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BackgroundAlthough most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear.MethodsWe examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified.ResultsAfter adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with

Background: A high body mass index (BMI, kg/m 2 ) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology., Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy., Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO., Conclusion: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55., Competing Interests: Declaration of Competing Interest none., (Published by Elsevier Ltd.)

Purpose: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer., Methods: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity., Results: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( P nonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; P het = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity., Conclusion: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Background: Healthy dietary patterns characterized by high intake of fruits and vegetables, grains/cereals, and lean meat/fish, and low intake of red/processed meats and refined carbohydrates, have been shown to be associated with reduced risk of colorectal cancer, but evidence regarding their association with colorectal cancer subsites is limited. Hence, this study was conducted to assess the association of a healthy dietary pattern, as reflected in the Healthy Eating Index (HEI) (a composite score based on consumption of various food groups), with risk of colorectal cancer, overall and by subsite., Methods: We conducted a case-cohort study in the Canadian Study of Diet, Lifestyle and Health (CSDLH). The study included all cases of incident colorectal cancer in the entire cohort, and an age-stratified subcohort of 3185 women and 2622 men. Cox regression models were used to estimate hazard ratios (HR) for the association between the HEI and the risk of colorectal cancer, overall and by subsite. We also assessed the association by sex and by selected metabolic factors., Results: For both sexes combined, the highest quintile of the HEI score was inversely associated with risk of colorectal cancer, colon cancer and proximal colon cancer (HR: 0.65; 95% CI: 0. 49-0.85, HR: 0.60, 95% CI: 0.44-0.83 and HR: 0.54, 95% CI: 0.35-0.85, respectively). However, these associations were mostly observed among men (HR: 0.56; 95% CI: 0.38-0.81, HR: 0.44, 95% CI: 0.28-0.69 and HR: 0.26; 95% CI: 0.12-0.56, for colorectal cancer, colon cancer and proximal colon cancer, respectively; p-interactions=0.029, 0.032 and 0.063, respectively). An inverse association was also observed between the HEI and risk of colorectal cancer among normal weight participants, overweight/obese participants, non-smokers, non-alcohol drinkers and participants who were physically inactive., Conclusion: A healthy dietary pattern may reduce risk of colorectal cancer, particularly among men., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity., Methods: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age., Results: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia., Interpretation: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity., Competing Interests: Competing interests: Maureen Anderson reports receiving a Saskatchewan Health Research Foundation Establishment Grant, in support of the present manuscript. Lesley Behl reports receving funding from the CITF via a research grant paid to the University of Saskatchewan, in support of the present manuscript. Patrick Brown reports receiving grant support from the CITF. Carmen Charlton reports receiving grant funding from Merck and support for attending meetings or travel from AMMI Canada. Karen Colwill reports receiving an honorarium for a presentation to the Ontario Society of Clinical Chemists. Dr. Colwill is also the vice president of communications for the Canadian National Proteomics Network. Tim Evans reports receiving support for the present manuscript from the CITF, and holds the role of its executive director. Anne-Claude Gingras reports receiving support for automated equipment for ELISA, housed at the Lunenfeld-Tanenbaum Research Institute (a facility supported by Canada Foundation for Innovation funding, the Ontario Government, Genome Canada and Ontario Genomics); support from the Canadian Institutes of Health Research (CIHR) for general lab operations; salary support as a Canada Research Chair (Tier 1) in functional proteomics; and from CITF and the Public Health Agency of Canada (PHAC) for assay calibration at Mount Sinai, all in support of the present manuscript. Dr. Gingras has had a contract with Providence Therapeutics (no consultation fees