health Study and Health Professionals Follow-up Study, we associated intake of caffeinated and decaffeinated coffee after diagnosis of CRC with lower risk of CRC-specific death and overall death. Studies are needed to determine the mechanisms by which coffee might reduce CRC progression.

Importance Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. Objective To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers. Design, Settings, and Participants Cohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses’ Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017. Exposures EDIP scores calculated from food frequency questionnaires administered every 4 years. Main Outcomes and Measures Incident colorectal cancer. Results We documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR], 1.44; 95% CI, 1.19-1.74; P P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33; 95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight, with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI, 1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99-1.74; P = .01 for trend). Conclusions and Relevance Findings suggest that inflammation is a potential mechanism linking dietary patterns and colorectal cancer development. Interventions to reduce the adverse role of proinflammatory diets may be more effective among overweight/obese men and lean women or men and women who do not consume alcohol.

Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RR) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with

Limited research has examined the association of diet with immigrant status, adjusting for multiple socio-demographic and contextual influences. Among 662 WIC-eligible postpartum women, those who were foreign-born and had lived in the United States for 4 or fewer years consumed 2.5 more fruit and vegetable servings daily than native-born women; this difference diminished with longer US residence. White women consumed 1 serving less than Latinas, and those speaking both English and Spanish at home consumed 1.4 servings more than English-only speakers after adjusting for other covariates.

Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; pvalue, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer. (c) 2007 Wiley-Liss, Inc. AD - Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable.

A recent meta-analysis found that sedentary behaviors are associated with an increased colorectal cancer (CRC) risk. Yet, the finding on TV viewing time, the most widely used surrogate of sedentary behaviors, was based on only two studies. Furthermore, light-intensity activities (e.g., standing and slow walking), non-sedentary by posture but close to sedentary behaviors by Metabolic Equivalent Task values, have not been investigated in relation to CRC risk. Thus, we prospectively analyzed the relationships based on 69,715 women from Nurses' Health Study (1992-2010) and 36,806 men from Health Professionals Follow-Up Study (1988 - 2010). Throughout follow-up, time spent on sedentary behaviors including sitting watching TV and on light-intensity activities were assessed repeatedly; incidence of CRC was ascertained. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models from each cohort. A total of 1,119 and 913 incident cases were documented from women and men, respectively. The multivariable HR comparing ≥ 21 versus7 hr/week of sitting watching TV was 1.21 (95% CI = 1.02 to 1.43, ptrend =.01) in women and 1.06 (95% CI = 0.84 to 1.34, ptrend =.93) in men. In women, those highly sedentary and physically less active had an approximately 41% elevated risk of CRC (95% CI = 1.03 to 1.92) compared with those less sedentary and physically more active. The other sedentary behaviors and light-intensity activities were not related to CRC risk in women or men. In conclusion, we found that prolonged sitting time watching TV was associated with an increased CRC risk in women but not in men.

Background: Interindividual differences in the bioavailability of potentially carcinogenic estrogen and estrogen metabolites (EMs) may play a role in the risk of breast cancer. Objective: We examined whether dietary intakes of fiber and fat influence premenopausal EM profiles through effects on estrogen synthesis, metabolism, or excretion. Methods: We conducted a cross-sectional analysisof598 premenopausal womenwho participated in a reproducibility study (n = 109) or served as controls in a nested case-control study of breast cancer (n = 489) within the Nurses Health Study II. Dietary intakes of fiber and fat were assessed via semiquantitative food frequency questionnaires in 1995 and 1999. Midluteal urine samples were collected between 1996 and 1999 and EMs were quantified with the use of HPLC-tandem mass spectrometry. Linear mixed models were used to estimate creatinine-adjusted geometric means for individual EMs and their pathway groups across categories of dietary intake while controlling for total energy intake and potential confounders. Results: Higher total dietary fiber intake (>25 g/d vs. #15 g/d) was associated with significantly higher concentrations of 4-methoxyestradiol (50% difference, P-difference = 0.01, P-trend = 0.004) and lower concentrations of 17-epiestriol (227% difference, P-difference = 0.03, P-trend = 0.03), but was not associated with any other EMs. The associations did not vary byfiber intake from different sources. Total fat intake (>35% energy vs. #25% energy) was suggestively positively associated with 17-epiestriol (22.6% difference, P-difference = 0.14, P-trend = 0.06); the association was significant for polyunsaturated fatty acid (37% difference, P-difference = 0.01, P-trend = 0.01) and trans fat (36.1% difference, P-difference = 0.01, P-trend = 0.01) intakes. Conclusion: Fiber and fat intakes were not strongly associated with patterns of estrogen metabolism in premenopausal women. Our data suggest estrogen metabolism is not a major mechanism through which dietary fiber and fat may affect breast or other hormone-related cancer risks. J Nutr 2015;145:2109‐16.

