Obesity and cancer

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The association between obesity, as defined by a body mass index of 30 or higher, and risk of a variety of types of cancer has received a considerable amount of attention in recent years. [1] Obesity has been associated with an increased risk of esophageal cancer, pancreatic cancer, colorectal cancer, breast cancer (among postmenopausal women), endometrial cancer, kidney cancer, thyroid cancer, liver cancer and gallbladder cancer. [2] Obesity may also lead to increased cancer-related mortality. [1] Obesity has also been described as the fat tissue disease version of cancer, where common features between the two diseases were suggested for the first time. [3]

Contents

Importance of obesity in causing cancer

The approximate relative levels of the preventable causes of cancer in the United States, taken from the article Cancer prevention Preventable Causes of Cancer in US.png
The approximate relative levels of the preventable causes of cancer in the United States, taken from the article Cancer prevention

About 75-80% of all cancers in the United States are preventable, if risk factors are avoided [4] (also see (Cancer prevention). Obesity appears to be the third most important risk factor for cancer in the United States, just behind tobacco and diet (see Figure). Obesity is the source of about 15% of all preventable cancers. [5] [6] [7]

In 2018, Chinese researchers performed a systematic review and comprehensive quantitative meta‐analysis of cohort studies reporting body mass index (BMI) and the risk of 23 cancer types, providing epidemiological evidence supporting the association between BMI and cancer risk. The strongest positive association between BMI and cancer risk was found among patients in North America. [8]

Mechanisms

The mechanisms by which obesity may increase the risk of cancer are not well understood, [1] but it is believed that the combined effects of the adipose tissue environment and the endocrine alterations that accompany it among obese people both interact to promote tumor initiation and progression. [9] Adipose tissue also creates an inflammatory environment that enhances the ability of tumor cells to metastatize. [10]

The U.S National Cancer Institute indicates that one of the main ways in which obesity can cause cancer is by promoting chronic low-level inflammation, which can, over time, cause DNA damage that leads to cancer. [11] Articles supporting this view were reviewed by Cerda et al. [12] There are also a number of hormonal, metabolic and other changes caused by obesity that may affect carcinogenesis. [11] A review by Tahergorabi et al. summarizes articles indicating that obesity induces changes in angiogenesis, inflammation, interaction of proinflammatory cytokines, endocrine hormones, adipokines including leptin and adiponectin, insulin, growth factors, estrogen, progesterone and cell metabolism. [13]

DNA damage appears to be the primary cause of cancer (see Carcinogenesis). [14] It is not clear which factor(s) altered by obesity are major source(s) of the DNA damages causing increased cancer risk in obese individuals. However, both reduced DNA repair and increased DNA damage are observed in obese individuals.

Reduced DNA repair

As first noted in 2005, [15] there is evidence that overweight/obesity is associated with reduced DNA repair capacity. This was shown, in particular, in women with breast cancer. [16]

Lymphocytes from postmenopausal obese women also have reduced DNA repair capacity compared to non-obese postmenopausal women. [17]

If DNA repair is reduced by obesity, this would allow DNA damages to accumulate. Excess DNA damages, when present in replicating cells, can cause an increase in oncogenic mutations through error-prone translesion synthesis during replication.

Increased DNA damage

An 8-fold and 5.6-fold increase in nuclear damage was observed in lymphocytes of obese and overweight children respectively, compared to children of normal weight, evaluated by the gamma-H2AX focus assay. [18] The gamma-H2AX assay generally reflects the presence of double-strand breaks in DNA, though the assay may indicate other DNA damages as well. [19] Similarly, there was a 2.7-fold and 2.5-fold increase in micronuclei in lymphocytes of obese and overweight children respectively, compared to children of normal weight. [18] Micronuclei are usually a sign of genotoxic events and chromosomal instability (see Micronucleus).