received), and has received grant funding from CIHR for several SARS-CoV-2 studies and from the Ontario Research Fund, outside of the present work. Dr. Gingras has served as the chair of the Institute Advisory Board of the CIHR Institute of Genetics and is a member and chair of the Human Health Therapeutics Division advisory board, National Research Council of Canada. Dr. Gingras is a member of the CITF working parties on testing and immunology, and is pillar lead of the Functional Genomics and Structure Function of CoVaRR-Net (all roles unpaid). Steven Drews reports receiving grants or contracts from CIHR and Alberta Innovates, consulting fees from Roche, support for attending meetings or travel from the Canadian Immunization Research Network and other support from Abbott. Jaspreet Jain reports receiving support from the CITF for the present manuscript. Prabhat Jha reports receiving grant support from the CITF for the Action to Beat Coronavirus study. Amanda Lang reports receiving funding from the CITF, in support of the present manuscript, for assay reagents and technologist salary. Dr. Lang has also received support from the CITF to attend a CITF meeting. Stephen Lee reports receiving funding from the CITF, in support of the present manuscript. Sheila O’Brien reports receiving payment (paid to Canadian Blood Services [CBS]) from the Government of Canada, and laboratory infrastructure from CBS, in support of the present manuscript. Chantale Pambrun reports receiving salary support from CBS, and study funding from PHAC. Olivia Oxlade is an employee of the CITF Secretariat. David Stephens reports receiving funds for a graduate student from the National Science and Engineering Research Council Emerging Infectious Disease Modelling, in support of the present manuscript. Hanna Swail reports receiving support from the CITF for the present manuscript. David Buckeridge reports receiving funding from PHAC, in support of the present manuscript. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts., Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography-mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men., Results: Higher concentrations of total testosterone (OR per one-unit increase in log 2  = 1.77, 95% CI = 1.38-2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21-2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22-20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27-2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33-0.68)., Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk., Impact and Implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Background: The association of sugar containing beverages (SCBs) with risk of breast, endometrial, ovarian and colorectal cancers is unclear. Therefore, we investigated these associations in the Canadian Study of Diet, Lifestyle, and Health., Methods: The study population comprised an age-stratified subcohort of 3185 women and 848, 161, 91 and 243 breast, endometrial, ovarian and colorectal cancer cases, respectively. We used Cox proportional hazards regression models modified for the case-cohort design to assess the associations of SCBs with risk of the aforementioned cancers., Results: Compared to SCB intake in the lowest tertile, SCB intake in the highest tertile was positively associated with endometrial cancer risk (HR T3 vs T1 = 1.58, 95 % CI = 1.08-2.33 and 1.78, 95 % CI = 1.12-2.81 for overall and Type 1 endometrial cancer, respectively) and ovarian cancer (HR T3 vs T1 = 1.76, 95 % CI: 1.09-2.83). Fruit juice intake was also positively associated with risk of Type 1endometrial (HR T3 vs T1 = 1.63, 95 % CI = 1.03-2.60). After excluding women with diabetes or cardiovascular diseases, we also observed sugar-sweetened beverages (SSBs) intake in the highest tertile was associated with higher risk of Type 1 endometrial cancer (HR T3 vs T1 = 1.65; 95 % CI: 1.03-2.64). None of the beverages was associated with risk of breast or colorectal cancer., Conclusion: We conclude that, in this cohort, relatively high SCB intake was associated with higher risk of endometrial and ovarian cancers, but not of breast or colorectal cancers. Our findings also suggest that relatively high SSB and fruit juice intake are associated with higher risk of Type 1 endometrial cancer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background and Aims: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts., Approach and Results: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log 2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05-1.89), but not HCC (OR = 1.12; 95% CI = 0.81-1.54)., Conclusions: This study provides evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk., (© 2020 by the American Association for the Study of Liver Diseases.)

