Breast cancer risk and prevention in 2024: An overview from the Breast Cancer UK - Breast Cancer Prevention Conference.

The Breast Cancer UK-Breast Cancer Prevention Conference addressed risk from environmental pollutants and health behaviour-related breast-cancer risk. Epidemiological studies examining individual chemicals and breast cancer risk have produced inconclusive results including endocrine disrupting chemicals (EDCs) Bisphenol A, per- and polyfluorinated alkyl substances as well as aluminium. However, laboratory studies have shown that multiple EDCs, can work together to exhibit effects, even when combined at levels that alone are ineffective. The TEXB-α/ß assay measures total estrogenic load, and studies have provided evidence of a link between multiple-chemical exposures and breast cancer. However, prospective studies using TEXB-α/ß are needed to establish a causative link. There is also a need to assess real-life exposure to environmental-chemical mixtures during pregnancy, and their potential involvement in programming adverse foetal health outcomes in later life. Higher rates of breast cancer have occurred alongside increases in potentially-modifiable risk factors such as obesity. Increasing body-mass index is associated with increased risk of developing postmenopausal breast cancer, but with decreased risk of premenopausal breast cancer. In contrast, lower rates of breast cancer in Asian compared to Western populations have been linked to soya/isoflavone consumption. Risk is decreased by breastfeeding, which is in addition to the decrease in risk observed for each birth and a young first-birth. Risk is lower in those with higher levels of self-reported physical activity. Current evidence suggests breast-cancer survivors should also avoid weight gain, be physically active, and eat a healthy diet for overall health. A broad scientific perspective on breast cancer risk requires focus on both environmental exposure to chemicals and health behaviour-related risk. Research into chemical exposure needs to focus on chemical mixtures and prospective epidemiological studies in order to test the effects on breast cancer risk. Behaviour-related research needs to focus on implementation as well as deeper understanding of the mechanisms of cancer prevention.

Adiposity assessed close to diagnosis and prostate cancer prognosis in the EPIC study.

BACKGROUND: Adiposity has been characterized as a modifiable risk factor for prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, must be better understood, and more evidence is needed to facilitate the development of lifestyle guidance for patients with prostate cancer. METHODS: We investigated the associations between adiposity indices close to prostate cancer diagnosis (up to 2 years before or up to 5 years after diagnosis) and mortality in 1968 men of the European Prospective Investigation into Cancer and Nutrition cohort. Men were followed up for a median of 9.5 years. Cox proportional hazards models were adjusted for age and year of diagnosis, disease stage and grade, and smoking history and stratified by country. RESULTS: Each 5-unit increment in prediagnosis or postdiagnosis body mass index combined was associated with a 30% higher rate of all-cause mortality and a 49% higher rate of prostate cancer-specific mortality. Similarly, each 5-unit increment in prediagnosis body mass index was associated with a 35% higher rate of all-cause mortality and a 51% higher rate of prostate cancer-specific mortality. The associations were less strong for postdiagnosis body mass index, with a lower number of men in analyses. Less clear positive associations were shown for waist circumference, hip circumference, and waist to hip ratio, but data were limited. CONCLUSIONS: Elevated levels of adiposity close to prostate cancer diagnosis could lead to higher risk of mortality; therefore, men are encouraged to maintain a healthy weight. Additional research is needed to confirm whether excessive adiposity after prostate cancer diagnosis could worsen prognosis.

Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Post-diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification.

Association between adiposity after diagnosis of prostate cancer and mortality: systematic review and meta-analysis.

