When repair becomes disrepair
Cancer is a complex, multi-step process that can take decades to a lifetime to develop, during which the human body usually places a myriad of roadblocks in the path of a cell intent on forming cancer. The immune system, though not a focal point here, certainly stands as a line of defense against it. Fortunately, DNA repair, a clever strategy to erase the damage created by mutation or miscopying, serves as one of the obstacles that hold down fatal malignancies to a very low rate.
Just as you or I may make inadvertent mistakes when we make a hand-written copy of an original, the process of DNA replication also creates inadvertent mistakes. However, just as we can also correct the writing error with an eraser, the DNA repair machinery can instantly correct gene copy errors. We now know that several kinds of familial cancers are caused by inherited defects in DNA repair. Imagine the consequence that this defect would lead to if mistakes during DNA replication were no longer fixed properly. Let's again look at the example of colon cancer, this time from the perspective of DNA repair.
Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is an inherited disorder. It is characterized by the absence of polyp formation and attributed to hereditary mutation in a DNA repair gene. An individual suffering from HNPCC inherits a defective version of one of the four critical DNA repair genes. Therefore, in their cells, many of the DNA copying mistakes will remain uncorrected and be passed on as mutations to the daughter cells following cell division. As a result, over many cycles of growth and division, the cells of HNPCC patients accumulate mutations at an alarming rate.
Once again, the fundamental difference between this type of cancer and those sporadic (or non-inherited) cancers is the rate at which affected genes undergo mutations. In the colonic cells of an HNPCC patient, the absence of competent DNA repair machinery leads to a greatly accelerated rate of genetic mutation, and thus cancer development.
There is good news, however. The possibility of preventing or curing most colorectal cancer is now feasible; that is why it is imperative to promote broader public awareness and screening strategies among those with increased risks. HNPCC accounts for up to 5-6% of all colorectal cancer cases. Individuals with HNPCC have a lifetime risk of 70-80% for developing colorectal cancer, and women with HNPCC have a lifetime risk of 30-60% for developing uterine cancer, although the underlying mechanism remains unclear. It is also important to know that while the presence of a faulty gene can increase the risk of cancer, some people who inherit a defective gene never go on to develop cancer.
Since cancer cells carry mutated genes, the next question that arises is: how have good genes gone bad?
How good genes go bad
Our world is like a field with our bodies springing up from that field like plants, so our body needs nourishment and a healthy environment to grow and prosper. At the same time, we are surrounded by weeds —— viruses, X-rays, radiation, tobacco, alcohol, and toxic chemicals in our food, water, and air. These weeds or a toxic environment can lead to the demise of the plant. Incredibly, every human cell sustains thousands of mutagenic attacks everyday!
Carcinogens (i.e. cancer-causing agents, like X-rays, tobacco, toxic chemicals, or viruses) can enter our cells and bond with diverse target molecules inside. They can bond with DNA, and somehow alter DNA sequence, eventually damaging it. Once genes in a cell are damaged, the cell is no longer normal. This mutant cell will begin to grow uncontrollably within the body, sooner or later yielding a mass of descendant cells. The result: a tumor is created. Evidently, breathing in secondhand smoke caused damage to my dad's body that contributed partially to his lung cancer, as he used to work closely with a heavy smoking colleague for a decade or so.
All of us are equally vulnerable to cancer
Surely, the passing of a set of mutant genes through sperm or egg creates a hereditary susceptibility to cancer. Keep in mind, however, that the same genes, when mutated by random genetic accidents occurring throughout one's life, generate unpredictable cancers in more than 90% of the population. According to the National Cancer Institute, over 1 million individuals in the United States will have been diagnosed with cancer in 2009. Over 0.5 million Americans die of cancer each year. Tragically, many of those cases were preventable.
In summary, all humans carry genes that affect their predisposition to various types of cancer. While the roots of cancer lay deep in our genes and in our cells, cancer's ultimate causes really originate far outside the individual cell, in the environment where we live, in the food we ingest, and in the air we breathe. It has become abundantly clear that these factors, as reflected in our lifestyle, considerably influence cancer progression. We must address these ultimate causes of cancer before we can significantly lower the cancer incidence.
My father's death has taught me that, while we try to enjoy our lives, we need to be more vigilant about cancer risk factors, both obvious and subtle ones. Furthermore, of critical importance in cancer prevention is a healthy lifestyle, which substantially granted my father's prosperous life journey, and over which an individual can take control.
The ending can be a happy one: caring for our younger generations
Finally, as I contemplate the generations to come, it reminds me of how my dad loved and cared for not only his own children and grandchildren, but also other kids, including those of strangers.
Nearly 40 years ago when my dad had to take sick leave for his tuberculosis, he was able to spend more time with us and other kids in the neighborhood. One day he noticed a skin problem on a little girl who was brought to our neighborhood by her big sister to socialize with her classmates. My dad, being a doctor, urged her parents through the sister, to take care of her skin ailment. It appeared to be a peculiar ringworm (tinea in medical term). The girl's mom had already given up hope because all the doctors they had visited said that it was incurable. My dad, however, didn't give up. He went ahead, spending his own money despite our limited funds, and purchased the necessary medication for this little girl at the best hospital in the city. He then instructed her family in the method of topical treatment for the girl. After a period of time, the little girl's skin was completely healed. Her mom was very touched.... Needless to say, our two families, who didn't know each other before, became good friends resulting from my dad's genuine care for a stranger's girl.
References:
1. Offit, K., Brown K. (1994) Quantitating familial cancer risk: A resource for clinical oncologists. Journal of Clinical Oncology 12:1724-36.
2. Fearon E.R. (1997) Human cancer syndromes: Clues to the origin and nature of cancer. Science 278:1043-50.
3. Weinberg, R.A. (1998) One renegade cell: How cancer begins. published by Basic Books.
4. Garber, J.E., Offit, K. (2005) Hereditary cancer predisposition syndromes. Journal of Clinical Oncology 23(2):276-92.
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