Tuesday, January 04, 2011

Understanding Cancer

By Khaleel Ashraf, MD, DMRD, FACP

Dr. Khaleel Ashraf is a practicing Oncologist in Birmingham, AL and is associated with Hematology and Oncology Associates of Alabama, LLC located in Brookwood Medical Plaza.

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Few words in the English language cause as much anguish and anxiety as “Cancer”. Almost everyone seems to have had some brush with this often fatal disease either directly or indirectly. Unfortunately, this scourge is here to stay for the foreseeable future and remains one of the most deadly diseases in both developing and developed world (see Table 1):

Table 1. Cancer Incidence and deaths, 2010. National Cancer Institute SEER Database

 

That there are over 4000 patients diagnosed with invasive cancers and over 2000 deaths in a single day in United States alone shows how widespread is the problem. However, in a promising trend, implying treatment and surveillance advances stemming from years of research is finally paying off, mortality from invasive cancers decreased for the first time starting in 2003, at an annual rate of 1.6%. In terms of Cancer Prevalence, if one counts only those who have had cancer in the last 5 years, total number of people afflicted with cancer in US is over 4 million. If long term cancer survivors are also included in the count, the number of people afflicted with cancer in US goes above 10 million (11,196,431, to be exact,  per SEER estimate, 2010, see Table 2).

Table 2. Cancer Prevalence, 2010, National Cancer Institute SEER Database

Life time risk:

Assuming current trends, what is the likelihood of a newborn today developing some type of invasive cancer in his/her lifetime? Answer is uncomfortably close to a coin toss - lifetime risk for developing an invasive cancer is about 40%. For Asians, the risk is slightly lower, but not by much (35% or about 1 in 3 chance for diagnosis of an invasive cancer). The risk of dying from a cancer is about half of the risk of developing one (for example, the lifetime risk of dying from cancer for an Asian American, if current trends continue, is 18%).

Over the last several decades, there has been a real increase in the incidence and prevalence of many types of cancers. One common question I face as an oncologist when seeing a new patient diagnosed with cancer is “why me”. Sometimes the answer is obvious (heavy smoker who worked in a coal mine most of his adult life with lung cancer), but at times it is as puzzling to the doctor as it is to the patient – like the 40 year old mother of two, who only uses organic food and exercises regularly and “has done everything right” with kidney cancer. However, if you look a little deeper, it is amazing that clinically evident cancers do not occur more often. Just imagine this: DNA divisions during mitosis are not exactly error proof; simple base-pair mutations occur between one-in-one million to 1-in-10-billion for each cell division. With six billion base pairs in human DNA, that translates to between 1 and 6,000 errors per cellular division. Now, take in to account we are made up of roughly 50-75 trillion cells, and need to make several hundreds of billions of new cells each day (we need 10¹¹ or 100 billion new blood cells alone each day!). So the potential for a cell going “rogue” is, in fact, very high. In fact, at a cellular level, millions of cells capable of becoming clinically evident cancer develop in each of us almost daily. However, the body’s immune system and other in built defense mechanisms (the most important one being called “apoptosis” or programmed cell death, a cellular Hara-kiri where damaged cells commit suicide preventing it from becoming malignant).

However, once in a while the body’s defense mechanism gets overwhelmed and/or the apoptotic mechanisms go unhinged, and a cancer cell divides, and its progenies become large enough to become independent of the host’s control mechanisms. The time interval between the cancer diagnosis and the actual beginning of the cancer process can be months to years, as even with our sensitive technologies, it takes a tumor of about 1 cm to be seen on most imaging studies. A 1 cm tumor is made of about 1 billion cancer cells!