8-dihydro-2'-deoxyguanosine (8-oxodG) concentration in peripheral blood lymphocytes is an index of nuclear DNA damage. 8-oxodG damages are mutagenic. The level of 8-oxodG was measured in 58 overweight and obese adult patients as well as in 20 normal weight individuals. The level of 8-oxodG correlated positively with body mass, BMI, hip circumference and triglyceride concentration. [20]

In a study by Donmez-Altuntas et al., [21] 83 obese, 21 over-weight and 21 normal-weight subjects were tested. Frequencies of DNA damages as measured by frequencies of micronuclei, nucleoplasmic bridges and nuclear buds were found to be significantly higher in lymphocytes of obese subjects than in normal-weight and over-weight subjects (p<0.01 and p<0.05) respectively.

Hofer et al., [22] used the enzyme formamidopyrimidine DNA glycosylase (FPG) and gel electrophoresis to measure levels of DNA damage (oxidized purines). They found two factors that can affect DNA damage in a young healthy population. These were fruit intake (high intake; lower DNA damage) and BMI (high BMI; higher DNA damage).

In the study by Tafurt-Cardona et al., described above, where they found reduced DNA repair in obese postmenopausal women, they also found increased DNA damages, as measured by frequencies of chromosome aberrations, in the obese postmenopausal women. [17]

Association by cancer site

Bladder cancer

Obesity is associated with an increased risk of bladder cancer. [23]

Breast cancer

Obesity has been found to decrease the risk of breast cancer among African and Caucasian women, but increase it among Asian women. [24] Obesity is also associated with decreased survival among women with breast cancer, regardless of whether the cancer is pre- or post-menopausal. [25]

Colorectal cancer

Both general and central obesity are associated with an increased risk of colorectal cancer (CRC). [26] The relative risk among obese people relative to those of normal weight has been reported to be 1.334. [27] An association between increased BMI and risk of colorectal adenoma has been reported, as has a dose–response relationship between BMI and colorectal adenoma risk. [28] [29] Increased BMI also increases all-cause mortality and mortality from CRC specifically among people diagnosed with CRC. [30]

Lung cancer

Obesity has been found to protect against lung cancer, especially among those who smoke or have smoked cigarettes. [31]

Liver cancer

Obesity affects the liver through non-alcoholic fatty liver disease which can cause steatohepatitis which in turn, due to the inflammation caused by the hepatitis, can cause oncogenic changes in hepatocytes. Dietary or genetic obesity induces alterations of the gut microbiota that result in an increased level of deoxycholic acid, a gut bacterial metabolite considered to cause DNA damage leading to liver cancer. [32]

Renal cell cancer

Obesity is a risk factor for renal cell cancer. [33]

Thyroid cancer

Obese people are at a higher risk of thyroid cancer than are their normal weight counterparts. [34]

Related Research Articles

<span class="mw-page-title-main">Body mass index</span> Relative weight based on mass and height

Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms (kg) and height in metres (m).

<span class="mw-page-title-main">Obesity</span> Medical condition in which excess body fat harms health

Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classified as obese when their body mass index (BMI)—a person's weight divided by the square of the person's height—is over 30 kg/m2; the range 25–30 kg/m2 is defined as overweight. Some East Asian countries use lower values to calculate obesity. Obesity is a major cause of disability and is correlated with various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis.

<span class="mw-page-title-main">Colorectal cancer</span> Cancer of the colon or rectum

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, abdominal pain and fatigue. Most colorectal cancers are due to lifestyle factors and genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.

<span class="mw-page-title-main">Bisphosphonate</span> Pharmaceutical drugs for preventing bone loss

Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate groups. They are thus also called diphosphonates.

<span class="mw-page-title-main">Neoplasm</span> Tumor or other abnormal growth of tissue

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.

Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.

<span class="mw-page-title-main">Childhood obesity</span> Obesity in children

Childhood obesity is a condition where excess body fat negatively affects a child's health or well-being. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of obesity in children and its many adverse health effects it is being recognized as a serious public health concern. The term overweight rather than obese is often used when discussing childhood obesity, as it is less stigmatizing, although the term overweight can also refer to a different BMI category. The prevalence of childhood obesity is known to differ by sex and gender.

