Adipose tissue and cancer (2)
I’ve read roughly two-thirds of the book by now – I like it, pretty much every page contains new stuff which I didn’t know anything about and it’s quite interesting. Some more stuff from the book below, as well as some comments. As always you can click images to view them in a higher resolution.
“Obesity increases the incidence of many cancers, such as breast, prostate, and colon cancer. However, endometrial cancer is the mostly tightly linked with obesity. Estimates suggest that nearly 40 % of cases of endometrial cancer can be attributed to obesity. […] Obese women have a threefold higher risk of developing endometrial cancer than lean women . […] every increase in BMI of 5 kg/m^2 increases a woman’s risk of the developing of endometrial cancer by approximately 60 % (relative risk, 1.59; 95 % confidence interval [CI], 1.50–1.68) . Endometrial cancer in obese women is more likely to have lower risk features such as endometrioid histology and low/intermediate grade. […] An elevated waist-to-hip ratio, reflecting a preferential deposition of adipose in the abdomen, increases the risk of developing endometrial cancer by 220 % . […] Among the population as a whole, obesity increases the risk of death from endometrial cancer. In a study of 900,000 prospectively followed healthy patients, 57,145 individuals died of cancer over 16 years. The relative risk of death from endometrial cancer in this population was 6.25 for women with a BMI >40 and 2.77 with a BMI between 35 and 39 .”
“As a component of adipose tissue in obese individuals, immune cells, and specifically macrophages, secrete a variety of growth, survival, and proangiogenic factors, as well as bioactive molecules that enable tumor growth and contribute to the remodeling of the tumor microenvironment to facilitate metastases. Furthermore, reactive oxygen and nitrogen species released by activated macrophages are mutagenic and accelerate oncogenic mutations that contribute to cancer risk and progression [30,33]. So, not only does inflamed visceral adipose tissue provide an ideal milieu for the growth of metastatic endometrial cancer but proinflammatory factors also secreted by infiltrating adipose immune cells mediate systemic effects on tumor progression at distant sites, including the endometrium.”
“Taken together, current evidence suggests that through a variety of mechanisms, weight loss and physical activity reduce proproliferative signaling and counteract environmental conditions that support the initiation and progression of endometrial cancer.” […as the figure above illustrates, endometrial cancer is far from the only cancer type where behavioral factors play a large role – US.]
“Multiple epidemiologic studies demonstrate that women who use combination estrogen and progesterone oral contraceptives (OCP) decrease their risk of endometrial cancer by 50 % [78–80]. While there is no data to support a decreased efficacy in endometrial cancer protection in obese women, there are studies that suggest that obese women have a slightly decreased contraceptive efficacy compared to thin women .”
“At the cellular level, overweight and obesity are characterized by the increase in number and size of adipocytes. A lean adult has 35 million adipocytes, each containing 0.4–0.6 μg of triglycerides, whereas an extremely obese person has 125 million adipocytes, each containing 0.8–1.2 μg of triglycerides . Traditionally, adipocytes have been viewed solely as energy depots, but after the discovery of leptin in 1994 and extensive research in the field in the last decades, it has been established that the adipose tissue is an active endocrine organ. The adipocyte is a major source of secreted proteins …”
A really important point which has been repeated, explicitly or implicitly, again and again in this book, and which I thought I should emphasize here using ‘non-textbook language’, is that fat cells aren’t just inactive cells that ‘hang around’ doing nothing. They do a lot of stuff while they’re ‘hanging around’. And when you have a lot of them hanging around in the wrong places, many of the things they’re doing are really quite bad for you. As you’ve probably already inferred, the book goes into a lot more detail about mechanisms and how these things work in detail (to the extent that we even know what’s going on in the first place), but if you don’t remember much from the posts about this book this is at least, I think, one of the key points you should try to remember; adipose tissues are active tissues and they – and the secretions derived from them – play a major role in a variety of contexts, including some contexts which are highly relevant to e.g. cancer pathogenesis. There’s still a lot we don’t know because this stuff is complicated; I link to leptin above, which has been intensively studied and is also relatively intensively covered e.g. in chapter 5 of the book, and the wiki link about adipokines mentions a few others – but I should note here that there are more than 50 different types of adipokines that we know of at this point. Different types of cancer start out in different types of tissues and a diverse set of mechanisms are involved in the disease processes, and so it seems likely that different types of adipokines play different roles in different types of cancers. There are still a lot of things which are not clear, but as they put it in the conclusion of chapter 5: “There are strong epidemiological, molecular, and clinical evidences showing associations between adipokines and the incidence and clinical outcome of cancer.” It should be noted that work on this stuff is not limited to work on just ‘human data’ – lab-work using rodents, which is covered in chapter 6 of the book, has added some details and some interesting observations regarding potential mechanisms of action, and such animal models seem to support ‘a causal link’ of some sort between body weight and the development of specific types of cancers in a number of important (…to humans…) cases, including breast cancer and colon cancer. However the precise mechanisms of action are still far from clear, as they note in their conclusion in chapter 6:
“As detailed here, overweight and/or obesity is associated with an elevated risk of several cancers; however, it is clear that a common disease mechanism was not identified. Although the current literature hypothesizes at least three major components such as sex hormones, insulin-related pathologies, and adipokines, these components cannot explain every aspect of clinical features/disease courses. But as models improve both for obesity and various cancers, hopefully it will become easier to identify mechanisms of action for the relationship of body weight and cancer.”
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