Background: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers.

Methods: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects.

Findings: 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56—1·69; p<0·0001), gallbladder (1·31, 1·12—1·52; p<0·0001), kidney (1·25, 1·17—1·33; p<0·0001), cervix (1·10, 1·03—1·17; p=0·00035), thyroid (1·09, 1·00—1·19; p=0·0088), and leukaemia (1·09, 1·05—1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12—1·27), colon (1·10, 1·07—1·13), ovarian (1·09, 1.04—1.14), and postmenopausal breast cancers (1·05, 1·03—1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95—1·00; premenopausal breast cancer 0·89, 0·86—0·92) and in never-smokers (prostate 0·96, 0·93—0·99; premenopausal breast cancer 0·89, 0·85—0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93—1·05; oral cavity 1·07, 0·91—1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI.

Interpretation: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups.

Background: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups.

Interpretation: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.

Conclusions: Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.

Obesity is or may be a cause of a number of cancers... Maintenance of a healthy weight throughout life may be
one of the most important ways to protect against cancer.
This will also protect against a number of other common
chronic diseases.

> Background: High body-mass index (BMI; defined as 25 kg/m2 or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012.

> Methods: In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking.

> Findings: Worldwide, we estimate that 481 000 or 3·6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5·4% vs 1·9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5·3% and 4·8%, respectively) than in those with moderate (1·6%) and low HDIs (1·0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63·6% of cancers attributable to high BMI. A quarter (about 118 000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982.

> Interpretation: These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer.

