CANCER

The Basic Information You Need to Know in 1999

1. The Statistics-The Commonest and the Most Aggressive Cancers

More than 1.2 million newly diagnosed cases of cancer and 563,100 deaths from cancer are predicted for the United States during 1999. Lung cancer is the most common cancer, accounting for 15% of the cases and 28% of the deaths. The highest incidence rates for males and females are prostate and breast cancer respectively. Among males, the highest mortality rate is highest for lung cancer, followed by colorectal and prostate cancer, whereas among females the rates are highest for lung and breast cancers followed by colorectal cancer. Lung, colorectal, breast and prostate cancers are the four commonest cancers. When combined together, they account for 56% and 55% of the total cancer cases and deaths, respectively. All cancers show higher rates among men except for those of the breast, gallbladder, and thyroid gland. Worldwide, lung, stomach, breast, colorectal and liver cancers are the top five commonest cancers.

Ethnic variation exists for different cancers. For males, the rates for all cancers combined are highest in blacks, followed by whites and Hawaiian American, whereas for females the rates are highest for Hawaiian Americans, followed by whites and blacks. Whites have high rates for melanomas, lymphoma, leukemia and cancers of the lip, breast, uterus, ovary, testes, bladder, colon and rectum. Blacks have elevated rates for multiple myeloma and cancers of the oral cavity, esophagus, colon, pancreas, larynx, lung, cervix and prostate. Chinese Americans have increased rates for cancers of the nasopharynx and liver.

While it is true that cancer is more common in the elderly population, young people can also get cancer. In fact, cancer is the second leading cause of death among children aged 1 to 14 years in the United States. Leukemia, brain tumors, lymphomas, testicular cancers and soft tissue cancers are commonly seen in children and young adults.

The following represents some of the most aggressive cancers: lung, colon and rectum, pancreas, liver, stomach, esophagus, breast, kidney, ovary, thyroid and prostate. The mortality rates for these cancers are exceedingly high, particularly if they are at the advanced stages with metastasis. The leading 5 sites of cancer deaths for males in this country are: lung, prostate, colon and rectum, pancreas and non-Hodgkin’s lymphoma. For females, the leading causes of deaths include lung, breast, colon and rectum, pancreas, ovary and non-Hodgkin’s lymphoma.

2. The Major Causes of Cancer

Of the natural catastrophes that can befall us, the most distressing are those caused by our own behavior. At least 80% of cancers in Americans are caused by living habits and environmental carcinogens.

Among the carcinogenic hazards identified so far, tobacco smoking is the most important in Western countries and increasingly so in the developing countries. Smoking has been firmly linked to cancer not only of the lung but also of the larynx, mouth, pharynx, esophagus, bladder, and pancreas. The wide variety of cancers related to smoking is hardly surprising in view of the large number of chemicals detected in cigarette smoke and delivered to a highly vascular and absorptive organ. In the United States, it appears that smoking, especially of cigarettes, accounts for about 40% of all cancer deaths in men and about 20% in women. For smokers of two or more packs per day, the risk for lung cancer is about 20 times that of nonsmokers. As an oncologist, it is extremely disturbing to see the continued trend of increased smoking in China in recent years.

The benefits of stopping smoking have been demonstrated with lower risks relative to those of continuing smokers appearing within a few years of quitting. The introduction of lower tar levels in cigarettes and filtered cigarettes has also reduced the risk of lung cancer, although not nearly to the extent seen with cessation of smoking. The risks of cigar and pipe smoking are similar to those of cigarette smoking for cancers of the oral cavity, larynx, and esophagus, but are lower for lung cancer. Passive smoking has been debated as a risk factor for lung cancer. Evidence suggests that nonsmoking women married to smokers have experienced an increased risk, on the order of 30%.

Consumption of alcoholic beverages can potentiate the effects of tobacco smoking on cancers of the mouth, pharynx, esophagus, and larynx. In combination with smoking the risks multiply to 35-fold among heavy consumers of both products. Combined exposures account for about 75% of all oral and pharyngeal cancers. The risks are higher with hard liquors or beers than with wine. Alcohol is an important cause of hepatic cirrhosis, which is sometimes complicated by hepatocellular carcinoma. However, alcohol may also have an independent effect on the risk of this cancer.

Occupational Hazards and Environmental Pollution:

Occupational exposures appear to account for about 5% of all cancer deaths, although the proportion is higher in certain areas for particular cancers. Asbestos and inorganic arsenic are among the major occupational carcinogens in many countries.

About 5% of all cancer deaths may be attributed to radiation. The etiologic role of radiation was well established with the development of leukemias in populations exposed to the atomic bomb, in patients who were treated with radiotherapy and in radiologists prior to the advent of safety measures. The cancer risk appears to be higher if the same radiation dose is accumulated over a short period of time rather than over long periods.