Unlike infectious diseases, where the onset of symptoms from the time of exposure is often days, and at most weeks, the duration between the putative cause(s) and the diagnosis of cancer are measured in years, often in decades. This makes accurate prediction of the etiological influence of many environmental agents difficult, if not outright impossible. One way scientists can get around this issue is to study temporal trends as well as to study geographical distribution of various cancers. The following graph shows how cancer deaths from stomach cancers have become less common in US during 20^th century, while cancer deaths related to lung cancer have increased significantly over the same period, helping to understand the role of various agents in causing cancer:

Cancer Death Rates*, for Men, US, 1930-2003

Cancer “Lingo”:

The common words used in describing cancer can be often confusing to patients and care givers. The term “tumor” is often used interchangeably with cancer, but by definition tumor does not necessarily mean cancer. Some tumors are “benign” – which, as the English word suggests, does not usually cause much of a problem unless it is located in a critical location like the brain, where, as one can imagine, even a “benign” tumor can cause significant problems. On the other hand, “malignant” tumors are always “cancerous” by virtue of their tendency to invade adjacent normal tissue and their ability to spread to distant organs by the way of metastasis. To make it more confusing, not all “cancers” are truly malignant, the most common examples being certain types of skin cancers like basal cell carcinoma, as well as non-invasive cancers of organs like the ductal carcinoma in situ which can affect the breast. Some types of very aggressive cancers do not have the word “cancer” in them (examples being Lymphoma, Melanoma, Myelodysplastic syndromes). One broad classification of malignancies is to divide them into three main groups depending on the origin of the cell/tissue: 

• Malignancy arising from epithelial lining cells is called “carcinomas”. Examples are lung cancer from the bronchial epithelium, breast cancer from the ductal epithelium, and these are the most common types of cancers.
• Malignancies arising from the “mesenchymal” tissue are called “sarcomas” and can affect structures like bones and muscles, and can often affect children and young adults.
• The third main class is malignancy of the blood and lymphatic system, which goes by names like lymphoma, leukemia, and myeloma, among others.

Etiology and Prevention:

Cancer is almost always multi-factorial, and often develops after years of exposure to environmental risk factors (chemicals, certain viruses). Certain genetic features make some individuals more susceptible to the environmental hazards more than others. For example, individuals with relative deficiency of one of the major anti-oxidant enzymes (glutathione S-transferase M1) are more prone for smoking induced cancers than who have normal levels of this enzyme. One easy way to suspect if you might be carrying an enzyme deficiency that make you more susceptible for a smoking agent induced cancer would be if you have a first or second degree relative with a smoking induced cancer. This does not mean that if you do not have a relative with smoking induced cancer you can smoke risk free! Smoking remains the number one cause of preventable or modifiable risk factor for many types of cancers, most commonly of the lung.

Most people are familiar with this relationship between smoking and chemical carcinogens and cancer. However, most of my patients are surprised to hear the increasing role dietary factors are playing in carcinogenesis. By an estimate by the National Cancer Institute, a jaw dropping 35% of all cancers may be related to diet! For example, diets high in fat have been linked to increased risk of various cancers, especially of the breast, colon, prostate, pancreas, ovary, and endometrium (USDHHS, 1988; National Research Council, 1989). Similarly, foods rich in red meat have been implicated in colon cancer. A metanalysis of several studies concluded that a high consumption of red meat increases colon cancer risk by as much as 28%, and a high consumption of processed meat increases risk by 20%. It is interesting to note that cancer incidence of various ethnic groups in US approach that of native population very quickly. For example, cancer risk for colon cancers and prostate cancers among Indian Americans are much higher than those who are in India, and closer to the incidence of Native Americans. This clearly shows that environmental factors and diet play and an even greater role in carcinogenesis than genetic and ethnic makeup.

On the positive side, several food items, especially fresh fruits, vegetables and legumes are known to have inherent anti-cancer properties. There are many examples of highly effective cancer medications derived from natural products like the widely used cancer chemotherapy drug Taxol, which is derived from bark of the Pacific Yew tree. It is possible we have only explored the “tip of the iceberg” in terms of naturally occurring cancer products. One huge area that is nearly unexplored is natural products from the ocean that may have anti-cancer properties. Eribulin®, a drug recently approved by the FDA to fight breast cancer, is derived from a sea sponge—and it has shown survival advantage in patients who have previously failed a median number of five different types of chemotherapy agents!

Indian food and cancer:

A topic that is especially relevant to us is how our particular diet may affect cancer incidence.

 

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