The association between

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

, as defined by a

body mass index 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 and he ...

of 30 or higher, and risk of a variety of types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

has received a considerable amount of attention in recent years. Obesity has been associated with an increased risk of

esophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice ...

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

(among postmenopausal women),

endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...

kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spr ...

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...

and

gallbladder cancer Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States. It is particularly common in central and South America, central and eastern Europe, Japan and northern Ind ...

. Obesity may also lead to increased cancer-related mortality. 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.

Importance of obesity in causing cancer

About 75-80% of all cancers in the United States are preventable, if risk factors are avoided (also see (

Cancer prevention Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality. The practice of prevention is dependent upon both individual efforts to improve lifestyle and seek preventive screening, and socioeconomi ...

). 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. In 2018, Chinese researchers performed a systematic review and comprehensive quantitative meta‐analysis of cohort studies reporting

(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.

Mechanisms

The mechanisms by which obesity may increase the risk of cancer are not well understood, 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. Adipose tissue also creates an inflammatory environment that enhances the ability of tumor cells to metastatize. 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. Articles supporting this view were reviewed by Cerda et al. There are also a number of hormonal, metabolic and other changes caused by obesity that may affect carcinogenesis. 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. DNA damage appears to be the primary cause of cancer (see

Carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

). 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, there is evidence that overweight/obesity is associated with reduced DNA repair capacity. This was shown, in particular, in women with breast cancer. Lymphocytes from postmenopausal obese women also have reduced DNA repair capacity compared to non-obese postmenopausal women. 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 DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

during replication.

Increased DNA damage

An 8-fold and 5.6-fold increase in nuclear damage was observed in

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s of obese and overweight children respectively, compared to children of normal weight, evaluated by the gamma-H2AX focus assay. The gamma-H2AX assay generally reflects the presence of double-strand breaks in DNA, though the assay may indicate other DNA damages as well. 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. Micronuclei are usually a sign of genotoxic events and chromosomal instability (see

Micronucleus Micronucleus is the name given to the small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal i ...

). 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. In a study by Donmez-Altuntas et al., 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., used the enzyme

formamidopyrimidine DNA glycosylase DNA-formamidopyrimidine glycosylase (, ''Fapy-DNA glycosylase'', ''deoxyribonucleate glycosidase'', ''2,6-diamino-4-hydroxy-5N-formamidopyrimidine-DNA glycosylase'', ''2,6-diamino-4-hydroxy-5(N-methyl)formamidopyrimidine-DNA glycosylase'', ''formam ...

(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.

Association by cancer site

Bladder cancer

Obesity is associated with an increased risk of

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...

Breast cancer

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

Colorectal cancer

Both general and

central obesity Abdominal obesity, also known as central obesity and truncal obesity, is a condition when excessive visceral fat around the stomach and abdomen has built up to the extent that it is likely to have a negative impact on health. Abdominal obesity has ...

are associated with an increased risk of

(CRC). The

relative risk The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...

among obese people relative to those of normal weight has been reported to be 1.334. An association between increased BMI and risk of colorectal adenoma has been reported, as has a

dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. ...

between BMI and colorectal adenoma risk. Increased BMI also increases all-cause mortality and mortality from CRC specifically among people diagnosed with CRC.

Lung cancer

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

Liver cancer

Obesity affects the liver through

non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...

which can cause

steatohepatitis Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes. T ...

which in turn, due to the inflammation caused by the hepatitis, can cause oncogenic changes in hepatocytes.

Renal cell cancer

Obesity is a risk factor for

renal cell cancer Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, resp ...

Thyroid cancer

Obese people are at a higher risk of

than are their normal weight counterparts.

References

{{Reflist Medical conditions related to obesity Cancer