(Published in ENRICH magazine, 2022)
THE CONTENTIOUS CLAIM most adult cancers are due to "bad luck" or "malas" shouldn't be seen as a death sentence. Neither should it be regarded as a Gospel truth that deters us from doing all the good stuff proven to prevent cancer and extending our healthspans.
This unending hue and cry over the allegedly huge role chance (or is it Fate) plays in the development of cancer was triggered by a research paper published January 2015 in the peer-reviewed journal, Science. The paper suggested that cancer as a whole occurs by chance and can't be attributed mostly to heredity or lifestyle risk factors such as smoking and alcohol use.
The study asserts that two-thirds of adult cancers across different tissues are simply the result of sheer “bad luck”. Bad luck in this case refers to random DNA mutations occurring in genes that later progress into cancer. You're lucky if these mutations don't trigger cancer. If not, it's your bad luck.
These random and potentially harmful DNA mutations accumulate in our bodies when stem cells (cells that generate all other cells with specialized functions) divide into various tissues, explained Dr. Cristian Tomasetti, an eminent cancer biologist and an associate professor of oncology and biostatistics at Johns Hopkins University who is one of the study's two authors.
Dr. Bert Vogelstein, a professor of oncology and Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School, is co-author of the paper, "Variation in cancer risk among tissues can be explained by the number of stem cell divisions".
The study is a technical description of how cancer rates vary in different tissues and is based on data from the United States. It did not focus on cancer prevention or on lifestyle changes that deter cancer.
The study suggests our inherited genes, environmental factors and risky lifestyle choices such as smoking, alcoholism or eating too much red meat play a small role in cancer development.
"Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis," wrote Tomasetti and Vogelstein.
"These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions.
"The majority is due to 'bad luck,' that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes".
Tomasetti and Vogelstein found a strong relationship between how often certain cells divide in different kinds of human tissue and the lifetime chance cancer will develop in those tissues. They confirmed the more often cells divide, the more likely this tissue will develop cancer since duplicating DNA can lead to mistakes, and DNA mistakes can cause cancer.
Tissues with stem cells that divide a lot tend to develop higher rates of cancer. That's why colon cancer is more common than brain cancer. On the other hand, stem cells that rarely divide are likely to have lower cancer rates.
Vogelstein explained that cancer occurs when tissue-specific stem cells mutate or make random mistakes. These mistakes occur when one chemical letter (Adenine, Thymine, Guanine or Cytosine) in our DNA is incorrectly exchanged for another during the replication process in cell division. The massive accumulation of these mistakes over time increases the risk cells will grow unchecked into cancer.
"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Vogelstein.
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| Bad luck causes cancer |
Unlucky 22
A layman’s knee-jerk reaction to the “bad luck” conclusion is to ask "What's the use of a healthy lifestyle if there's practically nothing you can do to prevent cancer"?
Does this mean we should abide by the Epicurean blandishment to "Eat, live and be merry for tomorrow we die"? It's a tempting course of action given the study, but one that's wrong on all counts.
"If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," said Tomasetti.
Tomasetti and Vogelstein found that 22 of the 31 cancer types they studied could largely be explained by the "bad luck" of random DNA mutations during cell division. There are more than 100 types of cancer, of which carcinoma is the most common.
The 22 "bad luck" cancers identified by Tomasetti and Vogelstein are those in which “primary prevention measures are not likely to be as effective”. Primary prevention measures, which involve screening, seek limiting our exposure to carcinogens to prevent the start and spread of cancer.
They include lifestyle interventions (such as regular physical activity and not smoking) and medical interventions (vaccinations). Tomasetti and Vogelstein also said the early detection of cancer is a viable secondary prevention measure for some cancers that can't be overcome by prevention.
The other nine cancer types are due to bad luck plus environmental or inherited factors. These include basal cell carcinoma, HPV-16 (human papillomavirus-16) head and neck, thyroid follicular, lung (smokers), HCV (hepatitis C virus) hepatocellular, colorectal adenocarcinoma, Lynch colorectal and familial adenomatous polyposis or FAP colorectal.
Extrinsic factors
The conclusions of the paper by Tomasetti and Vogelstein are still hotly debated. The study continues to draw withering criticism and outrage from its foes, especially cancer prevention doctors who see it as negating the message that most cancers can be prevented. The furor has escalated with the publication of new studies seeking to counteract the "bad luck" hypothesis.
Eleven months after Tomasetti and Vogelstein's study, a team of cancer biologists and statisticians published a study in Nature, the British weekly scientific journal, detailing the contrary opinion using mathematical, epidemiological and molecular evidence.
“A majority of cancers are due to extrinsic factors,” declared Dr. Yusuf Hannun, director of the cancer center at Stony Brook University in New York State and senior author of the paper in response to the contention most cancers are the result of random biological mistakes.
“External factors can influence the rate of stem-cell division and the number of mutations", Hannun added.
The rebuttal explained that cancers are more prevalent than can be explained by cell division alone. This can be seen by the huge geographical variation in rates of different cancers, which suggest cancers are triggered by much more than intrinsic factors like cell division.
