Thursday, January 15, 2015

2-7 Offsuit: Is Cancer Just "Bad Luck"?

There are many forms of cancer that ravage the body, but the key feature they share is uncontrolled cell growth. Virtually any cell type can suddenly go rogue and start reproducing itself again and again – this is what we call a tumor. Some of these rogue cells venture to other parts of the body where they don’t belong and establish a new colony there – this is called metastasis. As cancerous tumors grow and spread around, they can do a number of things that endanger the life of the patient, such as interfere with organ function and steal nutrients from other cells or tissues.

This cartoon illustrates a general model for the development of cancer. A "benign" tumor is not considered cancerous because they do not invade other parts of the body. In contrast, "malignant" tumors, like that ugly looking thing above, are cancerous because they invade nearby tissues. If cells from a malignant tumor get into the bloodstream, they can establish life-threatening satellite tumors elsewhere in the body, making them all the more challenging to eliminate.

Cancer is caused by a change, or mutation, in one of our cell’s DNA. Our DNA contains tens of thousands of genes that encode proteins that make our cells tick. Some of these proteins regulate cell division, but they are normally shut off after the job is done. A mutation that turns one (or more) of these regulatory proteins back on can turn that cell into a Xerox machine stuck on "copy". Since there are so many different types of genes that can mutate in a wide variety of cell types, a “one size fits all” cure is very difficult to conceive.

Scientists (and many pseudoscientists) have long been trying to identify things in our environment that cause mutations that lead to cancer. Others have argued that cancer is just “bad luck” and that our genes play a larger role. This is important to sort out:  should we invest more money to identify potential carcinogens in the environment or to find ways to repair “bad” genes?

Every now and then, someone gets lung cancer who never took a single puff on a cigarette. Why? To understand the answer, consider poker. You can study dozens of books on how to play to win, practice for 10,000 hours, pay hundreds of dollars to learn all the secrets from the professional players. But none of this will help you if the dealer gives you junk cards. To look at this another way, there are some people who start chain smoking at twelve and live to be 90 with no trace of cancer (perhaps breathing through a tube in their throat, but no cancer). That’s like a rookie at the poker table being dealt a straight flush. Long story short:  cancer is not always the patient’s fault, and a lack of cancer is not always indicative of a healthy lifestyle.

In Texas Hold’em poker, you begin with just two cards. Being dealt a 2 and 7, offsuit, is considered the worst possible hand you can get. In contrast, being dealt two aces is one of the best starting hands. The genes that combined to form your DNA are analogous to the cards you would be dealt at a poker table. Unlike the poker game, though, you can’t win by bluffing.

Researchers have found plenty of environmental agents that can mutate DNA. For example, exposure to UV radiation is one of the more notorious risk factors for skin cancer. But there are a few people who worship the sun and never get skin cancer. In addition, most children have not had extensive exposure to environmental carcinogens, yet, tragically, they can still get cancer. In 2014, it was estimated that 15,780 children and adolescents ages 0 to 19 years would be diagnosed with cancer and nearly 2,000 would not survive. Facts such as these support the notion that cancer is largely due to bad genes, not necessarily the environment.

Scientists at Johns Hopkins recently set out to tackle the question by constructing mathematical models of the disease. Their findings might take you by surprise:  in the majority of cases, the reason why a cell starts running all the red lights is due to a random mutation that occurs during cell division. In other words, lifestyle choices and even your genetic makeup play a lesser role in your chances in getting cancer. Let that sink in for a moment: RANDOM mutation - not mutation caused by UV light, engine exhaust, or some other carcinogen. Since the mutation appears to be a random mistake made by cell division enzymes, the authors dubbed this "bad luck".

DNA replication is a complex process in which the two strands are separated and used as a template to make a complementary second strand. But replication enzymes are not perfect (if they were, there'd be no evolution) and sometimes insert the wrong DNA base, causing a mutation.
This new study reminds us that every cell division contains an inherent risk that the daughter cell acquires a mutation that makes it divide like gangbusters. This doesn’t mean you should grab a carton of Marlboros to smoke as you suntan on the beach while devouring a couple extra-charred burgers for lunch.

Highlighted in this study was the finding that not all cell types give rise to cancer equally. Not surprisingly, tissues with a higher number of stem cell divisions are more prone to cancer, which explains why we don’t hear a lot about duodenum cancer. Importantly, the researchers identified several types of cancer that are influenced more by our lifestyle choices or inherited mutations: colon cancer, basal cell carcinoma, and lung cancer.

The findings essentially assert that since cells divide they are veritable time bombs. Somewhere down the line a mistake is going to happen regardless of environmental insults, and if that mistake occurs in the wrong gene, cancer can ensue. These are noncontroversial statements and not news to most people. However, the idea that "most" cancers are due to "bad luck" is a more controversial conclusion. A major limitation is that the model did not incorporate some of the most common cancers, such as breast and prostate cancer, because the frequency of stem cell divisions is unclear. Readers would be wise to check out this article by David Gorski at Science-Based Medicine, which provides detailed insight into the strengths and weaknesses of the experimental design. The World Health Organization was so opposed to the message this study sends that they issued a press release critical of the study.

Obi-Wan (Ben) Kenobi famously said, “In my experience, there’s no such thing as luck.” Some scientists who take issue with the Hopkins study would agree with Ben. 
At the end of the day, since we don’t yet know how all genes operate, much less which ones you might have in your DNA, it is wise to take common sense steps to minimize your exposure to known carcinogens and take advantage of tests designed to detect cancer at its earliest stage. Bad luck may be a major factor in cancer, but there are plenty of simple lifestyle changes you can make to try and beat the odds.

Contributed by: Bill Sullivan
Follow Bill on Twitter.

Tomasetti, C., & Vogelstein, B. (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions Science, 347 (6217), 78-81 DOI: 10.1126/science.1260825

Ward E, DeSantis C, Robbins A, Kohler B, & Jemal A (2014). Childhood and adolescent cancer statistics, 2014. CA: a cancer journal for clinicians, 64 (2), 83-103 PMID: 24488779

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