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m 2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements., (© 2019 UICC.)

Background: Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC., Methods: We harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases)., Results: Hysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors., Conclusions: This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research., (©2020 American Association for Cancer Research.)

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (p het = 0.01), family history of ovarian cancer (p het = 0.02), body mass index (BMI; p het ≤ 0.04) and smoking (p het < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m 2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted., (© 2018 UICC.)

Few studies have explored the associations of thiamin, niacin and riboflavin with risk of cancer despite their role in potentially cancer-associated one-carbon metabolism. Using multivariable Cox proportional hazards regression models modified for the case-cohort design, we examined the associations of dietary intake of the above-mentioned B vitamins, as well as folate, and vitamins B6 and B12, with risk of the breast ( n = 922), endometrial ( n = 180), ovarian ( n = 104) and colorectal ( n = 266) cancers among age-stratified subcohorts of 3,185 women who were randomly selected from a cohort of 73,909 participants. None of the B-vitamins were associated with risk of breast or colorectal cancers. However, relatively high dietary intake of folate intake was inversely associated with risk of endometrial (HR q4 vs q1 : 0.52; 95% CI: 0.29-0.93) and ovarian (HR q3 vs q1 : 0.39; 95% CI: 0.19-0.80) cancers while relatively high dietary intake of vitamin B6 was inversely associated with ovarian cancer risk (HR q3 vs q1 : 0.49; 95% CI: 0.24-0.98). These findings suggest that dietary intake of folate may reduce risk of endometrial and ovarian cancers and dietary intake of vitamin B6 may reduce risk of ovarian cancer.

Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation., Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics., Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017., Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years., Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer., Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall., Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

Background: Although, biologically plausible evidence has implicated coffee, tea and caffeine with carcinogenesis, there is a paucity of data on their associations with risk of cancer among Canadian women. Hence, we assessed their associations with risk of breast, endometrial and ovarian cancers within this population., Methods: The study comprised a subcohort of 3185 women from a cohort of 39,532 female participants who completed self-administered lifestyle and dietary questionnaires at enrollment. During a median follow-up of approximately 12.2years, we ascertained 922, 180 and 104 breast, endometrial and ovarian cancer cases, respectively. We used Cox proportional hazards regression models modified for the case-cohort design to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the associations of coffee, tea and caffeine with risk of selected cancers., Results: Coffee, tea, and caffeine intake were not associated with overall risk of breast and ovarian cancers. There was, however, a tendency towards an increased risk of breast cancer with increasing levels of total coffee, caffeinated coffee and/or caffeine among premenopausal and normal weight women. Total coffee, caffeinated coffee, and caffeine were inversely associated with risk of endometrial cancer (HR per cup increase : 0.88; 95% CI: 0.79-0.95, HR per cup increase: 0.88; 95% CI: 0.80-0.96 and HR per 100mg increase: 0.93; 95% CI: 0.87-0.99, respectively)., Conclusion: Our findings suggest that coffee and/or caffeine may be associated with reduced risk of endometrial cancer but, probably, associated increased with risk of breast cancer among premenopausal or normal weight women. However, further studies are needed to confirm our findings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Several modifiable risk factors have been associated with risk of female cancers, but there is limited data regarding their combined effect on risk among Canadian women. Therefore, we assessed the joint association of modifiable risk factors, using a healthy lifestyle index (HLI) score, with risk of specific reproductive cancers., Method: This study included a subcohort of 3,185 of the 39,618 women, who participated in the Canadian Study of Diet, Lifestyle, and Health, and in whom 410, 177, and 100 postmenopausal breast, endometrial, and ovarian cancers, respectively, were ascertained. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression models modified for the case-cohort design., Results: Each unit increase in the HLI score was associated with 3% and 5% reductions in risk of postmenopausal breast cancer and endometrial cancer, respectively (HR 0.97; 95% CI 0.94-0.99 and HR 0.95; 95% CI 0.90-0.99, respectively). Compared to those with HLI score in the lowest category, those in the highest category had 30% and 46% reductions in risk of these cancers, respectively. The HLI score was not associated with altered risk of ovarian cancer., Conclusion: Our findings suggest that promoting a healthy lifestyle may aid in the primary prevention of postmenopausal breast and endometrial cancers.

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Introduction: While some studies have suggested associations between shift work and obesity, few have been population-based or considered multiple shift schedules. Since obesity is linked with several chronic health conditions, understanding which types of shift work influence obesity is important and additional work with more detailed exposure assessment of shift work is warranted., Methods: Using multivariate polytomous logistic regression, we investigated the associations between shift work (evening/night, rotating and other shift schedules) and overweight and obesity as measured by body mass index cross-sectionally among 1561 men. These men had previously participated as population controls in a prostate cancer case-control study conducted in northeastern Ontario from 1995 to 1999. We obtained information on work history (including shift work), height and weight from the existing self-reported questionnaire data., Results: We observed an association for ever (vs. never) having been employed in rotating shift work for both the overweight (OR [odds ratio] = 1.34; 95% CI [confidence interval]: 1.05-1.73) and obese (OR = 1.57; 95% CI: 1.12-2.21) groups. We also observed nonsignificant associations for ever (vs. never) having been employed in permanent evening/night shifts. In addition, we found a significant trend of increased risk for both overweight and obesity with increasing duration of rotating shift work., Conclusion: Both the positive association between rotating shift work and obesity and the suggested positive association for permanent evening/night shift work in this study are consistent with previous findings. Future population-based research that is able to build on our results while examining additional shift work characteristics will further clarify whether some shift patterns have a greater impact on obesity than others., Competing Interests: The authors have no conflicts of interest to declare.

Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality., Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information., Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04-1.10], BMI (per 5 kg/m2) = 1.06 [1.02-1.10], waist circumference (per 5 cm) = 1.03 [1.01-1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02-1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality., Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.

Background/objectives: It has been suggested that the association between shift work and chronic disease is mediated by an increase in obesity. However, investigations of the relationship between shift work and obesity reveal mixed findings. Using a recently developed exposure assessment tool, this study examined the association between shift work and obesity among Canadian women from two studies: a cohort of university alumni, and a population-based study., Methods: Self-administered questionnaire data were used from healthy, currently employed females in a population-based study, the Ontario Women's Diet and Health case-control study (n = 1611 controls), and from a subset of a of university alumni from the Canadian Study of Diet, Lifestyle, and Health (n = 1097) cohort study. Overweight was defined as BMI≥25 to <30, and obesity as BMI≥30. Reported occupation was converted to occupational codes and linked to a probability of shift work value derived from Survey of Labour and Income Dynamics data. Regular evenings, nights, or rotating work comprised shift work. Polytomous logistic regression estimated the association between probability of shift work, categorized as near nil, low, medium, and high probability of shift work, on overweight and obesity, controlling for detected confounders., Results: In the population-based sample, high probability of shift work was associated with obesity (reference = near nil probability of shift work, OR: 1.88, 95% CI: 1.01-3.51, p = 0.047). In the alumni cohort, no significant association was detected between shift work and overweight or obesity., Conclusions: As these analyses found a positive association between high probability of shift work exposure and obesity in a population-based sample, but not in an alumni cohort, it is suggested that the relationship between shift work and obesity is complex, and may be particularly susceptible to occupational and education-related factors within a given population.

Background: Evidence for a role of dietary risk factors in the cause of breast cancer has been inconsistent. The evaluation of overall dietary patterns instead of foods in isolation may better reflect the nature of true dietary exposure in a population., Objective: We used 2 cohort studies to identify and confirm associations between dietary patterns and breast cancer risk., Design: Dietary patterns were derived by using a principal components factor analysis in 1097 breast cancer cases and an age-stratified subcohort of 3320 women sampled from 39,532 female participants in the Canadian Study of Diet, Lifestyle and Health (CSDLH). We conducted a confirmatory factor analysis in 49,410 subjects in the National Breast Screening Study (NBSS) in whom 3659 cases of incident breast cancer developed. Cox regression models were used to estimate HRs for the association between derived dietary factors and risk of breast cancer in both cohorts., Results: The following 3 dietary factors were identified from the CSDLH: healthy, ethnic, and meat and potatoes. In the CSDLH, the healthy dietary pattern was associated with reduced risk of breast cancer (HR for high compared with low quintiles: 0.73; 95% CI: 0.58, 0.91; P-trend = 0.001), and the meat and potatoes dietary pattern was associated with increased risk in postmenopausal women only (HR for high compared with low quintiles: 1.26; 95% CI: 0.92, 1.73; P-trend = 0.043). In the NBSS, the association between the meat and potatoes pattern and postmenopausal breast cancer risk was confirmed (HR: 1.31; 95% CI: 0.98, 1.76; P-trend = 0.043), but there was no association between the healthy pattern and risk of breast cancer., Conclusion: Adherence to a plant-based diet that limits red meat intake may be associated with reduced risk of breast cancer, particularly in postmenopausal women., (© 2015 American Society for Nutrition.)