For example, prostate cancer is 25 times more common in Australia than south-central Asia (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka) while breast cancer is five times more common in Western Europe compared to East Asia (China, Japan, Mongolia, North Korea, South Korea, and Taiwan).
The Stony Brook study also said the non-inclusion of common cancers such as prostate and stomach cancer might have skewed the conclusion about the importance of cell division in explaining which tissues likely develop cancers. It pointed out cancers due to cell-division errors form the base to which cancers due to other causes are added.
The paper concluded that “unavoidable intrinsic risk factors (such as cell division) contribute only modestly, less than 10-30 percent, to the development of many common cancers”.
Doubling down
Partly in response to the Stony Brook study, Tomasetti and Vogelstein in 2017 released another paper (also published in Science) that defended their original findings and also sought to correct what they saw were widespread misinterpretations about it.
Based on health records from 69 countries, the new study argues that 66% of cancer-causing genetic mutations arise from the “bad luck” of healthy, dividing cells making random mistakes when copying their own DNA. This time, the new study admitted the cause of many cancers might be environmental factors.
It analyzed cancer genomes in a United Kingdom database to classify if cancer-causing mutations are hereditary, if they originate from the environment or are random DNA-copying mistakes.
Tomasetti and Vogelstein now pointed out their new conclusion does not mean that two-thirds of cancers can't be prevented. Vogelstein said understanding the role of unforced errors “could provide comfort to the millions of patients who developed cancer but led near-perfect (healthy) lifestyles”.
“This is particularly true for parents of children who have cancer” and who might blame the tragedy on the genes they passed on to their child or the environment they provided.
Hannun, however, was skeptical of the new study and remarked he wasn’t “very impressed with the overall conclusion”.
Cancer can be
prevented
Prevention still matters since some 42% of cancers are preventable. Tomasetti and Vogelstein admitted as much in their original study when they said "One of the most promising avenues for reducing cancer deaths is through prevention". They also said the early detection of cancer is a viable secondary prevention measure for cancers that can't be controlled by prevention.
We must take heart from the knowledge our chances of not developing cancer are affected by the lifestyle choices we make. We have to do the right thing. The Mayo Clinic, which has been consistently ranked among the best hospitals in the United States, offers these cancer-prevention tips.
* Don’t use any type of tobacco to avoid lung, throat, mouth, larynx, pancreas, bladder, cervix and kidney cancer.
* Maintaining a healthy weight and being physically active helps fight cancer. A healthy weight might lower the risk of breast, prostate, lung, colon and kidney cancer, among others. Physical activity might lower the risk of breast cancer and colon cancer.
* You've also got to go on a healthy diet by eating lots of fruits and vegetables. Also limit your intake of processed meats such as ham, bacon and frankfurters since eating lots of this stuff can slightly increase the risk of colorectal cancers and other chronic diseases.
* Regular medical examinations boost the chances of discovering skin, colon, cervix and breast cancer early on. Early discovery increases the likelihood of successful treatment of early stage cancer.
* Vaccinate yourself against Hepatitis B, which can increase the risk of developing liver cancer. Also vaccinate against the Human papillomavirus (HPV) that can lead to cervical cancer, squamous cell cancers of the head and neck and other genital cancers.
* Avoid risky behaviors such as unsafe sex with multiple partners to preclude acquiring sexually transmitted infections like HIV or HPV. People with HIV or AIDS are at a higher risk of cancer of the anus, liver and lungs. HPV increases the risk of cervical cancer, cancer of the anus, penis, throat, vulva and vagina.
* Protect yourself from skin cancer, one of the most common types, by avoiding the midday sun, staying in the shade and using sunscreen when needed.
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| Cancerous cells |
About cancer
Cancer, which can begin in almost any of the more than 37 trillion cells in the human body, is basically uncontrolled cell growth. A growing mass of cancerous cells can later develop into a tumor.
In the Philippines, 189 of every 100,000 Filipinos were afflicted with cancer in 2012. Four Filipinos died of cancer every hour or 96 cancer patients per day, according to a study conducted by the University of the Philippines’ Institute of Human Genetics, National Institutes of Health.
Cancer is one of the five leading causes of death in the Philippines with lung cancer due to smoking causing the most cancer deaths. Lung cancer caused by tobacco remains the biggest single cause of cancer deaths worldwide (six million deaths annually). There were an estimated 1.1 billion smokers on our planet in 2019.
The five most common cancers globally are carcinomas that attack organs and glands such as the lungs, breasts and skin. There's leukemia, which affects the body’s blood forming tissues. Sarcoma affects soft or connective tissues such as muscle, fat, bone and blood vessels.
Melanoma occurs in cells that pigment the skin. Lymphoma attacks the lymphatic system, which is part of the body's germ-fighting network.
Advancing age is the top risk factor for developing cancer with people over 65 running the greatest risk of acquiring the disease. The median age of a cancer diagnosis in the U.S. is 66 years-old.
For many of us, cancer will be in our future. One in two women and one in three men in the U.S. will develop cancer in their lifetime based on 2015 data. It’s equally grim in the United Kingdom where one in two men and women will be diagnosed with cancer. Cancer prevention starts now.
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