Current opportunities to catalyze research in nutrition and cancer prevention – an interdisciplinary perspective

Cancer Research UK and Ludwig Cancer Research convened an inaugural international Cancer Prevention and Nutrition Conference in London on December 3–4, 2018. Much of the discussion focused on the need for systematic, interdisciplinary approaches to better understand the relationships of nutrition, exercise, obesity and metabolic dysfunction with cancer development. Scientists at the meeting underscored the importance of studying the temporal natural history of exposures that may cumulatively impact cancer risk later in life. A robust dialogue identified obesity as a major risk for cancer, and the food environment, especially high energy and low nutrient processed foods, as strong and prevalent risk factors for obesity. Further engagement highlighted challenges in the post-diagnostic setting, where similar opportunities to understand the complex interplay of nutrition, physical activity, and weight will inform better health outcomes. Going forward, holistic research approaches, encompassing insights from multiple disciplines and perspectives, will catalyze progress urgently needed to prevent cancer and improve public health

Insulin-like growth factor levels in cord blood, birth weight and breast cancer risk

Breast cancer incidence and birth weight are higher among Caucasian than Asian women, and birth size has been positively associated with breast cancer risk. Pregnancy hormone levels, however, have been generally lower in Caucasian than Asian women. We studied components of the insulin-like growth factor (IGF) system in cord blood from 92 singleton babies born in Boston, USA, and 110 born in Shanghai, China, in 1994–1995. Cord blood IGF-1 was significantly higher among Caucasian compared with Chinese babies (P<10−6). The opposite was noted for IGF-2 (P∼10−4). IGF-1 was significantly positively associated with birth weight and birth length in Boston, but not Shanghai. In contrast, stronger positive, though statistically non-significant, associations of IGF-2 with birth size were only evident in Shanghai. The associations of birth weight and birth length were positive and significant in taller women (for IGF-1 in Boston P∼0.003 and 0.03, respectively; for IGF-2 in Shanghai P∼0.05 and ∼0.04, respectively), among whom maternal anthropometry does not exercise strong constraints in foetal growth. The documentation of higher cord blood levels of IGF-1, a principal growth hormone that does not cross the placenta, among Caucasian than in Asian newborns is concordant with breast cancer incidence in these populations

Do people with risky behaviours participate in biomedical cohort studies?

BACKGROUND: Analysis was undertaken on data from randomly selected participants of a bio-medical cohort study to assess representativeness. The research hypotheses was that there was no difference in participation and non-participations in terms of health-related indicators (smoking, alcohol use, body mass index, physical activity, blood pressure and cholesterol readings and overall health status) and selected socio-demographics (age, sex, area of residence, education level, marital status and work status). METHODS: Randomly selected adults were recruited into a bio-medical representative cohort study based in the north western suburbs of the capital of South Australia – Adealide. Comparison data was obtained from cross-sectional surveys of randomly selected adults in the same age range and in the same region. The cohort participants were 4060 randomly selected adults (18+ years). RESULTS: There were no major differences between study participants and the comparison population in terms of current smoking status, body mass index, physical activity, overall health status and proportions with current high blood pressure and cholesterol readings. Significantly more people who reported a medium to very high alcohol risk participated in the study. There were some demographic differences with study participants more likely to be in the middle level of household income and education level. CONCLUSION: People with risky behaviours participated in this health study in the same proportions as people without these risk factors

Life-course body size and perimenopausal mammographic parenchymal patterns in the MRC 1946 British birth cohort

Dense mammographic parenchymal patterns are associated with an increased risk of breast cancer. Certain features of body size have been found to be associated with breast cancer risk, but less is known about their relation to breast density. We investigated the association of birth size, childhood growth and life-course changes in body size with Wolfe grade in 1298 perimenopausal women from a British cohort of women born in 1946. The cohort benefits from repeated measures of body size in childhood and adulthood. We obtained mammograms for 90% of women who at age 53 years reported having previously had a mammogram. We found no associations with birth weight or maximum attained height. Body mass index (BMI) at age 53 years and breast size were independently and inversely associated with Wolfe grade (P-value for trend <0.001 for both). Women who reached puberty later were at a greater odds of a higher Wolfe grade than women who had an earlier puberty (odds ratio associated with a 1 year delay in menarche 1.14, 95% CI: 1.01-1.27, adjusted for BMI and breast size at mammography). A higher BMI at any age during childhood or adult life was associated with a reduction in the odds of a higher Wolfe grade, after controlling for breast size and BMI at mammography, for example, standardised odds ratio for height at age 7 was 0.72 (95% CI: 0.64, 0.81). These findings reveal the importance of taking life-course changes in body size, and not just contemporaneous measures, into account when using mammographic density as an intermediate marker for risk of breast cancer

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Dietary patterns and risk of breast cancer