Citerank: (21) 348776A profound impact on the health of the populationObesity is responsible for more than 9,000 premature deaths each year in England, reduces life expectancy on average by nine years, and is a major risk factor in wide range of serious health problems including Type 2 diabetes (5 x), cancer (3 x the risk of colon cancer), and heart disease (2.5 x).57DE7179, 352344Increased risk of musculoskeletal disabilityRaised body weight puts strain on the body's joints, especially the knees, increasing the risk of osteoarthritis (degeneration of cartilage and underlying bone within a joint). There is also an increased risk of low back pain.57DE7179, 352349Increased risk of heart diseaseRaised BMI increases the risk of hypertension (high blood pressure), which is itself a risk factor for coronary heart disease and stroke and can contribute to other conditions such as renal failure. The risk of coronary heart disease (including heart attacks and heart failure) and stroke are both substantially increased. Risks of deep vein thrombosis and pulmonary embolism are also increased.57DE7179, 352351Increased risk of Type 2 diabetes Obesity substantially raises the risk of Type 2 diabetes—with excess body fat estimated to underlie almost two-thirds of cases of diabetes in men and three quarters of cases in women—and people at risk of diabetes can cut their chances of getting diabetes by 60% if they lose between 5% and 7% of their body weight. Worldwide, the number of people with diabetes has tripled since 1985. [2]57DE7179, 352353Increased risk of reproductive and urological problemsObesity is associated with greater risk of stress incontinence in women. Obese women are at greater risk of menstrual abnormalities, polycystic ovarian syndrome and infertility. Obese men are at higher risk of erectile dysfunction. Maternal obesity is associated with health risks for both the mother and the child and after pregnancy.57DE7179, 352354Increased risk of sleep apnoea and asthmaOverweight and obese people are at increased risk of sleep apnoea (interruptions to breathing while asleep) and other respiratory problems such as asthma.57DE7179, 352355Increased risk of non-alcoholic fatty liver diseaseThe term ‘non-alcoholic fatty liver disease’ (NAFLD) refers to a range of conditions resulting from the accumulation of fat in cells inside the liver. It is one of the commonest forms of liver disease in the UK. If left untreated, it may progress to severe forms such as non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It has also been linked to liver cancer. 57DE7179, 352356Increased risk of gastrointestinal diseaseObesity is associated with: increased risk of gastro-oesophageal reflux and increased risk of gall stones.57DE7179, 352357Increased risk of psychological and social problemsThere are bi-directional associations between mental health problems and obesity, with levels of obesity, gender, age and socioeconomic status being key risk factors. Overweight and obese people can suffer from stress, low self-esteem, social disadvantage, depression and reduced libido.57DE7179, 3523581 in 5 UK children aged 10-11 are obeseThe National Child Measurement Programme (NCMP) figures for 2013/14, show that 19.1% of children in Year 6 (aged 10-11) were obese and a further 14.4% were overweight. Obese children and adolescents are at an increased risk of developing various health problems—such as asthma, cardiovascular disease and type 2 diabetes (as well as low self-esteem and depression)—and are also more likely to become obese adults.648CC79C, 399974A profound impact on the health of the populationObesity is responsible for more than 9,000 premature deaths each year in England, reduces life expectancy on average by nine years, and is a major risk factor in wide range of serious health problems including Type 2 diabetes (5 x), cancer (3 x the risk of colon cancer), and heart disease (2.5 x).57DE7179, 3999751 in 5 UK children aged 10-11 are obeseThe National Child Measurement Programme (NCMP) figures for 2013/14, show that 19.1% of children in Year 6 (aged 10-11) were obese and a further 14.4% were overweight. Obese children and adolescents are at an increased risk of developing various health problems—such as asthma, cardiovascular disease and type 2 diabetes (as well as low self-esteem and depression)—and are also more likely to become obese adults.648CC79C, 399983Increased risk of several cancersThe risk of several cancers is higher in obese people, including endometrial, breast and colon cancers. BMI is associated with cancer risk, with substantial population-level effects (although the heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups).57DE7179, 399985Increased risk of musculoskeletal disabilityRaised body weight puts strain on the body's joints, especially the knees, increasing the risk of osteoarthritis (degeneration of cartilage and underlying bone within a joint). There is also an increased risk of low back pain.57DE7179, 399986Increased risk of heart diseaseRaised BMI increases the risk of hypertension (high blood pressure), which is itself a risk factor for coronary heart disease and stroke and can contribute to other conditions such as renal failure. The risk of coronary heart disease (including heart attacks and heart failure) and stroke are both substantially increased. Risks of deep vein thrombosis and pulmonary embolism are also increased.57DE7179, 399987Increased risk of Type 2 diabetes Obesity substantially raises the risk of Type 2 diabetes—with excess body fat estimated to underly almost two-thirds of cases of diabetes in men and three quarters of cases in women—and people at risk of diabetes can cut their chances of getting diabetes by 60% if they lose between 5% and 7% of their body weight. Worldwide, the number of people with diabetes has tripled since 1985.57DE7179, 399988Increased risk of reproductive and urological problemsObesity is associated with greater risk of stress incontinence in women. Obese women are at greater risk of menstrual abnormalities, polycystic ovarian syndrome and infertility. Obese men are at higher risk of erectile dysfunction. Maternal obesity is associated with health risks for both the mother and the child and after pregnancy.57DE7179, 399989Increased risk of sleep apnoea and asthmaOverweight and obese people are at increased risk of sleep apnoea (interruptions to breathing while asleep) and other respiratory problems such as asthma.57DE7179, 399990Increased risk of non-alcoholic fatty liver diseaseThe term ‘non-alcoholic fatty liver disease’ (NAFLD) refers to a range of conditions resulting from the accumulation of fat in cells inside the liver. It is one of the commonest forms of liver disease in the UK. If left untreated, it may progress to severe forms such as non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It has also been linked to liver cancer. 57DE7179, 399991Increased risk of gastrointestinal diseaseObesity is associated with: increased risk of gastro-oesophageal reflux and increased risk of gall stones.57DE7179, 399992Increased risk of psychological and social problemsThere are bi-directional associations between mental health problems and obesity, with levels of obesity, gender, age and socioeconomic status being key risk factors. Overweight and obese people can suffer from stress, low self-esteem, social disadvantage, depression and reduced libido.57DE7179