Cancer, Estrogen, and the Metabolic Mess

By George Johnson | November 6, 2013 9:18 pm

If there is a single refrain in the science of cancer that I found most resonant, it is probably this: Anything that causes cells to divide more quickly increases the chance of mutations — random copying errors that arise when the mother cell’s library of genomic information is duplicated, letter by letter, and passed on to its progeny. The right combination of these genetic misspellings can give a cell the power to pursue a life of its own and become the seed of a cancer.

Sometimes the effect is straight forward. Every gulp of alcohol kills cells that line the alimentary tract. That stimulates the growth of new tissue, increasing the rate of cellular division, and raising the risk of esophageal cancer.

A carcinogen, in other words, does not have to be a mutagen — something that alters DNA. Nor does it have to be a foreign substance. One of the functions of estrogen in the female body is to drive the rapid production of new cells in the breasts and uterus. That happens with each turn of the menstrual cycle, these blind preparations for motherhood, leading each month to new mutations and incrementally raising the risk of  cancer. Estrogen is on the National Toxicology Program’s list of 240 human carcinogens, along with ionizing radiation, arsenic, and benzene. (Researchers are investigating whether the hormone also has direct mutagenic effects.)

As I mentioned in my previous dispatch, the indiscriminate use of estrogen supplements to relieve some symptoms of menopause probably created the spike in breast cancer that was recorded in the 1990s. (The effect of estrogen-based contraceptives is far less certain.) But the body’s own natural estrogen can have the same effects. Any list of the risk factors for breast cancer includes delaying or forgoing the bearing of children — for that leads to more lifetime menstrual cycles, each accompanied by a blast of estrogen. The Italian physician Bernardino Ramazzini was first to notice the results. In 1700 he famously reported that nuns seemed to get more breast cancer than other women. (About 150 years later, Domenico Rigoni-Stern discovered another effect of cloistered life: nuns got less cervical cancer, which now is known to be caused primarily by sexually transmitted human papilloma virus.)

Elio Riboli, a cancer epidemiologist I met at Imperial College in London, referred to the phenomenon I’m describing  as “metabolic carcinogenesis” — the body’s ability to give itself cancer. It includes other factors like obesity — fat cells copiously secrete estrogen — and diabetes. All three conditions feed on each other and all three are tied in with insulin regulation.

There are loops within loops, with some surprising variations. Being tall and thin doesn’t necessarily eliminate cancer risks. The stimulating effects of natural growth hormones may be the reason why the Million Women Study found that for every four inches over five feet in height, cancer risk increased by 16 percent.

And here is a mysterious twist that I wrote about in The Cancer Chronicles, involving Ecuadoran villagers with a kind of dwarfism called Laron syndrome:

Because of a mutation involving their growth hormone receptors, the tallest men are four and a half feet and the women are six inches shorter. Life is not easy for them. The children are prone to infections and adults frequently die from alcoholism and fatal accidents. But they hardly ever get cancer or diabetes, even though they are often obese.

I try to untangle the complex hormonal knots in a chapter of the book I called “The Metabolic Mess.” Included is the fascinatingly intricate process of inflammation, which has become  recognized as a powerful trigger of cancer. Inflammation is, after all, a healing mechanism that involves the rapid creation of new tissues — more cellular divisions, more DNA duplication, and more genetic mutations.

A chronic infection of h. pylori bacteria may be a cause of stomach cancer. And inflammation is  another means through which alcohol wields its carcinogenic effects: it can lead to the inflammatory state called cirrhosis of the liver. And that can be a precursor for cancer.

***

Related Posts: The End of Pinktober
The Most Powerful Carcinogen is Entropy

Comments are welcome by email. For public discussion please use Twitter.

For a look at my new book, The Cancer Chronicles, including the table of contents and index, please see this website.

@byGeorgeJohnson

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Whether a subtle new pattern shows up in an experiment on the Higgs boson, an epidemiological report about a suspected cancer cluster, or a double-blind trial purporting to demonstrate ESP, it can be maddeningly difficult to distinguish between what we see and what we think we see. "Fire in the Mind" takes a look at the big questions behind today’s science news.

About George Johnson

George Johnson writes about science for the New York Times, National Geographic Magazine, Slate, and other publications. His nine books include The Cancer Chronicles: Unlocking Medicine's Deepest Mystery (August 2013), The Ten Most Beautiful Experiments, A Shortcut Through Time, and Fire in the Mind. He is a winner of the AAAS Science Journalism Award and has twice been a finalist for the Royal Society science book prize. Co-founder and director of the Santa Fe Science Writing Workshop, he can be found on the Web at talaya.net. Twitter @byGeorgeJohnson.

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