How Cancer Begins

The Answer to Cancer
by Carolyn D. Runowicz, M.D., Sheldon H. Cherry, M.D., Dianne Partie Lange

(Page 2 of 2)

As complicated as cancer is, and as confusing and complex as the names of the many different kinds of cancer are, the simple fact is that the disease begins with a single cell. From there, it follows a well-choreographed process consisting of three key steps: initiation, promotion, and progression. Each of these plays a crucial role in cancer prevention. In particular, measures such as risk control, early detection, and chemoprevention are likely to be most effective during the first two steps.

The following discussion gets a bit technical, so you may want to skip over it for now and come back to it when you're reading about a specific aspect of cancer prevention. It provides the necessary background for understanding why some things protect against cancer and, perhaps equally important, why other things don't. If you understand how the disease develops in the first place, you'll be better able to take action to lower your risk.

Initiation

All cancers begin with a mistake within a cell's chromosomes, which serve as the containers of the cell's genetic material, or DNA (short for deoxyribonucleic acid). The mistake may appear in the chromosome itself, or it could turn up in a gene-a segment of DNA-within the chromosome.

DNA consists of a long chain of chemicals tightly wound within the chromosome. The strands of DNA in each of our 23 pairs of chromosomes contain between 30,000 and 40,000 genes.

While a mistake, or mutation, in a gene may be inherited from a parent, it's more likely to occur spontaneously in the course of cell division. Or it could be the result of some external factor. A physical injury such as bombardment with radiation can cause a mutation. So can a viral infection or chronic inflammation. For example, in ulcerative colitis-inflammation of the intestinal tract-cells divide very rapidly, increasing the possibility for error. A mutation also can be linked to a chemical, like the ones in tobacco smoke.

Chromosome with DNA

DNA (deoxyribonucleic acid) is a thread of four precisely ordered CHEMICALS COILED UP WITHIN EACH CHROMOSOME IN A CELL'S NUCLEUS. (EACH CELL CONTAINS 46 CHROMOSOMES.) THE FOUR CHEMICALS THAT MAKE UP DNA JOIN EACH OTHER, FORMING A TWISTING, LADDERLIKE STRUCTURE DESCRIBED AS A DOUBLE HELIX. UNITS OF DNA ALONG THIS LADDER, OR GENES, CONTAIN A CODE THAT INSTRUCTS THE CELL TO MAKE A SPECIFIC PROTEIN.

Anything that's responsible for triggering a genetic mutation that eventually can turn into cancer is known as an initiator or a carcinogen. You'll learn more about carcinogens in part 2, when we discuss specific cancers.

The good news is, most of the mutations that affect DNA are corrected by the body's built-in repair mechanisms, which also are under genetic control. The injured DNA can be replaced with a healthy section, using what might best be described as a cellular patch kit. Enzymes that remove certain kinds of damage travel to the site of the mutation to make the necessary repairs.

Unfortunately, mutations also can occur in the genes that govern these repair mechanisms, as well as in the genes that control a cell's growth or death. In particular, mistakes in the genes responsible for cell growth, called oncogenes, can lay the groundwork for cancer. This is because as mutations accumulate, the opportunity for oncogenes to become hyperactive increases as well. A protein that's produced by oncogenes instructs cells to reproduce endlessly.

So far, scientists have identified more than 100 different oncogenes. Usually several take part in the cancer process. Sometimes they're switched on by external factors, such as substances in tobacco smoke and the ultraviolet radiation in sunlight.

Some oncogenes tend to be associated with certain cancers. One example is RAS, an oncogene that plays a role in colorectal cancer.

Mutations even appear in genes whose sole purpose is to stop tumors from forming and/or growing-hence the name tumor suppressor genes. One such gene that is especially well-known to cancer researchers is the p53 gene. A mistake, or mutation, in this gene is present in more than 50 percent of all tumors. You'll learn more about the p53 gene, along with the 17 or so other tumor suppressor genes, later in this book.

Promotion

For cancer to develop and grow, two events must take place: a change in a gene that affects cell growth, and exposure to something that promotes cell growth. This so-called two-hit theory explains why not all women who inherit a breast cancer gene actually develop breast cancer and why not all smokers get lung cancer.

More than likely, several genetic mutations are necessary to trigger cancer. As scientists continue to discover and map genes, they also will be able to determine which combinations of genetic errors affect a person's cancer risk.

A promoter is something that speeds up the pace of cell division, which can create more genetic mutations and deliver the second hit that leads to cancer. A promoter may be a hormone such as estrogen or a toxic substance such as a chemical in tobacco smoke. Researchers believe that obesity and poor diet may act as promoters, though the mechanisms behind them aren't clear. Some factors, like radiation, can play the dual roles of initiator and promoter.

Fortunately, from a prevention point of view, some substances can interfere with cancer promotion. For instance, certain types of dietary fiber curtail the absorption of carcinogens in the intestine. In laboratory experiments, antioxidants such as vitamins A, C, and E act as anticarcinogens. On the other hand, deficiencies in these nutrients may contribute to certain cancers.

The cancer process still can turn around at the promotion stage, depending on the amount of genetic damage. But scientists don't know for certain when this window of opportunity closes. Until they can answer this question, avoiding promoters remains an important aspect of cancer prevention.

Progression

The term progression refers to the out-of-control growth of abnormal cells that is the basis of all cancers. As explained earlier, the cells accumulate to form a tumor, and the tumor keeps growing, possibly extending into adjacent tissues. In addition, cells may spread to other parts of the body, forming clusters there.

How quickly a cancer progresses is determined in part by genetic programming. It also is influenced by conditions in the body, such as the presence of certain hormones. Even once progression begins, a vigilant immune system still may destroy cancer cells, significantly interfering with the disease process, if not stopping it entirely. Cancer growth may be so slow that the malignant cells never cause a problem. In support of this fact, it's estimated that cancer is present in the organs of 10 to 15 percent of people who die from other causes.

Prevention Is Paramount

Now that you have a basic understanding of what's involved in the cancer process, you can see how prevention could be your best defense against the disease. You have many options for stopping cancer before it gains a foothold. For instance, you can limit your contact with substances that initiate or promote the disease. You can enhance the body's immune defenses and cellular repair systems. Pinpointing and treating precancers offer another avenue of attack. So, too, does turning on or off the various mechanisms that drive cell growth.

Some of these preventive measures are available now. Many more are on the frontier of cancer prevention. We'll explore them in depth in the chapters that follow.

© 2004 by Carolyn D. Runowicz, M.D. and Sheldon H. Cherry, M.D.

About the Author

Carolyn D. Runowicz, M.D., currently serves as directory of the University of Connecticut Cancer Center in Farmington. She is second vice president of American Cancer Society and past president of the Society of Gynecologic Oncologists, the woman to hold the post.

Sheldon H. Cherry, M.D., is clinical professor of obstetrics and gynecology at Mount Sinai School of Medicine in New York City.

Dianne Partie Lange, is the former editor-in-chief of Natural Health magazine and a former syndicated health news columnist for the Los Angeles Times. She resides in Carnelian Bay, California.