SummaryBackgroundOverweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up.MethodsOf 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m2.FindingsAll-cause mortality was minimal at 20·0–25·0 kg/m2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m2; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m2), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m2; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m2; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m2). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m2) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m2) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m2) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m2, mortality increased approximately log-linearly with BMI; the HR per 5 kg/m2 units higher BMI was 1·39 (1·34–1·43) in Europe, 1·29 (1·26–1·32) in North America, 1·39 (1·34–1·44) in east Asia, and 1·31 (1·27–1·35) in Australia and New Zealand. This HR per 5 kg/m2 units higher BMI (for BMI over 25 kg/m2) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years vs 1·21, 1·17–1·25, for BMI measured at 70–89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46–1·56, vs 1·30, 1·26–1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI.InterpretationThe associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations.FundingUK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.

Objective To examine the relation between body mass index (kg/m 2 ) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality.

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SummaryBackgroundWomen born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life. Hence, only in the 21st century can we observe directly the full effects of prolonged smoking, and of prolonged cessation, on mortality among women in the UK.MethodsFor this prospective study, 1·3 million UK women were recruited in 1996–2001 and resurveyed postally about 3 and 8 years later. All were followed to Jan 1, 2011, through national mortality records (mean 12 woman-years, SD 2). Participants were asked at entry whether they were current or ex-smokers, and how many cigarettes they currently smoked. Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking. We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers.FindingsAfter excluding 0·1 million women with previous disease, 1·2 million women remained, with median birth year 1943 (IQR 1938–46) and age 55 years (IQR 52–60). Overall, 6% (66 489/1 180 652) died, at mean age 65 years (SD 6). At baseline, 20% (232 461) were current smokers, 28% (328 417) were ex-smokers, and 52% (619 774) were never-smokers. For 12-year mortality, those smoking at baseline had a mortality rate ratio of 2·76 (95% CI 2·71–2·81) compared with never-smokers, even though 44% (37 240/85 256) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking. Mortality was tripled, largely irrespective of age, in those still smoking at the 3-year resurvey (rate ratio 2·97, 2·88–3·07). Even for women smoking fewer than ten cigarettes per day at baseline, 12-year mortality was doubled (rate ratio 1·98, 1·91–2·04). Of the 30 most common causes of death, 23 were increased significantly in smokers; for lung cancer, the rate ratio was 21·4 (19·7–23·2). The excess mortality among smokers (in comparison with never-smokers) was mainly from diseases that, like lung cancer, can be caused by smoking. Among ex-smokers who had stopped permanently at ages 25–34 years or at ages 35–44 years, the respective relative risks were 1·05 (95% CI 1·00–1·11) and 1·20 (1·14–1·26) for all-cause mortality and 1·84 (1·45–2·34) and 3·34 (2·76–4·03) for lung cancer mortality. Thus, although some excess mortality remains among these long-term ex-smokers, it is only 3% and 10% of the excess mortality among continuing smokers. If combined with 2010 UK national death rates, tripled mortality rates among smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference.InterpretationAmong UK women, two-thirds of all deaths of smokers in their 50s, 60s, and 70s are caused by smoking; smokers lose at least 10 years of lifespan. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater. Stopping before a...

Low to moderate alcohol consumption in women increases the risk of certain cancers. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the esophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75.

Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women.

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort‐wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow‐up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size–breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend ≤ 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00–1.16) in premenopausal and 1.10 (95% CI 1.05–1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist–hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer. © 2004 Wiley‐Liss, Inc.

SummaryBackgroundEpidemiological studies have shown that taller people are at increased risk of cancer, but it is unclear if height-associated risks vary by cancer site, or by other factors such as smoking and socioeconomic status. Our aim was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors.MethodsInformation on height and other factors relevant for cancer was obtained in 1996–2001 for middle-aged women without previous cancer who were followed up for cancer incidence. We used Cox regression models to calculate adjusted relative risks (RRs) per 10 cm increase in measured height for total incident cancer and for 17 specific cancer sites, taking attained age as the underlying time variable. We also did a meta-analysis of published results from prospective studies of total cancer risk in relation to height.Findings1 297 124 women included in our analysis were followed up for a total of 11·7 million person-years (median 9·4 years per woman, IQR 8·4–10·2), during which time 97 376 incident cancers occurred. The RR for total cancer was of 1·16 (95% CI 1·14–1·17; p<0·0001) for every 10 cm increase in height. Risk increased for 15 of the 17 cancer sites we assessed, and was statistically significant for ten sites: colon (RR per 10 cm increase in height 1·25, 95% CI 1·19–1·30), rectum (1·14, 1·07–1·22), malignant melanoma (1·32, 1·24–1·40), breast (1·17, 1·15–1·19), endometrium (1·19, 1·13–1·24), ovary (1·17, 1·11–1·23), kidney (1·29, 1·19–1·41), CNS (1·20, 1·12–1·29), non-Hodgkin lymphoma (1·21, 1·14–1·29), and leukaemia (1·26, 1·15–1·38). The increase in total cancer RR per 10 cm increase in height did not vary significantly by socioeconomic status or by ten other personal characteristics we assessed, but was significantly lower in current than in never smokers (p<0·0001). In current smokers, smoking-related cancers were not as strongly related to height as were other cancers (RR per 10 cm increase in height 1·05, 95% CI 1·01–1·09, and 1·17, 1·13–1·22, respectively; p=0·0004). In a meta-analysis of our study and ten other prospective studies, height-associated RRs for total cancer showed little variation across Europe, North America, Australasia, and Asia.InterpretationCancer incidence increases with increasing adult height for most cancer sites. The relation between height and total cancer RR is similar in different populations.FundingCancer Research UK and the UK Medical Research Council.