Background: Tobacco use has been implicated in the etiology of a large number of cancers, and there exists substantial biological plausibility that it could also be involved in breast carcinogenesis. Despite this, epidemiological evidence to date is inconsistent. The aim of this study was to investigate the role of active smoking and the risk of incident, invasive breast cancer using a prospective cohort of women from the Canadian Study of Diet, Lifestyle and Health., Methods: Using a case-cohort design, an age-stratified subcohort of 3314 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary questionnaires at baseline. A total of 1096 breast cancer cases were identified in the entire cohort (including 141 cases from the subcohort) by linkage to the Canadian Cancer Registry. Cox regression models were used to estimate hazard ratios for the association between the different smoking exposures and the risk of breast cancer, using a modification for the case-cohort design., Results: After carefully considering early-life exposures and potential confounders, we found no association between any smoking exposure and risk of breast cancer in this study (Hazard ratio=1.00, 95% confidence interval=0.87-1.17 for ever vs never smokers)., Conclusions: Although these results cannot rule out an association between smoking and breast cancer, they do agree with the current literature suggesting that, if an association does exist, it is relatively weak., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Some mental illnesses have been suggested to be associated with obesity, although results are somewhat inconsistent and research has focused mainly on depression., Methods: Associations between anxiety, depression, medications for these illnesses, and obesity were investigated cross-sectionally among women aged 25-74 (n = 3004) who participated as population controls in a cancer case-control study. Participants self-reported information on anxiety, depression, height, current weight and weight at age 25., Results: No association was observed between either anxiety or depression and either current overweight or obesity status. However, depressed women taking antidepressants were more likely to be obese [OR = 1.71 (95%CI  =  1.16-2.52) daily antidepressant use; OR = 1.89 (95% CI = 1.21-2.96) ever tricyclic antidepressant use]. In the full study sample consistent positive associations between anxiety, depression and obesity among women with a history of antidepressant use, and generally negative associations among women without, were suggested. Finally, weight gain was associated with history of anxiety [5-19 kg OR = 1.29 (95% CI = 1.06-1.57); ≥ 20 kg OR = 1.43 (95% CI = 1.08-1.88)] and depression [≥ 20 kg OR = 1.28 (95% CI = 0.99-1.65)]., Conclusions: These results suggest depression and anxiety may be associated with weight gain and antidepressant use may be associated with obesity.

Obesity, physical inactivity, and sedentary behavior, concomitants of the modern environment, are potentially modifiable breast cancer risk factors. This study investigated the association of anthropometric measurements, physical activity and sedentary behavior, with the risk of incident, invasive breast cancer using a prospective cohort of women enrolled in the Canadian Study of Diet, Lifestyle and Health. Using a case-cohort design, an age-stratified subcohort of 3,320 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary questionnaires at baseline. A total of 1,097 incident breast cancer cases were identified from the entire cohort via linkage to the Canadian Cancer Registry. Cox regression models, modified to account for the case-cohort design, were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between anthropometric characteristics, physical activity, and the risk of breast cancer. Weight gain as an adult was positively associated with risk of post-menopausal breast cancer, with a 6 % increase in risk for every 5 kg gained since age 20 (HR 1.06; 95 % CI 1.01-1.11). Women who exercised more than 30.9 metabolic equivalent task (MET) hours per week had a 21 % decreased risk of breast cancer compared to women who exercised less than 3 MET hours per week (HR  0.79; 95 % CI 0.62-1.00), most evident in pre-menopausal women (HR  0.62; 95 % CI 0.43-0.90). As obesity reaches epidemic proportions and sedentary lifestyles have become more prevalent in modern populations, programs targeting adult weight gain and promoting physical activity may be beneficial with respect to reducing breast cancer morbidity.