<span class="mw-page-title-main">Diet and cancer</span> Connections between dietary habits and cancer

Many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence. Obesity and drinking alcohol have been correlated with the incidence and progression of some cancers. Lowering the consumption of sweetened beverages is recommended as a measure to address obesity.

Bariatric surgery is a medical term for surgical procedures used to manage obesity and obesity-related conditions. Long term weight loss with bariatric surgery may be achieved through alteration of gut hormones, physical reduction of stomach size, reduction of nutrient absorption, or a combination of these. Standard of care procedures include Roux en-Y bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch, from which weight loss is largely achieved by altering gut hormone levels responsible for hunger and satiety, leading to a new hormonal weight set point.

<span class="mw-page-title-main">Risk factors for breast cancer</span> Overview article

Risk factors for breast cancer may be divided into preventable and non-preventable. Their study belongs in the field of epidemiology. Breast cancer, like other forms of cancer, can result from multiple environmental and hereditary risk factors. The term environmental, as used by cancer researchers, means any risk factor that is not genetically inherited.

The obesity paradox is the finding in some studies of a lower mortality rate for overweight or obese people within certain subpopulations. The paradox has been observed in people with cardiovascular disease and cancer. Explanations for the paradox range from excess weight being protective to the statistical association being caused by methodological flaws such as confounding, detection bias, reverse causality, or selection bias.

<span class="mw-page-title-main">Overweight</span> Above a weight considered healthy

Being overweight is having more body fat than is optimally healthy. Being overweight is especially common where food supplies are plentiful and lifestyles are sedentary.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis, sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones that occur during menopause.

<span class="mw-page-title-main">Preventable causes of death</span> Causes of death that could have been avoided

Preventable causes of death are causes of death related to risk factors which could have been avoided. The World Health Organization has traditionally classified death according to the primary type of disease or injury. However, causes of death may also be classified in terms of preventable risk factors—such as smoking, unhealthy diet, sexual behavior, and reckless driving—which contribute to a number of different diseases. Such risk factors are usually not recorded directly on death certificates, although they are acknowledged in medical reports.

<span class="mw-page-title-main">Obesity-associated morbidity</span> Medical condition

Obesity is a risk factor for many chronic physical and mental illnesses.

<span class="mw-page-title-main">Infectious causes of cancer</span> Pathogens as a cause of cancer

Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand.

A person's waist-to-height ratio – occasionally written WHtR – or called waist-to-stature ratio (WSR), is defined as their waist circumference divided by their height, both measured in the same units. It is used as a predictor of obesity-related cardiovascular disease. The WHtR is a measure of the distribution of body fat. Higher values of WHtR indicate higher risk of obesity-related cardiovascular diseases; it is correlated with abdominal obesity.

Cancer is caused by genetic changes leading to uncontrolled cell growth and tumor formation. The basic cause of sporadic (non-familial) cancers is DNA damage and genomic instability. A minority of cancers are due to inherited genetic mutations. Most cancers are related to environmental, lifestyle, or behavioral exposures. Cancer is generally not contagious in humans, though it can be caused by oncoviruses and cancer bacteria. The term "environmental", as used by cancer researchers, refers to everything outside the body that interacts with humans. The environment is not limited to the biophysical environment, but also includes lifestyle and behavioral factors.

<span class="mw-page-title-main">Hereditary cancer syndrome</span> Inherited genetic condition that predisposes a person to cancer

A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

<span class="mw-page-title-main">Cancer prevention</span> Taking measures to decrease cancer incidence

Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality. The practice of prevention depends on both individual efforts to improve lifestyle and seek preventive screening, and socioeconomic or public policy related to cancer prevention. Globalized cancer prevention is regarded as a critical objective due to its applicability to large populations, reducing long term effects of cancer by promoting proactive health practices and behaviors, and its perceived cost-effectiveness and viability for all socioeconomic classes.

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