Cancer and obesity: an overview

Recent decades have witnessed major changes in lifestyle that have led to steady increases in average body weight in both developed and less developed countries.¹ A person whose weight is above the normal range is referred to as being overweight. This is determined by calculating the body mass index (BMI, defined as weight in kilograms divided by height in metres squared). Overweight is defined as a BMI of 25-29.9, obesity as a BMI > 30 and severe obesity is defined as a BMI > 40. Obesity is more prevalent in high-income countries, such as the US and the UK, than in low-income countries, such as Brazil and China. It is currently estimated that approximately 50% of men and 35% of women in Europe are overweight or obese.¹

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The high prevalence of obesity in developed countries can be explained, in part, by a lifestyle characterised by over-consumption of energy combined with low physical activity.¹ Lifestyle changes due to economic, social and technological advances have resulted in increased automation and computerisation in the workplace and in the home, a reduction in walking and cycling for transport, a decrease in recreational exercise and an increase in sedentary leisure-time occupations.¹

Other influences on the increase in obesity are environmental and include increased marketing and advertising of food products, increased portion sizes and increased accessibility and availability of food.^2,3

Effects of obesity

The morbidity and mortality associated with being overweight or obese have been known to the medical profession for more than 2,000 years.^4-7 This association between BMI and cause-specific mortality was recently reiterated in the Prospective Studies Collaboration analysis where, in the upper BMI range, each 5kg/m² increase in BMI was shown to be associated with a significant increase in mortality from ischaemic heart disease, stroke, diabetes and respiratory disease.⁸ Obesity also has important social, economic and psychological consequences.^9-14

Epidemiological studies are now providing evidence for a link between increased body weight and a higher risk of developing cancer. In recent years there has been an improved understanding of the impact of obesity on the development of a number of cancer types, with current estimates of overweight and obesity causing approximately 20% of all cancer cases.¹⁵

A US prospective cohort study of over 900,000 men and women has claimed that overweight and obesity in the US could account for 14% of all cancer deaths in men and 20% of those in women.¹⁶ It is also estimated that the total health burden of overweight and obesity may now exceed that for cigarette smoking.¹⁷

Obesity and Ireland

Obesity remains a major public health problem in Ireland. A 2011 Irish Nutrition Survey performed by the Irish Universities Nutrition Alliance has revealed that, among 18-64-year-olds in Ireland, a total of 24% are obese (men 26%, women 21%) and 37% are overweight (men 44%, women 31%).¹⁸

Within this age group, the percentage of the population classified as overweight or obese was shown to be increasing with advancing age. In those aged 65 and over, 49% of women and 59% of men are overweight and 24% of women and 25% of men are obese.¹⁸ The prevalence of obesity in 18-64-year-old adults has risen significantly since 1990, from 8% to 26% in men and from 13% to 21% in women, with the greatest increase observed in men aged 51-64 years.¹⁸

Obesity is also a common problem among children, with overweight and obesity now classed the most common childhood disorder in Europe.¹⁹ Over 20% of Irish 5-12-year-olds are now classified as overweight or obese,²⁰ and overweight children tend to become overweight adults.²¹

It has been estimated that ingestion of 5% more calories than expended may result in 5kg of adipose tissue or body fat accumulation in one year.²² The cost of  treating obesity in Ireland has been estimated at €0.4 billion, and approximately 2,000 premature deaths annually in Ireland have been attributed to obesity.²³

Increased cancer rates

Parallel with this increase in obesity, we have witnessed a dramatic increase in the incidence of cancer in Ireland. Overall, cancer incidence in Ireland is high compared to other European countries, with females ranked second and males ranked fourth overall. International comparisons show that mortality rates for Irish men compare quite favourably with our European neighbours, but the incidence and mortality rates for women are among the highest in Europe.²⁴

Oesophageal cancer

Obesity has been strongly implicated in the pathogenesis of oesophageal adenocarcinoma, with overweight and obese men and women reported to be twice as likely as those of a healthy weight to develop oesophageal adenocarcinoma.^25-29 A smaller increased risk has been found for gastric cancer of the cardia.^28‑29 A BMI > 30kg/m² has been shown in a meta-analysis to be associated with a relative risk of 3.0 for developing oesophageal adenocarcinoma.³⁰ This represents a higher association than for any other cancer. Evidence suggests that insulin and the insulin-like growth factor (IGF) axis play an important role in mediating obesity-associated malignancy.³¹ Studies have also highlighted an association between IGF with visceral obesity and a potential impact on the biology of oesophageal adenocarcinoma.³²

Breast cancer

The first evidence that heavier women are at increased risk of breast cancer was obtained in the 1970s. The effect of obesity on breast cancer has been reported to depend on a woman’s menopausal status. Before menopause, obese women have a lower risk of developing breast cancer than do women of a healthy weight.^33-36 After the menopause, obese women have a 1.5 times increased risk of developing breast cancer than women of a healthy weight.^33,34,36,37 Indeed, weight gain during adult life is also consistently associated with increased risk of postmenopausal breast cancer.^38-42

The increased risk of developing breast cancer in obese women is believed to be due to increased levels of oestrogen.⁴³ It is also reported that breast cancer is more likely to be detected at a later stage in obese versus lean women and that overweight and obese women are less likely to be screened for breast cancer with mammograms.^35,44

Colorectal cancer

Colon cancer has also been shown to occur more frequently in people who are obese than in those of a healthy weight.^25,45‑49 The risk of colon cancer increases by 25% in overweight men and by approximately 50% in obese men.^46,49-51 The relationship between BMI and colon cancer risk in women, however, has been found to be weaker or absent.^46,50,52 Studies have reported a stronger association for colon than for rectal cancer and the distal colon appears more affected than the proximal colon.^1,46,53,54