Ultraviolet (UV) radiation from sunlight is the major risk factor for skin cancers, both squamous and basal cell carcinomas and melanoma.

Increased risks for the development of certain cancers have also been linked to medications. For example, long term use of oral estrogens have been implicated as an increased risk for endometrial and breast cancer. An excess risk for acute myeloid leukemia has been noted among patients receiving chemotherapeutic agents, especially melphalan, cyclophosphamide, and chlorambucil.

Several viruses have been implicated as the etiologic agents for certain cancers. The Epstein-Barr virus (EBV) is widely considered to be the cause of endemic Burkitt’s lymphoma and probably also of nasopharyngeal cancer. In certain areas of Africa, malaria appears to enhance the oncogenic effects of EBV and produce uneven distribution and occasional clustering of the Burkitt’s lymphoma. In southern China where the rate of nasopharyngeal cancer is high, the antibody titers in the affected patients are higher than in controls, suggesting a possible role of EBV in this cancer. However, other risk factors including consumption of salted fish or the presence of certain histocompatibility antigens appear to be involved as well.

Hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma, particularly in endemic regions of Asia and Africa. The risk for liver carcinoma was more than 200 times greater among carriers of hepatitis B surface antigen than among noncarriers in a large cohort study of 22, 707 men in Taiwan. Infection with hepatitis C virus may also increase the risk of liver cancer.

Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, has been linked to the high incidence of adult T-cell leukemia in some areas of Japan and the Caribbean. The human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome (AIDS), predisposes affected patients to Kaposi’s sarcoma and non-Hodgkin’s lymphoma.

Human papillomavirus (HPV), notably HPV-16 and HPV-18, has been implicated as a causative agent for cervical cancer. The DNA sequences have been found in a high percentage of biopsy specimens from invasive cervical cancer.

Genetic Predisposition: See below.

While it is true that most cancers are incurable, particularly if they are at advanced stages with metastasis, a few types of cancers can be cured. The majority of germ cell tumors and a great proportion of lymphomas can be cured even if they are at late stages. For most other types of cancers, cure can only be achieved by either surgery or radiation therapy if they are localized. This highlights the importance of early detection.

Cancer genetics is moving from an era of describing rare families in which there is an unusual aggregation of cancer to a more basic characterization of the molecular genetic events that underlie all cancers. In defining risk factors for cancer, one must consider the contributions of both genetic predisposition and environmental factors. A family history constitutes one of the most important risk factors for the majority of common cancers, for example, breast, colon, ovarian, and prostate cancer. With the development of molecular genetics techniques and the cloning of increasing numbers of cancer susceptibility genes, laboratory tests are being developed to detect predisposing genes. This has resulted in an improved ability to assess familial cancer risk and to identify individuals who would most benefit from genetic testing and counseling.

Although 90% of cancers are sporadic, more than 50 types of hereditary cancers have been identified. The important features of most hereditary cancers is the presence of one or more of the following: early stage of onset (often 10 to 15 years earlier than their sporadic counterpart);multiple primary cancers with specific patterns and combinations within patients and in families; bilaterality in paired organs; and marker phenotypes, for example, polyps in colon cancer. An important aspect of genetic testing is counseling of affected families, which serves to communicate the magnitude of the inherited cancer risk and to provide information on options for prevention and early detection.

Many cancer susceptibility genes have been identified and are being increasingly used in genetic testing. Among these the BRCA1 and BRCA2 for breast cancer, APC and DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2) for colon cancer are just a few examples.

Many studies have tried to link certain food components and micronutrients to cancer. However, due to inherent methodology difficulties and study design problems, most of the results are inconclusive. Nevertheless, increasing evidence has suggested certain dietary substances are associated with particular cancers. Increased dietary fat may be associated with breast and colon cancer. High total caloric intake has been implicated in breast, endometrium, prostate, colon cancer. Animal protein, particularly as red meat, may increase the risks for colon, prostate cancer. The consumption of salted fish containing high concentrations of nitrosamines has been linked to the high rates of nasopharyngeal cancer in Hong Kong and southern China.

The following dietary elements and micronutrients appear to reduce the risk of cancer: high fiber food; high content of vegetables, fruits and whole grain cereal; beans. Vitamin D may be protective factors for breast, colon and prostate cancers. Vitamin E and selenium may be helpful for prostate cancer.

The symptoms of cancer depend on the location and the size of the tumor, the substances released from the tumor. For example, cancer of the colon can cause abdominal discomfort, bowel habit change, and rectal bleeding. In addition, cancer can cause constitutional symptoms including fever, sweats, weight loss, poor appetite. In general, any unexplained symptoms lasting more than two weeks should prompt further evaluation by your physician.

Recognizing the risk factors associated with cancer, cancer prevention emphasizes the significant impact of changing long-standing patterns of behavior. The recommendations generally include cessation of smoking, restraint of alcohol consumption (in moderation if at all), avoidance of sun damage and change in dietary habits beginning in early life.

Recently, the concept of cancer chemoprevention has been developed. This is based on the notion that malignancies derive from a long, complex interaction between environmental stress and individual genetic phenotypic expression. Such intracellular stress ultimately results in multiple genetic mutations, causing loss of cellular growth regulatory control points, clonal expansion, and, ultimately invasion and metastasis. The goal of cancer chemoprevention is to identify the crucial molecular, biochemical, genetic, and environmental events prior to transformation and then to develop, test, and validate interventions that reverse or limit the genetic damage of these events. Cancer chemoprevention holds the promise that cancer may be treated prior to cellular transformation. Such treatment, if successful, will prolong the period of cellular transformation or eliminate altogether. Some of the promising chemoprevention studies include 1) retinoids prevent recurrence of head and neck cancers with a prior curative resection. 2) tamoxifen prevents breast cancer in women at high risk compared with a placebo control. 3) nonsteroidal antiinflammatory drugs such as aspirin and the new COX-2 inhibitors in the prevention of colon cancer.

Given the high mortality associated with advanced stage cancer, early detection and cancer screening have become a major public health issue. The goal of cancer screening is a very practical one-to detect cancer when it is early and treatable, if not curable. For a screening test to be useful, there must be a test or procedure that will detect cancer earlier, and there must be evidence that earlier diagnosis will result in an improved outcome. Several important features make particular cancers suitable for screening. These include 1) substantial morbidity and mortality, 2) a high prevalence in a detectable preclinical state, 3) the possibility of effective and improved treatment because of early detection, and 4) the availability of a good screening test with high sensitivity and specificity, low cost, and little inconvenience and discomfort. Although there are more than 100 different cancers, most of them lack proven screening interventions. Only cancers of the breast, cervix, skin, colon-rectum, prostate, and testes have widely accepted screening interventions, and there is controversy over some aspects of each.

The following is the general recommendations from American Cancer Society regarding cancer screening:

Breast Cancer: Mammography every 1-2 years between ages 40-49; every year age 50 and older. Monthly breast self-examination age 20 and older. Clinical breast examination every 3 three years ages 20-40; every year age 50 and older.

Cervical Cancer: Pap smear and pelvic examination yearly for all women who are, or have been, sexually active or who have reached age 18. After 3 normal smears, Pap test less often at the discretion of physician.

Colorectal Cancer: Digital rectal examination yearly after age 40; Fecal occult blood test yearly after age 50; Sigmoidoscopy every 3-5 years after age 50.

Prostate Cancer: Digital rectal examination yearly at age 40 and older. PSA yearly at age 50 and older.

Skin Cancer: No specific guidelines. However, general skin examination every 3 years for the general populations over the age of 20 years and more frequently for persons at risk.



9.  Cancer Treatment-The Multidisciplinary Approach

Cancer treatment involves a multidisciplinary approach. Surgery, radiation, chemotherapy, and hormonal therapy play different roles in the treatment of various cancers at different stages. In general, when cancer presents at early stages, either surgery or radiation therapy may be curative. However, patients with metastatic cancers are usually treated with either chemotherapy or hormonal therapy. For hematological malignancies (leukemia, lymphoma and multiple myeloma), chemotherapy will be the main treatment regimen. For end stage cancer patients, there is significant role for palliative care and psychosocial support. Recently, alternative medicine has gained increasing attention in cancer care.



10. New Development of Cancer Treatments

Modern molecular biology has revolutionized the new drug development for cancer treatment. With an increasing understanding of molecular mechanism of carcinogenesis and immune regulatory function, more drugs are designed based on the specific molecular targets. Recently, the monoclonal antibodies against lymphocyte surface antigen CD20 (Rituximab) and epidermal growth factor receptor Her-2/neu (Herceptin) have been developed and used in the treatment of lymphoma and breast cancer with success. More drugs that target signal transduction molecules, transcription factors, differentiation and apoptosis pathways and angiogenesis are currently in clinical trials. These new drugs coupled with the conventional chemotherapies should offer cancer patients with additional treatment options.

Although the diagnosis of cancer remains a daunting one to many patients and their family members, some general knowledge regarding the basic information of cancer should encourage people to modify their lifestyles, obtain early detection and routine screening when appropriate, and seek adequate treatment if they have diagnosis. Here are a few final recommendations:

		Quit smoking and restraint of excessive alcohol consumption. Avoidance of sun damage;
		Maintain a balanced low fat, high fiber, high vegetable and fruit diet;
		If multiple family members have diagnosis of cancer, particularly at young age, consider genetic counseling;
		Beware of unusual symptoms, especially if long duration;
		Maintain regular physician checkups and have age-appropriate screening tests;
		If diagnosed with cancer, consider a second opinion regarding treatment.