Background Excess body mass index (BMI) is associated with increased risk of cancer. To inform public health policyand future research, we estimated the global burden of cancer attributable to excess BMI. Methods Population attributable fractions (PAFs) were derived using relative risks and BMI estimates in adults by age, sex and country. Assuming a10-year lag-period, PAFs were calculated using BMI estimates in 2002. GLOBOCAN2012 was used to compute numbers of new cancer cases attributable to excess BMI. In an alternative scenario, we computed the proportion of potentially avoidable cancers assuming that populations maintained their BMI-level observed in 1982. Secondary analyses were performed to test the model and estimate the impactof hormone replacement therapy (HRT) and smoking. Findings Worldwide, we estimated that 481,000 or 3·6% of all new cancer cases in 2012 were attributable to excess BMI. PAFs were greater in women compared with men (5·4% versus 1·9%). The burden was concentrated in countries with very high and high human development index (HDI, PAF: 5·3% and 4·8%) compared with countries with moderate and low HDI (PAF: 1·6% and 1·0%). Corpus uteri, post-menopausal breast and colon cancers accounted for approximately two-thirds (64%) of excess BMI attributable cancers. One fourth (~118,000) of all cases related to excess BMI in 2012 could be attributed to the rising BMI since 1982. Interpretation These findings further underpin the need for a global effort to abate the rising trends in population-level excess weight. Assuming that the relationship between excess BMI and cancer is causal and the current pattern of population weight gain continues, this will likely augment the future burden of cancer. Funding World Cancer Research Fund, Marie Currie Fellowship, the National Health and Medical Research Council Australia and US NIH.

Objective: To measure the relative risks of adenocarcinomas of the oesophagus and gastro-oesophageal junction associated with measures of obesity, and their interactions with age, sex, gastro-oesophageal reflux symptoms and smoking. Design and setting: Population-based case-control study in Australia. Patients: Patients with adenocarcinomas of the oesophagus (n = 367) or gastro-oesophageal junction (n = 426) were compared with control participants (n = 1580) sampled from a population register. Main outcome measure: Relative risk of adenocarcinoma of the oesophagus or gastro-oesophageal junction. Results: Risks of oesophageal adenocarcinoma increased monotonically with body mass index (BMI) (p trend ,0.001). Highest risks were seen for BMI >40 kg/m 2 (odds ratio (OR) = 6.1, 95% CI 2.7 to 13.6) compared with ''healthy'' BMI (18.5-24.9 kg/m 2 ). Adjustment for gastro-oesophageal reflux and other factors modestly attenuated risks. Risks associated with obesity were substantially higher among men (OR = 2.6, 95% CI 1.8 to 3.9) than women (OR = 1.4, 95% CI 0.5 to 3.5), and among those aged ,50 years (OR = 7.5, 95% CI 1.7 to 33.0) than those aged >50 years (OR = 2.2, 95% CI 1.5 to 3.1). Obese people with frequent symptoms of gastrooesophageal reflux had significantly higher risks (OR = 16.5, 95% CI 8.9 to 30.6) than people with obesity but no reflux (OR = 2.2, 95% CI 1.1 to 4.3) or reflux but no obesity (OR = 5.6, 95% 2.8 to 11.3), consistent with a synergistic interaction between these factors. Similar associations, but of smaller magnitude, were seen for gastro-oesophageal junction adenocarcinomas. Conclusions: Obesity increases the risk of oesophageal adenocarcinoma independently of other factors, particularly among men. From a clinical perspective, these data suggest that patients with obesity and frequent symptoms of gastro-oesophageal reflux are at especially increased risk of adenocarcinoma.

Background Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. MethodsWe harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause). FindingsOverall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4•3%) had a first nonfatal cardiovascular disease event after menopause, of whom 9369 (3•1%) had coronary heart disease and 4338 (1•4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1•55, 95% CI 1•38-1•73; p<0•0001), early menopause (age 40-44 years; 1•30, 1•22-1•39; p<0•0001), and relatively early menopause (age 45-49 years; 1•12, 1•07-1•18; p<0•0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0•0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1•88, 1•62-2•20; p<0•0001) and early menopause (1•40, 1•27-1•54; p<0•0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older.Interpretation Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as ...