Endometrial cancer

Obese women have two to four times greater risk of developing endometrial cancer than women of a healthy weight, regardless of menopausal status, and this risk increases linearly with increases in BMI above 25.^1,25,55-58

Renal cell cancer

Studies have consistently found a link between renal cell carcinoma and obesity in women, with some studies reporting the risk among obese women to be two to four times the risk of women of a healthy weight.^25,59-62 Results of studies involving men have been more variable, ranging from an association similar to that seen in women, to a weak association, to no association at all.^59,60,62

Pancreatic cancer

Two large prospective studies in the US support a link between obesity and pancreatic cancer and a meta-analysis has shown a 19% risk increase of pancreatic cancer for obese individuals.^63-66

Other cancer types

An increased risk of gallbladder cancer has been found to be associated with obesity, especially among women.^67-69 This may be due to the higher frequency of gallstones in obese individuals, which are considered a strong risk factor for gallbladder cancer.^67‑69 Some studies report an increased risk of ovarian cancer among obese women, whereas others have found no association.^70-74 Most studies on prostate cancer conclude that there is no association between prostate cancer and obesity.^1,25,75-77

Studies evaluating the relationship between hepatic cancer and obesity have been inconsistent, with some studies reporting a link and others not.^78,79 Lung cancer risk is shown to be inversely associated with BMI, but this association seems to be confounded by cigarette smoking history.²⁵ Data are scarce on the relationship between haematopoietic cancers and BMI, and the findings have not been consistent.¹⁶

Mechanism of altered cancer risk

The mechanisms by which weight, diet and physical activity influence tumour formation and progression are not completely understood. As the pathophysiology of obesity is complex and multisystemic, it is unlikely that ‘one size fits all’. A number of putative processes have therefore been proposed.¹⁵ The mechanisms underlying the effect of obesity and weight change vary by tumour site. In part, these associations with cancer risk may be explained by alterations in the metabolism of endogenous hormones, including sex steroids, insulin, and insulin-like growth factors, which can lead to distortion of the normal balance between cell proliferation, differentiation and apoptosis.¹ Female hormones would appear to be implicated in breast and endometrial cancer, but have much less impact on other cancers. Insulin may be the drive behind colon cancer and inflammation is thought to drive other malignancies.¹⁵

Effect of obesity on survival

For both men and women increasing BMI has been shown to be associated with higher death rates from a variety of cancers, including oesophageal cancer, colorectal cancer, pancreatic cancer and renal cell cancer.¹⁶

Obese women have been shown to be at increased risk of dying from cervical cancer, ovarian, endometrial and postmenopausal breast cancer compared with lean women.^{16,25,33-35,80,81} Obese men are also at increased risk of death from stomach cancer.¹⁶ Although prostate cancer is not associated with obesity there is emerging evidence that higher risk of death from prostate cancer has been shown in obese men.⁸²

Weight control and physical activity

A recent review of the current evidence pertaining to dietary factors and cancer incidence and progression, has concluded that despite epidemiological evidence suggesting a link between dietary factors and cancer development, confounding evidence such as obesity, physical activity and the sheer variety of bio-active compounds in a normal diet, pose a great challenge to the study of mechanisms linking diet and cancer.⁸³

While cancer incidence is clearly increased in obese individuals, it is unclear whether weight loss decreases cancer incidence. Nonetheless, avoidance of weight gain should become one of the mainstays of chronic disease prevention in modern societies. 

Studies have shown that many adults are not aware of the link between obesity and cancer.⁸⁴ A Canadian study has reported that only 31% of Canadians thought that being overweight was a risk factor for cancer and only 28% thought that lack of exercise was linked to cancer. In contrast, the majority of Canadians (83% and 78%) associated overweight with heart disease and diabetes, respectively.⁸⁴

The best way to achieve a healthy body weight is by balancing energy expenditure with energy intake. Excess weight can be reduced through increasing physical activity and by restricting calorific intake. The association between physical activity and decreased risk for breast cancer and colon cancer has been demonstrated across levels of obesity.^85-87 Limited evidence suggests that increased physical activity offers some protection against endometrial and prostate cancer.^15,47,88,89

Several mechanisms have been proposed to explain the possible effect of physical activity, including: ^90-92

• Reduction in circulating levels of insulin, hormones and other growth factors
• Impact on prostaglandin levels
• Improved immune function
• Altered bile metabolism. 

Only a limited number of studies have addressed this issue and the results are difficult to interpret due to a lack of, or insufficient, information on the cause of the weight loss.¹ Thus, the optimal duration, intensity and frequency of physical activity that may afford cancer protection is unknown.

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Conclusion and future directions

Obesity remains a major public health problem on a national as well as on an international basis. Overweight and obesity are the most important known avoidable causes of cancer after tobacco smoking. The burden of obesity on society continues to increase and warrants closer attention by clinicians. It is estimated that 90,000 cancer deaths could be prevented each year in the US if men and women could maintain normal weight.¹⁶

A better understanding of the mechanisms that link obesity to cancer may help in the development of targets for intervention. Drugs currently under development that inhibit IGF-1 receptor function may prove useful targeted therapies for certain cancers, including adenocarcinoma of the oesophagus, which express IGF-1 receptor.³²

The problem of childhood obesity must be viewed on a global level. The World Health Organization has taken a strong stance on the prevention of obesity, underscoring its global health threat.⁹³

The challenge for providers is to engage the patient in understanding the importance of weight control and increased physical activity. Concerted effort and substantial investment on the part of policy makers, educators and clinicians must be employed in order to achieve this important goal.

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