Background: Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer. However, few prospective studies have examined the intakes of fruits, vegetables, and antioxidant vitamins in relation to the risk of renal cell cancer. Methods: We prospectively examined the associations between the intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer in women and men. We followed 88,759 women in the Nurses' Health Study from 1980 to 2000, and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000. We assessed dietary intake every 2 to 4 years using a validated semiquantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random effects model. Results: A total of 248 (132 women and 116 men) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up. The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men (multivariate RR, 0.45; 95% CI, 0.25-0.81, for ≥6 servings of fruit and vegetable intake/d versus Conclusions: Fruit and vegetable consumption may reduce the risk of renal cell cancer in men. (Cancer Epidemiol Biomarkers Prev 2006;12(24):2445–52)

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 μg/day increase in α-carotene intake, 0.96 (0.93-1.03) for a 2,500 μg/day increase in β-carotene intake, 0.99 (0.97-1.02) for a 100 μg/day increase in β-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 μg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 μg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer. © 2006 Wiley-Liss, Inc.

With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.

Background: Dairy foods and their constituents (lactose and calcium) have been hypothesized to promote ovarian carcinogenesis. Although case-control studies have reported conflicting results for dairy foods and lactose, several cohort studies have shown positive associations between skim milk, lactose, and ovarian cancer. Methods: A pooled analysis of the primary data from 12 prospective cohort studies was conducted. The study population consisted of 553,217 women among whom 2,132 epithelial ovarian cases were identified. Study-specific relative risks and 95% confidence intervals were calculated by Cox proportional hazards models and then pooled by a random-effects model. Results: No statistically significant associations were observed between intakes of milk, cheese, yogurt, ice cream, and dietary and total calcium intake and risk of ovarian cancer. Higher lactose intakes comparing ≥30 versus Discussion: Overall, no associations were observed for intakes of specific dairy foods or calcium and ovarian cancer risk. A modest elevation in the risk of ovarian cancer was seen for lactose intake at the level that was equivalent to three or more servings of milk per day. Because a new dietary guideline recommends two to three servings of dairy products per day, the relation between dairy product consumption and ovarian cancer risk at these consumption levels deserves further examination. (Cancer Epidemiol Biomarkers Prev 2006;15(2):364–72)

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk. (c) 2005 Wiley-Liss, Inc.

KEYWORDS - CLASSIFICATION: adverse effects;analysis;Boston;cancer epidemiology;Cholesterol;Cohort Studies;dietary modulation of cancer & cancer biomarkers;Dietary Fats;epidemiology;etiology;Eggs;Female;Food Habits;Humans;North America;Ovarian Neoplasms;Public Health;Research;Risk. Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30

Context: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective: To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants: From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. Main Outcome Measure: Incident colorectal cancer. Results: During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR=0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR=0.94; 95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to

Intervention trials with supplemental β-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7–16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. β-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87–1.11; highest versus lowest quintile). The RRs for α-carotene, lutein/zeaxanthin, and lycopene were also close to unity. β-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67–0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in β-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