Objective: To explore the associations between adiposity indices, assessed at or after a diagnosis of prostate cancer, and mortality. Design: Systematic review and meta-analysis. Data sources: PubMed and Embase, from inception to 16 November 2022. Eligibility criteria for selecting studies: Cohort studies or randomised controlled trials of men with a diagnosis of prostate cancer that investigated the associations between adiposity (body mass index, waist and hip circumference, waist-to-hip ratio, and subcutaneous and visceral adipose tissue) after diagnosis and mortality outcomes. A modified version of the risk of bias for nutrition observational studies tool was used to assess risk of bias. Results: 79 studies were identified that investigated adiposity indices after a diagnosis of prostate cancer in relation to mortality. No randomised controlled trials were found. A non-linear dose-response meta-analysis indicated a J shaped association between body mass index and all cause mortality (33 910 men, 11 095 deaths, 17 studies). The highest rate of all cause mortality was found at the lowest and upper range of the distribution: 11-23% higher rate for a body mass index of 17-21 and 4-43% higher rate for a body mass index of 30-40. The association between body mass index and mortality specific to prostate cancer was flat until body mass index reached 26-27, and then increased linearly by 8-66% for a body mass index of 30-40 (33 137 men, 2947 deaths, 13 studies), but the 95% confidence intervals were wide. These associations did not differ in most predefined subgroups by study design, number of deaths, anthropometric assessment, follow-up time, geographical location, prostate cancer risk group, and adjustment variables. No associations were found in meta-analyses between 10 cm increases in waist circumference and all cause mortality or mortality specific to prostate cancer, but only three studies were available. The few studies with data on change in weight, waist-to-hip ratio, and subcutaneous and visceral adipose tissue reported conflicting results. Conclusions: This review suggests that patients with prostate cancer might benefit from maintaining a healthy weight and avoiding obesity. Future studies should investigate adiposity across different stages of cancer survivorship and use various parameters for distribution of adipose tissue. Systematic review registration: Open Science Framework https://osf.io/qp3c4.

Lifestyle Score and Risk of Hypertension in the Airwave Health Monitoring Study of British Police Force Employees.

BACKGROUND: Evidence suggest that promoting a combination of healthy lifestyle behaviors instead of exclusively focusing on a single behavior may have a greater impact on blood pressure (BP). We aimed to evaluate lifestyle factors and their impact on the risk of hypertension and BP. METHODS: We analyzed cross-sectional health-screening data from the Airwave Health Monitoring Study of 40,462 British police force staff. A basic lifestyle-score including waist-circumference, smoking and serum total cholesterol was calculated, with a greater value indicating a better lifestyle. Individual/combined scores of other lifestyle factors (sleep duration, physical activity, alcohol intake, and diet quality) were also developed. RESULTS: A 1-point higher basic lifestyle-score was associated with a lower systolic BP (SBP; -2.05 mmHg, 95%CI: -2.15, -1.95); diastolic BP (DBP; -1.98 mmHg, 95%CI: -2.05, -1.91) and was inversely associated with risk of hypertension. Combined scores of other factors showed attenuated but significant associations with the addition of sleep, physical activity, and diet quality to the basic lifestyle-score; however, alcohol intake did not further attenuate results. CONCLUSIONS: Modifiable intermediary factors have a stronger contribution to BP, namely, waist-circumference and cholesterol levels and factors that may directly influence them, such as diet, physical activity and sleep. Observed findings suggest that alcohol is a confounder in the BP-lifestyle score relation.

Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis.

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2  = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.

Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.

Physical Activity and Health-Related Quality of Life in Women With Breast Cancer: A Meta-Analysis.

BACKGROUND: Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund-American Institute for Cancer Research Continuous Update Project. METHODS: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. RESULTS: A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy-General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. CONCLUSION: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites.

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.

World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk.

PURPOSE: The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. METHODS: Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. RESULTS: One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18-30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR- breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. CONCLUSION: Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed.

Height and body fatness and colorectal cancer risk: an update of the WCRF-AICR systematic review of published prospective studies.

PURPOSE: There is no published dose-response meta-analysis on the association between height and colorectal cancer risk (CRC) by sex and anatomical sub-site. We conducted a meta-analysis of prospective studies on the association between height and CRC risk with subgroup analysis and updated evidence on the association between body fatness and CRC risk. METHODS: PubMed and several other databases were searched up to November 2016. A random effects model was used to calculate dose-response summary relative risks (RR's). RESULTS: 47 studies were included in the meta-analyses including 50,936 cases among 7,393,510 participants. The findings support the existing evidence regarding a positive association of height, general and abdominal body fatness and CRC risk. The summary RR were 1.04 [95% (CI)1.02-1.05, I² = 91%] per 5 cm increase in height, 1.02 [95% (CI)1.01-1.02, I² = 0%] per 5 kg increase in weight, 1.06 [95% (CI)1.04-1.07, I² = 83%] per 5 kg/m2 increase in BMI, 1.02 [95% (CI)1.02-1.03, I² = 4%] per 10 cm increase in waist circumference, 1.03 [95% (CI)1.01-1.05, I² = 16%] per 0.1 unit increase in waist to hip ratio. The significant association for height and CRC risk was similar in men and women. The significant association for BMI and CRC risk was stronger in men than in women. CONCLUSION: The positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology. Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women.

Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

Context: The investigation of dose-response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. Objective: A systematic review and dose-response meta-analyses was conducted to investigate these associations. Data Sources: As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Study Selection: Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Data Extraction: Two investigators independently extracted data from included studies. Results: Random-effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta-regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00-1.07) per 10 units/d for glycemic index, 1.01 (0.98-1.04) per 50 units/d for glycemic load, and 1.00 (0.96-1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02-1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen-negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08-1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02-1.25). No differences in BMI were detected. Conclusions: Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations between carbohydrate intake, glycemic index, glycemic load, and breast cancer.

An update of the WCRF/AICR systematic literature review on esophageal and gastric cancers and citrus fruits intake.

PURPOSE: The 2007 World Cancer Research Fund/American Institute for Cancer Research expert report concluded that foods containing vitamin C probably protect against esophageal cancer and fruits probably protect against gastric cancer. Most of the previous evidence was from case-control studies, which may be affected by recall and selection biases. More recently, several cohort studies have examined these associations. We conducted a systematic literature review of prospective studies on citrus fruits intake and risk of esophageal and gastric cancers. METHODS: PubMed was searched for studies published until 1 March 2016. We calculated summary relative risks and 95 % confidence intervals (95 % CI) using random-effects models. RESULTS: With each 100 g/day increase of citrus fruits intake, a marginally significant decreased risk of esophageal cancer was observed (summary RR 0.86, 95 % CI 0.74-1.00, 1,057 cases, six studies). The associations were similar for squamous cell carcinoma (RR 0.87, 95 % CI 0.69-1.08, three studies) and esophageal adenocarcinoma (RR 0.93, 95 % CI 0.78-1.11, three studies). For gastric cancer, the nonsignificant inverse association was observed for gastric cardia cancer (RR 0.75, 95 % CI 0.55-1.01, three studies), but not for gastric non-cardia cancer (RR 1.02, 95 % CI 0.90-1.16, four studies). Consistent summary inverse associations were observed when comparing the highest with lowest intake, with statistically significant associations for esophageal (RR 0.77, 95 % CI 0.64-0.91, seven studies) and gastric cardia cancers (RR 0.62, 95 % CI 0.39-0.99, three studies). CONCLUSIONS: Citrus fruits may decrease the risk of esophageal and gastric cardia cancers, but further studies are needed.

Circulating C-Reactive Protein and Breast Cancer Risk-Systematic Literature Review and Meta-analysis of Prospective Cohort Studies.

We conducted a systematic literature review to explore the association between circulating C-reactive protein (CRP), a low-grade inflammation biomarker, and breast cancer risk. Relevant prospective studies in women were identified in PubMed and Web of Science until February 2015. Random-effects dose-response meta-analysis was conducted, overall and in postmenopausal women. Twelve out of 15 studies identified were included in the meta-analysis on any breast cancers (3,522 cases; 69,610 women) and nine on postmenopausal breast cancer (2,516 cases; 36,847 women). For each doubling of CRP concentration, a 7% [95% confidence interval (CI), 2%-12%] and 6% (95% CI, 1%-11%) increased risk was observed (I(2) = 47% and 32%; Pheterogeneity = 0.04 and 0.17), respectively. The association was linear over most of the range of CRP concentrations. Positive associations remained in the studies that examined the exclusion of early years of follow-up. Associations were attenuated in studies adjusted for lifestyle factors, which partly explained the significant heterogeneity between studies in the overall analysis. On average, the associations in studies adjusted or not adjusted for body mass index were similar. Low-grade inflammation may have a role in breast cancer development. Additional prospective studies are needed to better understand confounding and effect modification from lifestyle factors.

Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies.

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95% CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0.97 (95% CI 0.94, 1.00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0.86 (95% CI 0.69, 1.09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47%, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0.94 (95% CI 0.89, 0.99), seven studies, I2= 78%; highest v. lowest HR 0.82 (95% CI 0.66, 1.02), nine studies, I2= 81%) and HDL-C (dose-response HR 0.81 (95% CI 0.65, 1.02), five studies, I2= 30 %; highest v. lowest HR 0.82 (95% CI 0.69, 0.98), five studies, I2= 0%). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.