Botanical supplements are widely used and contain diverse ingredients, including isoflavones. Food-based isoflavones have been associated with reduced breast cancer risk. However, no study has comprehensively evaluated supplements identified by isoflavone content and breast cancer risk. Associations between ever use of 28 isoflavone supplements and breast cancer risk in Ontario, Canada were evaluated using cases (n = 3,101) identified in 2002-2003 from the Ontario Cancer Registry and controls (n = 3,471) identified through random digit dialing methods. Multivariate logistic regression was used to estimate age-adjusted odds ratio (AOR) and 95% confidence intervals (CI). Several individual supplements were associated with reduced breast cancer risk (e.g., Natural HRT; AOR = 0.39; 95% CI: 0.22, 0.69; n(users) = 58). Use of any isoflavone supplements was associated with reduced risk when ≥ 3 were ever used (AOR = 0.68; 95% CI: 0.54, 0.86; n(users) = 332; p(trend) = 0.008) or any was taken >5 years (AOR = 0.75; 95% CI: 0.60, 0.94; n(users) = 325; p(trend) = 0.01); high content supplements were consistently associated with reduced risk. Risk reduction was confined to postmenopausal breast cancer for both individual and combined supplements, and was strongest in the latter among high content users who ever took ≥ 3 supplements (AOR = 0.55; 95% CI: 0.38, 0.81; n(users) = 118; p(trend) = 0.04) or any >5 years (AOR = 0.47; 95% CI: 0.27, 0.81; n(users) = 60; p(trend) = 0.03). Associations did not differ by estrogen-progesterone tumor receptor status. In conclusion, isoflavone supplements were associated with decreased postmenopausal breast cancer risk. Further research to examine these novel findings is warranted, given the low supplement use and potential limitations of our results., (Copyright © 2012 UICC.)

Phytoestrogens are found in foods such as soy (isoflavones) and flaxseed (lignans), and certain botanical supplements. Their role in estrogen receptor positive (ER+) breast cancer recurrence and treatment is controversial, and it is unknown how this affects intake among patients. The Ontario Cancer Registry was used to identify 417 population-based breast cancer cases (mean time from diagnosis was 57 days). A questionnaire was mailed to determine intake of phytoestrogen foods and supplements in the last 2 mo, changes since diagnosis and differences by ER tumor status or hormonal treatment. Of 278 (67%) respondents, 56% consumed soy foods, 39% consumed isoflavone-rich foods (tofu, soybeans, soy milk, soy nuts), and 70% ate lignan-rich foods, including flaxseed (33%). Only soy milk, flaxseed, and flaxseed bread were commonly consumed more than once/wk. Few patients (4%) took isoflavone (soy, red clover, kudzu, licorice, isoflavones) or lignan/flaxseed supplements. Since diagnosis, 17% started or stopped soy foods (most stopped); this was more prevalent among those receiving hormonal treatment (20%; 95% confidence interval (CI): 14, 26) than not (6%; 95% CI: 1, 12). No other differences by ER status or hormonal treatment were observed. Research is needed to confirm this and to explore influencing factors.

Background: Prostate cancer is a disease with a complex etiology. Oxidative stress has been implicated in its pathogenesis; however, few prospective studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer., Methods: We investigated associations between an oxidative balance score, calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures, as well as each individual constituent of the score and risks of prostate cancer overall, and by clinical characteristics, in a case-cohort study (661 cases and 1864 subcohort) nested within the Canadian Study of Diet, Lifestyle, and Health cohort. Men in the lowest quintiles of each pro-oxidant exposure received a score of four (the highest score), while those in the highest quintile received a score of zero (the lowest score). In contrast, scoring for all anti-oxidants was performed in the opposite way. Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables, with higher values indicating a higher antioxidant status., Results: The average oxidative balance score was similar between prostate cancer cases and men in the subcohort: 25.2 and 25.3, respectively. There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios (HRs) of 1.00, 1.02, 1.03, 0.97 and 1.01 for increasing quintiles of the score (p-trend=0.71). There were also no associations for non-advanced or advanced disease, or when analysis was restricted to incident cases that arose after two years of follow-up (n=508). In general constituents of the score were not associated with prostate cancer, except for red meat intake (HR=1.44; 95%CI 1.06-1.95 comparing Q5 vs. Q1) and lycopene (HRs of 0.7-0.8 for increasing quintiles)., Conclusion: Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Recent studies suggest that vitamin D may be associated with reduced breast cancer risk, but most studies have evaluated only dietary vitamin D intake. The associations among ultraviolet radiation from sunlight, factors related to cutaneous vitamin D production, and breast cancer risk were evaluated in a population-based case-control study conducted in Ontario, Canada, between 2003 and 2004 (n = 3,101 cases and n = 3,471 controls). Time spent outdoors was associated with reduced breast cancer risk during 4 periods of life (>21 vs. ≤6 hours/week age-adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.60, 0.85 in the teenage years; OR = 0.64, 95% CI: 0.53, 0.76 in the 20s-30s; OR = 0.74, 95% CI: 0.61, 0.88 in the 40s-50s; and OR = 0.50, 95% CI: 0.37, 0.66 in the 60s-74 years). Sun protection practices and ultraviolet radiation were not associated with breast cancer risk. A combined solar vitamin D score, including all the variables related to vitamin D production, was significantly associated with reduced breast cancer risk. These associations were not confounded or modified by menopausal status, dietary vitamin D intake, or physical activity. This study suggests that factors suggestive of increased cutaneous production of vitamin D are associated with reduced breast cancer risk.

Diet plays an important role in the etiology of certain cancers, but there is limited evidence with regard to the association between diet and risk of endometrial cancer. Few prospective studies have investigated meat intake as a potential determinant of endometrial cancer risk. The objective of this study was to examine the association between endometrial cancer risk and total meat, red meat, processed meat, fish, and poultry intake. We conducted a case-cohort analysis within the Canadian Study of Diet, Lifestyle, and Health, a prospective cohort of 73 909 adults (39 614 women). Participants were recruited from 1992 to 1999, predominantly from three Canadian universities. We conducted a linkage with the Ontario Cancer Registry for the years 1992-2007 for the female cohort members, who resided in Ontario at the time of enrollment (n=26 024), to yield data on cancer incidence. The analytic sample was comprised of 107 incident cases and 1830 subcohort members, the latter being an age-stratified sample of the full cohort. A nonsignificant increase in the risk of endometrial cancer was associated with increased consumption of red meat [hazard ratio (HR)=1.62, 95% confidence intervals (CI)=0.86-3.08, for high vs. low intake; P trend=0.13)], processed meat (HR=1.45, 95% CI=0.80-2.61, for high vs. low intake; P trend=0.058), and all meat combined (HR=1.50, 95% CI=0.78-2.89, for high vs. low intake; P trend=0.14). No clear patterns were noted for poultry or fish. The results of this study, although based on a limited number of cases, suggest that relatively high meat intake may be associated with increased risk of endometrial cancer.

Background: Few studies have compared the prognostic value of tumor characteristics by type of breast cancer diagnosed in the interval between mammographic screenings with screen-detected breast cancers., Methods: We conducted a case-case study within the cohort of women (n = 431 480) in the Ontario Breast Screening Program who were aged 50 years and older and were screened between January 1, 1994, and December 31, 2002. Interval cancers, defined as breast cancers diagnosed within 24 months after a negative screening mammogram, were designated as true interval cancers (n = 288) or missed interval cancers (n = 87) if they were not identified at the time of screening but were identified in retrospect. Screen-detected breast cancers (n = 450) were selected to match interval cancers. Tumors were evaluated for stage, grade, mitotic index, histology, and expression of hormone receptors and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression., Results: Both true and missed interval cancers were of higher stage and grade than matched screen-detected breast cancers. However, true interval cancers had a higher mitotic index (OR = 3.13, 95% CI = 1.81 to 5.42), a higher percentage of nonductal histology (OR = 1.94, 95% CI = 1.05 to 3.59), and were more likely to be both estrogen receptor-negative (OR = 2.09, 95% CI = 1.32 to 3.30) and progesterone receptor-negative (OR = 2.49, 95% CI = 1.68 to 3.70) compared with matched screen-detected tumors., Conclusions: In this study, interval cancers were of higher stage and grade compared with screen-detected cancers. True interval cancers were more likely to have additional adverse prognostic features of estrogen and progesterone receptor negativity and nonductal morphology. The findings suggest a need for more sensitive screening modalities to detect true interval breast cancers and different approaches for early detection of fast-growing tumors.