Body fatness is an established risk factor for postmenopausal breast cancer, but it is unknown if this risk associated with excess body weight is reversible. We conducted a pooled analysis of 11 prospective studies in the Pooling Project of Prospective Studies of Diet and Cancer. Each study had adult body weight data at three time points, as well as follow-up for subsequent risk of breast cancer after the third weight measure. Weight change was assessed using reported or measured weight at baseline and two follow-up time points, each generally four to six years apart (over a total of ~10 years). Stable weight for each interval was defined as weight within 2kg of the previous weight. The referent group was women with stable weight (within 2kg) at all three time points across the 10-year period. Among 340,055 women, 10,427 breast cancers were diagnosed during follow-up. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) controlling for baseline body mass index (BMI), baseline physical activity, and postmenopausal hormone (PMH) use at the start of breast cancer follow-up, were estimated using proportional hazards regression on an aggregated dataset from all studies. Women who lost weight and kept the weight off, were at a lower risk of breast cancer than women with stable weight over the 10 years: >2.-4.5kg lost between baseline and the first follow-up body weight measure (n=482 cases): HR=0.92, 95% CI: 0.83-1.03; >4.5-9kg lost (n=283 cases): HR=0.86, 95% CI: 0.76-0.98; >9kg lost (n=95 cases): HR =0.81, 95%CI: 0.65-1.00). Women who initially lost weight (>2kg), but then re-gained it had a similar risk of breast cancer to those with stable weight over the same time period. When results were stratified by baseline age and BMI, there was no association between sustained weight loss and breast cancer among women younger than 50 years, nor those with a normal BMI (18.5-25 kg/m2) before weight loss. Among women who were aged 50 or more years and overweight or obese before the weight loss period, we observed a 21% lower risk of breast cancer for sustained weight loss of ≥4.5kg compared to women with stable weight over the same time period (n=245 cases, HR=0.79, 95% CI: 0.68-0.93). This observed association was driven by women who were not taking PMH (n=156, HR=0.71, 95% CI: 0.58-0.86). In this large, pooled prospective analysis of weight loss and breast cancer risk we found that losing 4.5 kg—and keeping it off—may lower breast cancer risk, particularly for women older than 50 who are overweight or obese. The results may provide motivation for women with elevated BMI to lose weight and potentially reduce their risk of breast cancer. Citation Format: Lauren R. Teras, Alpa V. Patel, Molin Wang, Bette J. Caan, Yu Chen, Avonne E. Connor, A. Heather Eliassen, Susan M. Gapstur, Mia M. Gaudet, Jeanine M. Genkinger, Graham G. Giles, I-Min Lee, Roger Milne, Norie Sawada, Howard D. Sesso, Meir Stampfer, Rulla Tamimi, Cynthia A. Thomson, Shoichiro Tsugane, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Walter C. Willett, Stephanie A. Smith-Warner. Weight loss over 10 years of adulthood and subsequent risk of breast cancer: a pooled analysis of 11 cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2017-5311

While early-life body leanness is associated with increased breast cancer risk, early-life physical activity may protect against breast cancer. We examined whether the excess risk among lean girls is modified by their levels of prior, concurrent, or future physical activity. We conducted an analysis among 74,723 women in the Nurses' Health Study II (follow-up 1997-2011). Participants recalled their body size at ages 5, 10 and 20 years in 1989 using a 9-level pictogram (Level 1 most lean). In 1997, they reported adolescent levels of physical activity (ages 12-13 and 14-17 years). Cox proportional hazards models estimated the overall association of body size with breast cancer risk and assessed interactions of adolescent physical activity with body size at three different age periods (5-10, 10-20 and 20 years), adjusting for early-life and adult risk factors for breast cancer. Regardless of levels of adolescent physical activity, early-life body leanness (level 1-2 vs. 4.5+) was significantly associated with higher breast cancer risk. The association was slightly attenuated among those who were active (60+ MET-hr/wk) during adolescence compared to those who were inactive (30 MET-hr/wk) (body size at ages 5-10 years: hazard ratio = 1.37, 95% confidence interval = 1.04-1.81 vs. 1.66, 1.29-2.12), but the interaction was not significant (p = 0.72). The results were similar for body size at three different age periods. Being lean during early life is a risk factor for breast cancer among both inactive and active girls. Adolescent physical activity did not significantly modify the association, although some interaction cannot be excluded.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and icecream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with

The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR = 0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR = 0.82, 95% CI 0.54-1.26, and OR = 0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP.