Overweight and obesity, generally assessed by various anthropometric measures including body mass index (BMI) and waist circumference, are now more prevalent than ever.
Approximately 2 billion adults are living with overweight and obesity and, within this group, 800 million are living with obesity (defined as a BMI =>30).
being overweight or living with obesity throughout adulthood INCREASES the risk of
being overweight or obese between the ages of about 18 and 30 years DECREASES the risk of
The evidence also shows that, in general, the more weight people gain as adults, the higher the risk of postmenopausal breast cancer. In contrast, the evidence shows that, in general, the more excess weight people have as young adults, the lower the risk of breast cancer. Despite this finding, we recommend maintaining a healthy weight throughout all stages of life.
There’s also other evidence on being overweight or obese throughout adulthood that is limited (either in amount or by methodological flaws), but is suggestive of an increased risk of cervical cancer for women with a BMI of 29 kg/m2 or more. Further research is required, and we haven’t used this evidence to make recommendations.
The increase in the proportion of adults categorised as living with obesity has been observed both in low- and middle-income countries and in high-income countries. Although the rate of increase has begun to slow in some high-income countries, the prevalence of obesity has tended to accelerate in low- and middle-income countries.
These accelerations have occurred in tandem with considerable changes in food systems and dietary patterns, commonly termed the ‘nutrition transition’. Overweight and obesity is occurring at an ever earlier age, increasing lifetime exposure to the associated risks.
Excess weight and obesity have been linked to a number of other chronic diseases including cardiovascular disease, diabetes and other metabolic disorders.
Excess energy from food and drink is stored in the body as fat in adipose tissue. The amount of adipose tissue in the body varies more from person to person than any other type of tissue (such as muscle, bone or blood).
The size and location of these fat stores also vary considerably between populations, between people and over the course of a person’s life. Excess body fat is a cause of a number of chronic diseases and reduces life expectancy.
Of course, excess weight gain is not itself a behaviour, rather the result of many different behaviours. To build on our findings about how weight influences cancer risk, the Third Expert Report included a review of factors influencing excess weight gain.
Balancing energy intake and expenditure
Maintenance of stable body weight in adulthood depends on the close matching of energy intake (through food and drink) and energy expenditure (through the body’s basic functions and physical activity) over the long term, called energy balance. Under normal circumstances energy balance is achieved through interaction between the body’s regulatory systems, including appetite, together with an important role for learning, memory and physical activity. These interactions can be influenced by a variety of factors, both internal (for example, genetic variation) and external (for example, changes in the composition of food and drink and the social circumstances in which they are consumed).
In addition to the findings in the Third Expert Report related to diet, nutrition and physical activity, other established influences on energy balance and body weight include:
Identical twin studies have identified many genetic variants that contribute to weight gain, principally by influencing appetite. However, mutations and chromosomal rearrangements known to cause obesity, such as congenital leptin deficiency, Prader-Willi Syndrome and Bardet-Biedl syndrome, are rare.
- epigenetics and maternal programming
The womb environment is an important determinant of fetal phenotype and disease risk in later life. Factors such as nutrition or infection influence the pattern of fetal gene expression and risk of weight gain, overweight and obesity. Infants of mothers who are obese tend to have greater fetal size and increased fat mass – both risk factors for obesity.
There is early but growing evidence that the bacteria residing in the colon – the microbiome – may be involved with the development of overweight and obesity, although the mechanisms are not fully established.
Psychosocial factors that can influence body weight, including risk of overweight or obesity, include stress, discrimination, depressive mood and emotional eating disorders.
- environmental and policy factors
Overweight and obesity are complex issues, influenced by many factors outside of people’s direct personal control. Broadly, these are economic, social and environmental factors that operate at global, national and local levels. At a personal level these are experienced as the availability, affordability, awareness and acceptability of healthy diets and physical activity, relative to unhealthy diets and physical inactivity.
Adult body fatness and oesophageal cancer (adenocarcinoma)
Increased body fatness may promote chronic gastroesophageal reflux disease or inflammation of the oesophagus; this may lead to the development of Barrett’s oesophagus which has been shown to increase the risk of developing oesophageal adenocarcinoma. Further research is needed to better understand the biological mechanisms that underlie the association of body fatness with oesophageal adenocarcinoma.
Adult body fatness and pancreatic cancer
Body fatness may influence the development of pancreatic cancer through similar and diverse mechanisms purported to underlie its cancer-promotive role at other anatomical sites.
Elevated chronic inflammation with activation of NF-kappaB signaling, increased production of proinflammatory cytokines and pancreatic infiltration of immunosuppressive cells have all been proposed as possible mechanisms. In addition, higher body fatness has been associated with increased levels of hormones such as insulin, which can promote cell growth and inhibit apoptosis, and hence could be cancer promotive.
A recent Mendelian randomisation analysis performed in a study of more than 7,000 pancreatic cancer cases and 7,000 controls found robust evidence for a strong association between genetic variants that determine higher body fatness and circulating insulin levels and pancreatic cancer risk, suggesting a causal role for body fatness in pancreatic cancer development.
Adult body fatness and liver cancer
Although the exact mechanisms linking obesity and liver cancer development are still unclear, recent evidence supports a role for greater body fatness in the development of non-alcoholic fatty liver disease (NAFLD), which is strongly linked to metabolic syndrome and which can lead to a complex dysregulation of hepatic lipid metabolism.
In its more aggressive forms, NAFLD can drive inflammation and hepatic tissue damage by increasing endoplasmic reticulum stress, elevating production of reactive oxygen species (increased oxidative stress), and higher inflammation.
Body fatness is associated with host chronic inflammation and insulin resistance and may contribute to the hepatic dysfunction underlying this relationship. Obesity is associated with increased levels of pro-inflammatory cytokines (for example TNF-alpha and IL-6) and insulin, which can promote hepatocyte growth and malignant transformation through activation of the oncogenic transcription factor Signal Transducer and Activator of Transcription-3.
The resulting chronic liver injury due to chronic inflammatory processes can promote compensatory hepatocyte injury, death, tissue remodeling and regeneration, which has been shown in animal models to be a necessary factor for liver cancer development. Animal studies also suggest that gut bacterial dysbiosis within the context of NAFLD may also propagate liver injury.
Adult body fatness and colorectal cancer
Higher body fatness is associated with changes in hormonal profiles, such as increased levels of insulin, which can promote the growth of colon cancer cells and inhibit apoptosis. Higher serum concentrations of insulin and IGF-1 have been linked to greater risk of colorectal cancer in human and experimental studies.
Body fatness also stimulates the body’s inflammatory response, which can promote development of colorectal cancer. Overall, there are convincing mechanistic data supporting a link between body fatness and colorectal cancer.
Adult body fatness and post-menopausal cancer
Body fatness directly affects levels of several circulating hormones, such as insulin and oestrogens, creating an environment that promotes carcinogenesis and suppresses apoptosis.
In postmenopausal women, when the production of oestrogens from the ovaries has dramatically declined, the main source of oestrogens is from the conversion of androgens within the adipose tissue. Consequently, overweight and obese women have higher circulating levels of oestrogens, which are well known to be associated with the development of breast cancer.
Other sex steroid hormones, including androgens and progesterone, are also likely to play a role in the relationship between obesity and breast cancer. Elevated body fatness is also associated with hyperinsulinemia and insulin resistance, and greater circulating insulin levels have been linked to breast cancer risk.
Insulin could promote breast tumour growth directly by binding to its receptor or to the IGF-I (insulin-like growth factor-I) receptor or indirectly by inhibiting the synthesis of sex-hormone binding globulin, which sequesters oestrogens in circulation, contributing to higher levels of bioavailable oestrogens.
Obesity is also associated with a low-grade chronic inflammatory state. Adipose tissue in obese individuals secretes pro-inflammatory cytokines and adipokines, which can promote development of breast cancer, as shown in experimental studies and more recently in epidemiological studies.
Adult body fatness and endometrial cancer
Excess body fatness increases bioavailable oestrogen levels that have been shown, when not counterbalanced by progesterone, to increase endometrial tissue mitotic activity and therefore promote endometrial carcinogenesis. Higher insulin levels associated with excess body fatness are associated with greater risk of endometrial cancer.
Insulin has been shown to enhance endometrial tumour growth either directly by binding to the insulin or to the IGF-I receptors or indirectly by inhibiting the synthesis of sex hormone binding globulin and thereby increasing oestrogen bioavailability. Obesity-related chronic inflammation has also been specifically linked to development of endometrial cancer.
Adult body fatness and kidney cancer
The vast array of epidemiological studies using diverse measures of obesity, such as weight, BMI or waist-hip ratio as well as increases in adult weight, all show similar positive associations with the risk of renal cell cancer and likely share common mechanisms.
Body fatness is a systemic process affecting host metabolism, as well as many components of the endocrine system or microenvironment, that may affect kidney carcinogenesis. For example, obesity is associated with raised levels of mitogenic and anti-apoptotic growth factors such as insulin or bioactive IGF-1 that may promote the carcinogenic process.
Higher concentrations of adiponectin, a protein secreted by adipose tissue that is inversely related to body fatness, have been associated with lower risk of kidney cancer. In vitro experimental studies have shown that adiponectin inhibits cellular proliferation and promotes apoptosis.
Obesity increases the risk of metabolic syndrome, which includes hypertension and obesity, both of which are associated with a greater risk for renal cancer. Obesity is associated with a chronic inflammatory state that may alter susceptibility to cancer or promote carcinogenesis.
Adult body fatness and cancers of the mouth, pharynx and larynx
Specific mechanisms to support the relationship between body fatness and mouth, pharynx and larynx cancers have not been proposed to date. However, greater body fatness is associated with metabolic and endocrine abnormalities such as hyperinsulinemia and elevated levels of bioavailable oestrogen, and in other tissues, insulin and oestrogen have been shown to stimulate mitogenesis and inhibit apoptosis, leading to enhanced cellular proliferation.
Obesity has also been shown to stimulate the inflammatory response, which may also promote tumorigenesis. Further research on the mechanisms underlying the link between obesity and cancers of the mouth, pharynx and larynx is needed.
Adult body fatness and cancers of the mouth, pharynx and larynx
Specific mechanisms to support the relationship between body fatness and mouth, pharynx and larynx cancers have not been proposed to date. However, greater body fatness is associated with metabolic and endocrine abnormalities such as hyperinsulinemia and elevated levels of bioavailable oestrogen, and in other tissues, insulin and oestrogen have been shown to stimulate mitogenesis and inhibit apoptosis, leading to enhanced cellular proliferation.
Obesity has also been shown to stimulate the inflammatory response, which may also promote tumorigenesis. Further research on the mechanisms underlying the link between obesity and cancers of the mouth, pharynx and larynx is needed.
Adult body fatness and stomach cancer (cardia)
Greater body fat promotes the development of chronic gastroesophageal reflux disease or inflammation of the oesophagus, the potential transition to Barrett’s oesophagus, and increases the risk of developing cardia stomach cancer. Being overweight and obese is also associated with higher levels of insulin, which can act as a mitogen and has anti-apoptotic properties and therefore may represent a mechanism, though there are limited data to support this hypothesis to date. Obesity has also been shown to stimulate the inflammatory response, which may promote tumorigenesis.
Adult body fatness and gallbladder cancer
The mechanisms underlying the positive association of body fatness with gallbladder cancer development are likely to be similar to those proposed for other anatomical sites, namely development of metabolic syndrome and its components, such as hyperglycemia, dyslipidemia, hyperinsulinemia and hypertension. Chronic inflammation, production of growth factors and increased levels of pro-inflammatory cytokines are also possible cancer-promoting consequences of increased body fatness.
Interestingly, body fatness and metabolic syndrome appear to be associated with increased risk of gallstones, which has been observed as a major risk factor for gallbladder cancer development in various populations, likely through promotion of increased chronic inflammation at this site. The stronger association of body fatness with gallbladder cancer in women than in men may in part be due to adverse effects of female sex hormones on hepatic bile secretion and gallbladder function.
Adult body fatness and ovarian cancer
Greater body fatness is associated with higher circulating levels of endogenous oestrogens and androgens, and these hormones are associated, albeit inconsistently, with higher risk of ovarian cancer. Adipose tissue is also a source of adipokines and inflammatory cytokines that promote a low-grade inflammatory milieu, and both local and systemic pro-inflammatory factors are associated with development of ovarian cancer.
Adult body fatness and advanced prostate cancer
Greater body fatness is associated with higher risk of advanced prostate cancer. Several biological mechanisms have been proposed that link adiposity to cancer, including dysregulated sex steroid metabolism, hyperinsulinemia and elevated levels of proinflammatory cytokines; however, the evidence linking these pathways specifically to prostate cancer is limited.
Androgens such as testosterone play critical roles in the development and function of the prostate gland. It has been hypothesised that a hypoandrogenic environment promotes the development of higher-grade prostate tumours, and at least two prospective studies have reported inverse relationships between serum testosterone levels and higher-grade prostate cancer.
Testosterone levels tend to be lower in obese males than in those of normal weight and therefore may represent a potential mediator of the body fatness-advanced prostate cancer relationship. Hyperinsulinemia has been shown to accelerate tumour growth in prostate cancer xenograft models, and human prostate tumours commonly express the insulin receptor, suggesting that insulin may stimulate prostate cancer growth.
However, data in human studies generally do not support a relationship between hyperinsulinemia and prostate cancer development. Similarly, proinflammatory cytokines and adipokines such as leptin have been shown to exert a mitogenic effect in prostate cancer cell lines that are human androgen-independent, inducing proliferation and inhibiting apoptosis, while epidemiologic data generally do not support an association between inflammatory cytokines and development of prostate cancer.
Overall, further research is needed to advance knowledge on the mechanisms that potentially underlie the association of body fatness with advanced prostate cancer.
Adult body fatness and cervical cancer (BMI ≥ 29)
Specific biological mechanisms underlying the association between body fatness and cervical cancer are not well understood, but may be similar to the mechanisms proposed for other cancers.
Experimental models of cervical cancer are poorly developed, and few have been employed in studies of diet and nutrition. A major cause of cervical cancer is infection by human papilloma virus (HPV), and it is plausible that certain hormonal and metabolic changes that are common in obesity could act as co-factors in HPV-related carcinogenesis.
For example, higher circulating oestrogen and androgen levels are common in obese women and in mouse models of HPV-induced cervical cancer, and oestradiol has been shown to synergise with HPV oncogenes to promote the development of cervical cancer. However, this would not represent a plausible mechanism in younger women (in whom the majority of cervical cancers occur) as obese premenopausal women do not generally have raised oestrogen levels.
Other possible biological mechanisms include obesity-induced changes in immune function that could affect clearance of HPV infection and elevated levels of inflammation; however, direct evidence for a link between these pathways and cervical cancer is only beginning to be examined.
Adult body fatness and premenopausal breast cancer
There is no single well-established mechanism through which body fatness could prevent premenopausal breast cancer. One possible mechanism relates to anovulation, which is commonly associated with obesity and results in abnormal hormone profiles characterised by lower endogenous levels of progesterone.
Although the mechanisms of the potential protective effect of obesity on premenopausal breast cancer have not been fully elucidated, it appears to be related to fat distribution, as a higher waist circumference seems to be more strongly associated with an increased risk of premenopausal breast cancer after accounting for BMI.
Mechanisms specifically related to abdominal adiposity measured by waist circumference include a strong relationship to chronic inflammation and insulin resistance.
Body fatness in young adulthood
Body fatness in childhood and adolescence is inversely related to the risk of premenopausal breast cancer as well as postmenopausal breast cancer, suggesting a long-term effect of body fatness at young age on breast cancer risk later in life.
These findings contrast with the higher risk of breast cancer among postmenopausal women who have greater body fatness in adulthood. Early life, including childhood and adolescence, is hypothesised to be a critical window for breast carcinogenesis. This is a period of rapid growth and development of breast tissue, with higher rates of mammary gland tissue proliferation during puberty, which may increase susceptibility to molecular damage and may explain why particular exposures may be important for breast cancer risk later in life.
Body fatness during childhood has been associated with slower adolescent growth and development; however, peak height growth velocity as a measure of adolescent development is associated with an increased risk of breast cancer. Higher circulating levels of IGF-I, the main mediator of growth hormone activity, is an established positive risk factor for breast cancer but may be lower among women who had greater body fatness in childhood and adolescence.
Sex hormones may also partly explain the inverse relation between adiposity in early life and risk of breast cancer. Adipose-tissue-derived oestrogen in overweight adolescents may induce early breast differentiation and render the breast tissue less susceptible to carcinogenesis, as has been demonstrated in animal models.
Obese young women are also more likely to experience anovulation and therefore lower levels of ovarian hormones such as progesterone and lower peaking of oestradiol. However, body fatness in pre-adolescent and adolescent girls is related to higher insulin and androgen levels and lower sex hormone binding globulin concentrations, which would be hypothesised to increase breast cancer risk.
Overall, the mechanisms underlying the inverse association of early life body fatness and breast cancer risk are complex, likely multiple and not well-delineated.
In 2018, we produced the Diet and Cancer Report, the third in our series of major reports looking at the many ways in which our diets, and how active we are, affect our cancer risk. You can find out much more about weight gain and the risk of cancer by downloading a pdf of the relevant chapter in the 2018 report. Please note, however, that this webpage may have been updated since the report was published.
