Why obesity increases the risk of cancer

Why obesity increases the risk of cancer

A recent study shows that metabolic disturbances caused by obesity interfere with the elimination of cancer cells by the immune system and promote cancer development.

The steady increase in the number of overweight people observed in recent years has several negative repercussions on human health all over the world.

In addition to being an important risk factor for several serious pathologies (type 2 diabetes, atherosclerosis, hepatic steatosis) which considerably reduce life expectancy, we now know that obesity is also a major cause of death associated with a host of other diseases, whether it be autoimmune diseases, certain infectious diseases (including COVID-19) or cancer.

In the latter case, it is now established that obesity is a risk factor for at least 13 different types of cancer and that the incidence of these cancers has increased significantly in recent years, including in young adults, and these cancers represent around 40% of new cancer cases diagnosed annually (1).

With the constant increase in the number of overweight people, we can therefore predict that this negative impact of obesity will continue to grow over the next few years and may even overtake tobacco as the main cause of cancer.

Tumor microenvironment

The increased risk of cancer from being overweight is caused by the many metabolic disturbances caused by excess fat (dyslipidemia, insulin resistance, chronic inflammation) which collectively create an environment conducive to the progression of cancer cells. .

A clinical study recently published in the very prestigious Cell suggests the existence of a new metabolic upheaval caused by obesity, which favors the development of cancer: the inactivation of killer T cells specialized in the elimination of cancer cells (2).

Researchers have observed that in the presence of excess fat, cancer cells reprogram their metabolism to preferentially use fatty acids instead of sugar as an energy source.

This adaptation causes cancer cells, which proliferate very quickly, to deplete the fat reserves present in the tumor microenvironment and deprive the normal cells there of an ingredient essential for their functions.

This is particularly the case with immune cells specializing in eliminating cancer cells: under normal conditions, these cells (CD8 + killer T lymphocytes) infiltrate tumors to attack cancer cells and prevent cancer development.

Researchers have observed that the decrease in fatty acids caused by gluttony in cancer cells causes an energy deficiency for CD8 + cells which reduces their anticancer activity and allows tumors to grow faster.

These results obtained with animal models are confirmed in humans. For example, analysis of tumor samples from obese patients shows a marked reduction in CD8 + lymphocytes in proximity to cancer cells.

Obesity therefore has an immunosuppressive effect which deprives the body of its main first line defense against the development of cancer and which thereby contributes to the increased incidence of cancer in obese people. Another concrete example of the catastrophic health consequences caused by obesity.

♦ (1) Steele CB et al. Vital Signs: Trends in incidence of cancers associated with overweight and obesity – United States, 2005–2014. MMWR Morb. Mortal. Wkly Rep. 2017; 66: 1052–1058.

♦ (2) Ringel AE et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 2020; 183: 1848-1866.e26.

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