Background: Evidence is emerging that prudent/healthy dietary patterns might be associated with a reduced risk of breast cancer. Methods: Using data from the prospective Melbourne Collaborative Cohort Study, we applied principal factor analysis to 124 foods and beverages to identify dietary patterns and estimated their association with breast cancer risk overall and by tumour characteristics using Cox regression. Results: During an average of 14.1 years of follow-up of 20 967 women participants, 815 invasive breast cancers were diagnosed. Among the four dietary factors that we identified, only that characterised by high consumption of fruit and salad was associated with a reduced risk, with stronger associations observed for tumours not expressing oestrogen (ER) and progesterone receptors (PR). Compared with women in the lowest quintile of the factor score, the hazard ratio for women in the highest quintile was 0.92 (95% confidence interval (CI)=0.70-1.21; test for trend, P=0.5) for ER-positive or PR-positive tumours and 0.48 (95% CI=0.26-0.86; test for trend, P=0.002) for ER-negative and PR-negative tumours (test for homogeneity, P=0.01). Conclusion: Our study provides additional support for the hypothesis that a dietary pattern rich in fruit and salad might protect against invasive breast cancer and that the effect might be stronger for ER- and PR-negative tumours. © 2011 Cancer Research UK All rights reserved

Intrauterine environments and breast cancer risk: meta-analysis and systematic review

INTRODUCTION: Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS: We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS: We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION: Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood

Prior and Present Evidence: How Prior Experience Interacts with Present Information in a Perceptual Decision Making Task

Vibrotactile discrimination tasks have been used to examine decision making processes in the presence of perceptual uncertainty, induced by barely discernible frequency differences between paired stimuli or by the presence of embedded noise. One lesser known property of such tasks is that decisions made on a single trial may be biased by information from prior trials. An example is the time-order effect whereby the presentation order of paired stimuli may introduce differences in accuracy. Subjects perform better when the first stimulus lies between the second stimulus and the global mean of all stimuli on the judged dimension ("preferred" time-orders) compared to the alternative presentation order ("nonpreferred" time-orders). This has been conceptualised as a "drift" of the first stimulus representation towards the global mean of the stimulus-set (an internal standard). We describe the influence of prior information in relation to the more traditionally studied factors of interest in a classic discrimination task.Sixty subjects performed a vibrotactile discrimination task with different levels of uncertainty parametrically induced by increasing task difficulty, aperiodic stimulus noise, and changing the task instructions whilst maintaining identical stimulus properties (the "context").The time-order effect had a greater influence on task performance than two of the explicit factors-task difficulty and noise-but not context. The influence of prior information increased with the distance of the first stimulus from the global mean, suggesting that the "drift" velocity of the first stimulus towards the global mean representation was greater for these trials.Awareness of the time-order effect and prior information in general is essential when studying perceptual decision making tasks. Implicit mechanisms may have a greater influence than the explicit factors under study. It also affords valuable insights into basic mechanisms of information accumulation, storage, sensory weighting, and processing in neural circuits

Does socioeconomic disparity in cancer incidence vary across racial/ethnic groups?

Objective Very few studies have simultaneously examined incidence of the leading cancers in relation to socioeconomic status (SES) and race/ethnicity in populations including Hispanics and Asians. This study aims to describe SES disparity in cancer incidence within each of four major racial/ethnic groups (non-Hispanic white, black, Hispanic, and Asian/Pacific Islander) for five major cancer sites, including female breast cancer, colorectal cancer, cervical cancer, lung cancer, and prostate cancer. Methods Invasive cancers of the five major sites diagnosed from 1998 to 2002 (n = 376,158) in California were included in the study. Composite area-based SES measures were used to quantify SES level and to calculate cancer incidence rates stratified by SES. Relative index of inequality (RII) was generated to measure SES gradient of cancer incidence within each racial/ethnic group. Results Significant variations were detected in SES disparities across the racial/ethnic groups for all five major cancer sites. Female breast cancer and prostate cancer incidence increased with increased SES in all groups, with the trend strongest among Hispanics. Incidence of cervical cancer increased with decreased SES, with the largest gradient among non-Hispanic white women. Lung cancer incidence increased with decreased SES with the exception of Hispanic men and women, for whom SES gradient was in the opposite direction. For colorectal cancer, higher incidence was associated with lower SES in non-Hispanic whites but with higher SES in Hispanics and Asian/Pacific Islander women. Conclusions Examining SES disparity stratified by race/ethnicity enhances our understanding of the complex relationships between cancer incidence, SES, and race/ethnicity

Does diet affect breast cancer risk?

The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol is the best established dietary risk factor, probably by increasing endogenous estrogen levels. Hypotheses relating diet during youth to risk decades later will be difficult to test. Nevertheless, available evidence is strong that breast cancer risk can be reduced by avoiding weight gain during adult years, and by limiting alcohol consumption