Nonsteroidal antiinflammatory drugs (NSAIDs) may play a role in breast cancer prevention; however, breast cancer subtypes and lifestyle/host factors may influence their impact. During 1996-1998 in Canada, the authors examined the association between regular NSAID use (defined as daily use for at least 2 months) and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status, cigarette smoking exposure, and history of arthritis. Breast cancer cases (n = 3,125, including 1,600 ER+PR+ and 591 ER-PR-) and an age-matched, random sample of controls (n = 3,062) completed a general risk factor questionnaire, including detailed questions on prescription and nonprescription NSAID use. NSAID use was associated with reduced risk of breast cancer (odds ratio = 0.76, 95% confidence interval: 0.66, 0.88). The association was not significantly different for ER+PR+ (odds ratio = 0.71, 95% confidence interval: 0.60, 0.84) and ER-PR- cancers (odds ratio = 0.80, 95% confidence interval: 0.62, 1.03) (p(heterogeneity) = 0.66). The magnitude of the NSAID inverse association was similar for women with and without arthritis and across smoking strata (risk estimates ranged from 0.74 to 0.84). Breast cancer risk tended to decrease with increasing duration of NSAID use and was generally lowest for >or=7 years of use, and both acetylsalicylic acid and non-acetylsalicylic acid use were associated with reduced risks.

Background: Several epidemiologic studies have reported associations between fruit and vegetable intake and reduced risk of prostate cancer, but the findings are inconsistent and data on clinically relevant advanced prostate cancer are limited., Methods: We evaluated the association between prostate cancer risk and intake of fruits and vegetables in 1338 patients with prostate cancer among 29,361 men (average follow-up = 4.2 years) in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Participants completed both a general risk factor and a 137-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided., Results: Vegetable and fruit consumption was not related to prostate cancer risk overall; however, risk of extraprostatic prostate cancer (stage III or IV tumors) decreased with increasing vegetable intake (RR = 0.41, 95% CI = 0.22 to 0.74, for high versus low intake; P(trend) = .01). This association was mainly explained by intake of cruciferous vegetables (RR = 0.60, 95% CI = 0.36 to 0.98, for high versus low intake; P(trend) = .02), in particular, broccoli (RR = 0.55, 95% CI = 0.34 to 0.89, for >1 serving per week versus <1 serving per month; P(trend) = .02) and cauliflower (RR = 0.48, 95% CI = 0.25 to 0.89 for >1 serving per week versus <1 serving per month; P(trend) = .03). We found some evidence that risk of aggressive prostate cancer decreased with increasing spinach consumption, but the findings were not consistently statistically significant when restricted to extraprostatic disease., Conclusion: High intake of cruciferous vegetables, including broccoli and cauliflower, may be associated with reduced risk of aggressive prostate cancer, particularly extraprostatic disease.

Background: There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer., Methods: This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression., Results: A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined HRT., Conclusions: Information on mammographic density and HRT use should routinely be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening.

Objective: To examine how student beliefs about tobacco industry behaviour and marketing practices were related to occasional and regular smoking among 9th to 12th graders. These findings can provide insight for developing new tobacco industry denormalization messages for youth smoking populations., Methods: Cross-sectional data were collected from 14,767 grade 9 to 12 students attending 22 secondary schools within one Public Health Region of Canada using the Tobacco Module of School Heath Action, Planning and Evaluation System (SHAPES). Logistic regression analyses were used to determine if different beliefs about tobacco companies were able to differentiate never smokers from occasional smokers, and occasional smokers from regular smokers., Results: Occasional and regular smoking behaviour was significantly related to student beliefs about tobacco companies doing good things in the community, manipulating young people to think smoking is cool, advertising to youth, and using athletes and sports sponsorships to get young people to smoke., Conclusions: This study identified that beliefs about tobacco industry behaviour and marketing practices were related to youth smoking behaviour. In order to address the unique needs of smoking youth, discussions for future tobacco industry denormalization campaigns should consider messages tailored to focus on corporate social responsibility, sport and cultural event sponsorship and industry manipulation.

Background: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association., Methods: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up., Results: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95% CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (P(trend)=0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)=0.15; lasagna, P(trend)=0.02)., Conclusions: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration., ((Cancer Epidemiol Biomarkers Prev 2006;15(1):92-8).)

High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of > or =7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen.