Preventive Medicine: Mostly Cancer By: Dr. Ronald Citron Tel: (707) 942-5818 Email Dr. Citron

INTRODUCTION

"We are under no illusion that preventive strategies will be easy to implement. For a start, the costs of prevention have to be paid in the present, while its benefits lie in the distant future. And the benefits are not tangible - when prevention succeeds, nothing happens. Taking such a political risk when there are few obvious rewards requires conviction and considerable vision." Kofi Annan

Less than 5% of smokers EVER get lung cancer. Surprised? 95+% of smokers light their cigarettes every day and never get lung cancer. Why? Answer: Genes and their control lie at the heart of this mystery, but we don't know exactly how. Ask the same question for colon cancer. One of the most common cancers in our country it, too, only happens in a small fraction of the population, with a lifetime risk of about 1 in 20 individuals (~5%). Why? What separates susceptible individuals from the rest of us? Less than 20% of colon cancer has a genetic (inherited) component. In the other 80% of cases of colon cancer, individuals have a problem with their own genome (the DNA in their cells). It all comes from the genes, the specific parts of DNA that encode cellular instructions, and their activity.

Cancer risk over a lifetime approximates1 in 2 for males and about 1 in 3 for women. Despite this, the overall incidence of any particular type of cancer remains relatively low. We must look at cancer not as one disease, but as many. Each has its own particular precursors, growth patterns and methods of treatment.

Scientists have discussed the causes of these terrible illnesses called cancer. We know now that not just one but many causes underlie this group of diseases. Thanks to Polymerase Chain Reaction (PCR), we can "Xerox" short pieces of DNA from just a few copies until we have a bucketful, enough material to reveal how cancer works and what we can do about it. We can use it to engineer specific diagnostic tests and therapeutics. In Medical Oncology, the advent of "targeted" therapies, molecules that specifically disrupt one particular metabolic reaction, already blend the descriptive and therapeutic phases of genomic biology.

Coupled with the power of computers, we make associations in the mass of data from the gene to clarify the role of selected genes in health and disease. Feats of technology such as this, unthinkable until recently, break new scientific ground every day.

Ultimately, preventive medicine promises to isolate and identify molecular and cellular uniqueness determinative of "getting" a disease or shielding us from it.

This chapter, written from the perspective of a medical oncologist, emphasizes the subject of preventive (and predictive) oncology. The greatest strides in medical science will soon be made in this field.

Let's separate Prevention from Screening: Prevention includes early knowledge of an increased chance of developing some disease, and efforts to avoid or nullify that risk. Screening encompasses the act of looking for an existing malignancy or a pre-malignant condition (e.g., colon polyp). For many cancers, early diagnosis saves lives.

Preventive Medicine comprises certainly more than just cancer prevention; avoidance of periodontal disease, seatbelt usage, vaccinations and other maneuvers to avoid life's tragedies, including diabetes and heart disease, also fall under its domain. However, surprisingly few recommended preventive measures exist outside of the field of cancer. Consider these helpful resources: www.uspreventiveservicestaskforce.org/uspstopics.htm and National Institutes of Health (www.nih.gov). You will find their suggestions later in this chapter.

RISK ASSESSMENT

Having hereditary cancer means carrying the gene, or genes, that puts one at greater risk for a particular cancer. Present from conception, these genes behave like a cocked gun. Very little stimulus needs to convert the possibility to a reality. Non-inherited cancers differ because they come about through genomic DNA changes after conception.

In this brief review we will look at risk assessment not only from the molecular point of view but also from the practical level: what dangers lie in wait and how to avoid them. For instance, viruses can make you sick with flu-like symptoms, yet some of the common viruses cause human cancers.

Stimuli to create cancer, such as smoking and viral infection, will not suffice. More metabolic changes must emerge to promote the cancer. Yet, cancer does not loom inevitably for those exposed. For that reason current methods of screening involve vast numbers of individuals, such as screening for colon cancer in everyone over the age of 50. Isolation and identification of the molecules allows medical oncologists to use them as triage, focusing on the relevant population at risk. Medical oncologists can use them to create specific, tailor-made, "targeted" therapies to correct the defect.

GENOMICS

This review can only touch on some of the material. For those with a science or biology sweet-tooth we urge outside reading on such things as: epigenetics, DNA repair, cell cycle, kinases, tumor suppressor genes, oncogenes, telomerase, and micro satellite instability, plus the basic scheme of how DNA is translated into a protein chain.

In the short time it takes to publish this book the body of genomic knowledge will have increased substantially.

Every nucleated cell in our bodies has a master molecule. It is DNA (deoxyribonucleic acid). DNA is two long strands of a chain of molecules entwined with each other in a firm embrace and divided into 22 pairs called chromosomes. If the DNA in only ONE cell in your body could be unwound it would stretch to six feet long! It would be a very thin, sub-microscopic six-footl length.

The function of DNA is mostly directing the making proteins (enzymes): the tools needed for cell functioning. The DNA in the fertilized ovum directs the growth and development of the human. The fertilized ovum contains all of the information to grow a whole human; from where the nose will be, to how the nerves grow to their final destination and how big the liver will become, to fingers - everything. We grow up and then stop, all controlled by our genes.

DNA analysis is the entryway to molecular prediction of disease, detailing of the health future of an individual, and making tools to cure or avoid illness. Dissecting the genes and looking for abnormalities will be part of screening procedures. It will take some time for all of the data to be collected and associations detected so that a meaningful gene scan can be done.

Currently a genomic test for risk for breast cancer recurrence is the first of these tests to get approval. However, it's not 100%. There is a portion (~10%) of early stage breast cancers that will go on to kill the patient. Looking at our current prognostic factors: histologic grade of tumor, size, node involvement, hormone and other receptors, we think that patients who have all of these low-risk characteristics should do well. Yet, 10% of them die from cancer.

This genomic information is extremely important information for the clinician, patient or individual. Now we can start to "strike through that pasteboard mask" separating phenotype, the visible characteristics of an organism, and genotype, the underlying genetic structure, its strengths and weaknesses.

The clinical risk factors for cancer described below make up the phenotype, the clinical factors, of the at-risk individual. For instance, the café-au-lait spots of Peutz-Jeghers Syndrome alert us to the possibility of certain gastrointestinal cancers that go along with the syndrome. Which of these individuals will end up getting cancer is determined by genotype and other cellular functions.

Other genomic tests are already being used commercially that look for risk of cancer and other non-malignant diseases. (See www.decodeme.com, www.navigenics.com, www.pathway.com, and www.23andme.com.) The tests offered commercially are not an exhaustive total gene scans but a cherry picking of genes where it is reasonably settled that there is a connection. The range of genes tested, limited at the current time, are still in the laboratory and not generally available.

The ideal to sequence everyone's genome (healthy or not) and make predictions based on an enormous database will arrive soon. Cost is, of course, an issue, and currently commercially available programs run from the low hundreds to low thousands of dollars per investigation.

Computer power and transmission speed will become increasingly important. Consider that the 1000 Genomes Project (www.1000genomes.org) has already compared the full genomes of 629 people to date. The combined information from this project is currently 7.3 Terabytes. This is 240 bytes or 1,000,000,000,000,000 bytes. Just to send this information to another site using a good connection would take 1 to 3 weeks!

Within the next decade, even sooner for some diseases, almost all of the information found in the Non-Genomic Risk section (below) will become a quaint reminder of another age.

NON-GENOMIC RISK FACTORS

Without genomic screening we look for clues in the history and physical exam that may alert one to potential or brewing problems. This clinical evaluation is often supplemented by imaging, tests of various cellular functions, specific metabolic reactions and, of course, when available, a thorough understanding of the individual genome that is in your exam room.

However, until the connection between diseases and the genome are known, we have these rather crude clinical methods. Like doing surgery with boxing gloves.

Examining these areas requires a skilled professional in the art of history taking and physical examination. For optimum results, the examiner should not feel rushed.

Gender:

Gender identification has greater importance than ruling out prostate cancer in women or breast cancer in men.

Overall, incidence and mortality is greater for males than for females across the tumor types with some exceptions.

• Women have a lower incidence of lung and bladder cancer because they don't smoke as much as men.
• Men have a higher incidence of oral cavity cancers, esophageal cancer, liver cancer, kidney cancer and melanoma, at least part in part explained by disparate incidences of tobacco use between the sexes.
• Women have a higher incidence of thyroid and gall bladder cancer.

Age:

Each decade of life has its own particular risks. There are specific cancers that strike infants, children and young adults. Heart attack strikes in the 40s, colon cancer in the 50s to 60s, Hodgkin's Disease in the late teens to early twenties, and breast cancer in the 50s to 80s. In general, getting older increases risk for many cancers and other diseases.

The exposure of youths to carcinogenic stimuli is probably very important but has received scant attention. Clues to this effect are clearly seen in young smokers: for the same amount of pack-years of smoking, risk increased as the age at starting smoking decreases. That is, the smoker who starts at 14 years of age is at greater risk than the smoker who starts smoking at 18. This should be a stimulus to studying other factors, such as diet, in childhood and adolescence. If diseases begin in childhood they end up being expressed as cancer in adulthood, and frequently late in life. This raises daunting obstacles because of the need of studying a cohort for decades, a cumbersome and expensive endeavor requiring uncommon dedication, determination and funding.

Ethnicity/Race:

The differences in disease incidence and prevalence among ethnic/racial groups indicate unique characteristics in the genome across the globe. In the United States there are differences, some of them extreme, in the incidence of cancer. (For up to date statistics see CA: A Cancer Journal for Physicians, Cancer Statistics issue; it is updated yearly.) The most striking differences across race are the incidence rates of multiple myeloma and prostate cancer, which are almost twice as high in African Americans as they are in Caucasians.

Occupation:

Industrial accidents, exposures and repetitive stress injuries are daily hazards to the work force. Much legislation and litigation has gone into the resolution of these problems. Many workers, when faced with a life threatening illness, consider the role of their job in the etiology of their disease.

Substances such as benzene, formaldehyde and asbestos are well known carcinogens. However, the disease must fit the exposure; asbestos causes cancers such as mesothelioma but not breast cancer. Benzene is linked with the occurrence of blood and bone marrow malignancies but not solid tumors such as lung or colorectal.

Issues of dosage, concentration of allegedly offending substances, chronology between exposure and onset of disease and biologic plausibility of an effect all come into consideration.

Nutrition:

Most authorities believe in a connection between nutrition and health. The role of fats in the diet is fairly settled as a cause of vascular disease. However, the strength of the association appears to be weaker between nutrition and cancer causation.

Obesity is the end result of our affluent malnutrition and promises to cause huge run-ups in health care costs. The incidence of obesity, diabetes, hypertension and orthopedic degeneration consequent to our national high calorie, high sugar, high salt and high fat diet is increasing rapidly. Heart disease is our number one killer, followed closely by cancer.

But for cancer the story is muddled. Why? Humans are not inbred and are too heterogeneous to be a good experimental animal. Effects of nutrition, like the effects of smoking, take decades to manifest - seriously hampering research efforts. Further, the effects may be modest and may not be seen in the statistical "noise" of human studies. Some factors may only work in conjunction with other unknown causes.

The effects of diet may be more potent during childhood and adolescence. Failure to consider this effect may seriously interfere with results of dietary studies done in adults.

There is some evidence that diet may affect: breast cancer (increased rates for obesity and alcohol), uterine cancer (increases in post-menopausal obesity), colorectal cancer (increased red meat and alcohol consumption), lung cancer (decreased risk from green and yellow vegetables) and prostate cancer (red meat increases risk, lycopene may protect).

The statistical strengths of most diet studies are modest, but the trend is in favor of protective effects of vegetables and fruits on overall good health.

Recommendation? Eat a diet similar to our hunter-gatherer ancestors; we have the same genes as they did. Eat a low-calorie mostly plant-based diet with a small amount of low-fat protein sources such as shellfish, fish and low-fat meats such as wild game - or farm raised, aves and ostrich. Make your children eat the same diet; don't give in to "easy" dietary fixes for them. Adults may consume alcohol after a discussion of the risks with their health care provider.

Hormones:

Hormones are critical to homeostasis of the organism, but they also have a role in carcinogenesis.

Effects can be seen in breast cancer depending on an increased or decreased exposure to estrogen and/or progesterone. Early menarche, late menopause, obesity and hormone replacement are associated with increased risk while an early age of first pregnancy and breast-feeding decrease risk.

For uterine (endometrial), cancers hormonal factors contribute either increased risk (estrogen replacement therapy, obesity, late menopause and sequential oral contraceptives) or decreased risk (pregnancy and combination oral contraceptives).

Ovarian cancer has a hormonal connection that relates to the total number of ovulations during a lifetime; the more ovulations the higher the risk. Early menarche and late menopause (also factors for breast cancer) increase risk while pregnancy and oral contraceptives (which stop ovulation) are protective.

Prostate cancer is a bit more problematic. Most authorities agree that the fuel for this cancer is testosterone, but exactly how is the key. For instance, treating a patient with an androgen (testosterone) blocker theoretically should decrease the incidence of prostate cancer. The experiment has been done and the incidence of prostate cancer was diminished 25%. But the decrease was in less aggressive cancers; the more aggressive cancers increased by 25% because the total number of cases was less.

Exercise:

The US Preventive Services Task Force recommends exercise. Although the benefits of exercise may be modest, studies consistently find that exercise not only reduces vascular disease and strokes but also decreases cancer risk.

Habits:

Two major habits, smoking and alcohol consumption, lead to cancer, either as unique carcinogens acting alone, or in synergistic combination.

At the top of this chapter I indicated that less than 5% of smokers get lung cancer. This shows the heterogeneity of carcinogenesis. This is not a license to smoke. Correlations between smoking and many cancers are firmly established, including: sinus, nasal, mouth, tongue, larynx, esophagus, pancreas, lung, colon, kidney, bladder, cervix and even breast cancer. More importantly smoking is an initiator and promoter of arteriosclerosis and causes heart attack, stroke, and generalized vascular insufficiency. Further, smoking is devastating to the structure of the lungs leading, in susceptible individuals, to emphysema and chronic obstructive pulmonary disease.

Alcohol is, at least, a co-carcinogen. When it is combined with smoking the areas where the streams of tobacco and alcohol collide including the mouth, throat and esophagus are especially susceptible to cancer.

Other habits, such as intravenous drug administration carry the dangerous possibility of infection that can create a major problem such as the AIDS virus or serious heart infection from shared or dirty needles and syringes.

Lifestyle risks most notably include sun exposure: recreational exposure in surfers and hikers and occupational exposure in personnel in telephone repair, pool maintenance, and other outdoor jobs.

Geography:

Areas in the United States have substantial differences in the incidence of specific types of cancer that have variably been ascribed to water, local food products, local industry and other causes. However, the causes are multifactorial, at least, and largely unknown. The incidence of melanoma, a disease caused by sun exposure, increases in lower latitudes.

Infections:

Viruses, bacteria and parasites are known causes of cancer. Most of these agents are oncogenic themselves whereas HIV (AIDS) causes malignancy through suppression and distortion of the immune system.

Most of the viruses involved are spread from intimate contact, including intravenous drug users with dirty or shared injection apparatus.

The Epstein-Barr virus is associated with Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal cancer, Burkitt's lymphoma, and Lymphoproliferative disease.

Hepatitis B and C viruses can cause liver cancer.

Herpes virus-8 can cause Kaposi's sarcoma.

Human papilloma virus can cause cervical and anal cancers.

Human T-cell lymphotropic virus type I can cause adult T-cell leukemia/lymphoma.

Helicobacter pylori, a bacterium, can cause stomach carcinoma and lymphoma.

There is no vaccine for Epstein-Barr virus, however there are vaccines available for Hepatitis B and human papilloma virus. H. pylori is readily treated with antibiotics.

Family History:

We think of family history as the equivalent of inherited disease. However, exposure It can be acquired through the habits and life-styles of family groups. For instance, diet is usually homogenous in a family group, and issues such as side-stream smoke and shared bathroom products and other items may be important.

Past medical history:

The patients' past medical history may be revealing. For instance, gastro-esophageal reflux can lead to Barrett's esophagus (a pre-malignant condition), and chronic untreated H. pylori infection may cause stomach cancer. Condyloma points to possible risk of cancer, especially cervical and anal. A history of polyp removal from the colon is an indication to follow-up on this pre-malignant condition. Undescended testicle is a risk factor for development of testis cancer. Careful questioning by an unhurried examiner is essential to unearth these important facts.

Hereditary cancer:

This is a large complicated issue that we can only touch on here. Hereditary diseases account for about 20% of all cancers. Family history and genetic testing should be considered for specific syndromes. Keep in mind that a patient with hereditary cancer could be the only family member to express the disease yet could pass it on to their progeny.

Space precludes discussion of the various hereditary cancer syndromes. I suggest a visit to; www.google.com, a very helpful search engine and www.wikipedia.org; also very rich and useful.

Iatrogenic Cancers:

Iatrogenic illness is caused by medical examination or treatment.

1. The risk of secondary malignancy de novo after cancer chemotherapy is increased. Risk is 14% higher in cancer survivors. In survivors of childhood cancer the risk may be six-fold. The earlier the first cancer occurs the greater the risk of future cancers.
2. Radiation therapy to the pelvis leads to an increased risk of bladder and rectal malignancies. Radiation to the left side of the chest (as done for breast cancer) comes with a higher risk of coronary problems.
3. Endocrine dysfunction, sometimes permanent, will change quality of life for some. Hypothyroidism, for instance, can result from radiation therapy to the upper airway.
4. Sterility, either temporary or permanent, happens during courses of some chemotherapy.
5. Diagnostic imaging using radiation or radioactive pharmaceuticals is extremely common. We have recently seen reports of significant over exposures from diagnostic and therapeutic radiation sources. Some of these were machine errors and some were operator related.

Socio-economic Status:

Socio-economic factors are difficult to pin down. Lower socioeconomic status is closely associated with tobacco, poor nutrition, alcohol consumption, obesity and lack of education leading to poor health habits and lack of appropriate medical care, including screening.

Innumeracy:

The statistics of risk are frequently misunderstood or presented in such a way as to elicit an emotional reaction. For instance, if I told you that if you chew betel nuts (a carcinogen) your risk of getting oral cancer is increased three hundred percent, how would you react to it? This is relative risk.

But it doesn't tell you the whole story. We could look at absolute risk: the number of people out of 100,000 who will get the disease. Absolute risk of oral cancer it is ~3.8 per 100,000 people. And a three-fold risk would be 11.4 out of 100,000 people.

Another way to quantify risk is to look at the percentage chance of acquiring the disease. For instance, in the above example the risk rose from 0.0038% to 0.0114%.

All the above calculations are equivalent. Yet the different ways of conveying the same information have disparate emotional impact.

SCREENING

Trying to identify patients with a particular illness by testing everyone has the disadvantage that the global costs of screening are so large that they would crash the system. Colonoscopy, the gold standard of screening for colon cancer and pre-malignant polyps, is so costly that some policy makers continue to advocate for the use of sigmoidoscopy, or less, as an alternative.

Can we refine our search by eliminating the need to minutely examine everyone to detect disease? Can't we look for molecular surrogates that will warn of the danger of a condition? Of course; and that is where are heading at ever increasing speed.

At the current time, as a matter of public policy and good medical sense we encourage screening and testing for particular diseases. There has to be a demonstrated benefit. Yet, who should get screened? What methods should we use? When should screening start? Should it ever stop?

Who shouldn't we screen? Currently we don't screen for cancers: where the outcome is dismal at any stage (such as pancreatic cancer), where good screening methodology is not available, where screening has yet been shown to be cost effective (ovarian cancer, for instance) despite tests that can detect abnormalities.

Other issues must be considered in a screening program:

• questions about incidence: is the cancer sufficiently prevalent to suggest a screening program?
• questions of cost-effectiveness. Can we afford it? Who is "we"? How many lives will be saved.
• questions of cost. Who will pay?
• questions about false-positives. What proportion of patients with a positive screenings only to find, on further examination, a benign lesion? What are the financial costs of false-positives? What are the emotional costs of false-positives? Lung cancer screening is a good example of this problem.
• questions about malignancy. Some pre-malignant and even some malignancies may never injure the patient. Prostate cancer is a good example of this problem.

Cancer of the Cervix: In the mid 20th Century every woman, starting at menarche, had a Pap smear annually. After a while it was realized that women who have three or more consecutive negative Pap's probably wouldn't get cervix cancer and the authorities relented a bit, and suggested every three year screening.

We know the cause of the majority of cervical cancers: Human papilloma virus (HPV). Only a few of the many strains of HPV are the cause of cervical cancer (esp. 16 and 18). This virus is spread by sexual contact. Screening only HPV positive patients for cervical cancer would seem reasonable.

A vaccine is commercially available and recommended for all sexually active females. Invasive cervical cancer is not a common cancer. With an incidence of only 12,000 new cases per year, universal vaccination should extinguish the disease.

Who doesn't need a Pap smear? Based on current practice the answer seems to be "No one." There is no need for Paps in women who don't have a cervix UNLESS they have a history of pelvic malignancy. Yet 10 million Pap smears are done yearly on women who have no cervix! (For more on this fascinating subject see: Cervical Cancer Screening Among Women Without a Cervix Brenda E. Sirovich, H. Gilbert Welch JAMA (Journal of the American Medical Association) Vol.291: pages 2990-2993)

Breast cancer: Currently screening is done by mammograms. Breast self examination is no longer a favored procedure because mammograms are much more sensitive. The American Cancer Society recommends examination by a qualified health care professional on an every three-year basis from age 20-30 and then yearly thereafter. Other issues involve the appropriate time to start and also when to stop.

Experts still differ about the precise recommendations; for instance, the US Preventive Service Task Force recommends mammograms starting at age 50 to age 74, while the American Cancer Society advises starting at age 40 with no upper limit.

What about women with dense breasts? Women with radiographically dense breast tissue are at a major disadvantage because the mammogram cannot adequately penetrate the dense breasts, which might be hiding an abnormality. Dense breast tissue is, in itself, a risk factor. Solution? An MRI of a breast shows detail unavailable from conventional mammography. Although costly, the cost benefit ratio is strongly in favor of the procedure for women with radiographically dense breasts. It is also recommended in patients who carry or have a relative who carries the breast cancer gene (BRCA), because they have a 20-25%or greater risk of breast cancer based on current models or dense breasts.

Colorectal Cancer: Colorectal screening is well established. However, the methodologies used have led to confusion and disagreement as to the best method or approach.

What do we look for when screening the colon? We look not only for cancer but also for precursor lesions such as polyps and villous adenomas, plus many other conditions. A polyp has a risk of turning into cancer. The removal of a polyp (a relatively simple procedure done during screening) has two advantages: first, polypectomy removes the threat of cancer occurring in that polyp; second, it alerts the clinician that this patient is a polyp former and should have a shorter screening interval.

The problem of how screening is accomplished is at issue.

Colonoscopy, most experts conclude, is the gold standard of screening. A clean colon can be minutely examined from the ileo-cecal valve to the anus. However, a great number of people are screened by sigmoidoscopy instead. Polyps can occur anywhere in the colon. X-ray contrast imaging of the colon may be used as an alternative, but when an abnormality is found the patient will still have to undergo colonoscopy. Why not go for the gold and do colonoscopies on all people over the age of 50 (the traditional starting time for screening)? Some experts answer that the procedure is so expensive that the health care system could not take the economic hit. The magnitude of the therapeutic value is at issue.

This is a perfect example of the need for molecular triage. Currently standards advise screening ALL people over 50 for colon cancer. Yet, as we know, only a few of this group will have a cancer or polyp diagnosed. The hope is that in the future there will be a blood test based on genomics that will allow us to concentrate on those individuals truly at risk.

Prostate Cancer: Prostate glands make a substance called prostate specific antigen (PSA). When the prostate becomes cancerous the PSA blood test increases into the abnormal range. This test has revolutionized prostate cancer detection and thoroughly confused its management.

Significant controversy occurs when an elevated PSA is found. First, there are false-positives: normal prostate cells making PSA because they are infected or irritated. Illnesses such as benign prostatic hypertrophy (BPH), inflammation or infection can also raise the PSA into the abnormal range.

Second, and perhaps more importantly, prostate cancer is a disease mostly of older men. Prostate cancer rates increase with age; they are regularly found at autopsy on asymptomatic patients who have died of unrelated causes. Many more men die with prostate cancer than of prostate cancer.

Are we treating patients who don't need therapy? The consensus seems to be that we are. However, younger patients, patients with good (>10 years) life expectancy, aggressive tumors and African Americans are treated preferentially. The evaluation of the life expectancy is key to treatment decisions. Tumor grade and stage are some other factors that influence treatment decisions.

A patient who has a diagnosis of prostate cancer is usually motivated to treatment. Radiation therapy or surgery (the two standard treatments) brings complications: incontinence and impotence are common and not trivial problems. In addition, radiation can have devastating effects on bowel and bladder function.

Authorities now recommend that before PSA screening the doctor should get informed consent to do the test, after a detailed discussion of the pros and cons of the exam and its implications.

Lung Cancer: Screening for this cancer brings up a fundamental problem with current screening. Our methods have become so sensitive that we find lesions are so small that we cannot distinguish between the image of a benign lesion and a malignancy, nor can we currently biopsy tiny lesions. In a recent, well-received report, the National Lung Screening Trial reported its results. Spiral CT scans of smokers reduced death from lung cancer by 20%. However, it has been estimated that a third of the participants would come up with false positive findings necessitating further invasive procedures with their risk for complications.

The other big issue is - drumroll please - economics. Currently, third parties do not cover this screening procedure unless the scan is done because of symptoms.

METABOLIC FACTORS

We have sets of enzyme systems in our bodies that help us metabolize various substances - carcinogens, chemicals, pharmaceuticals, and foods. They are molecules whose over or under expression may protect or increase risk for disease. Three families of enzymes are: 1) Cytochrome P450 series (CYP, important in steroidogenesis and detoxification), 2) Glutathione - S - transferases (GST, detoxification) and 3) N-acetyl transferases (NAT, detoxification, esp. of drugs).

Over or under expression of these enzymes seem to have consequences relative to some cancers and other diseases. This kind of analysis starts to get into the heart of prevention by its ability to identify people who are at risk because of metabolic and molecular factors. Although the associations are valid this technique has not caught fire with clinicians. Why? Because risk of getting disease based on these markers is not mature enough to be statistically powerful in prospective analysis.

CURRENT RECOMMENDATIONS FOR PREVENTION OF NON-MALIGNANT DISEASE

From US Preventive Services Task Force

1. Exercise may be the single most important activity one can do to maintain good health. A brisk 20 to 30 minute walk several (3+) times per week is recommended.
2. Diet is an essential element for healthy living. Low fat, low calorie composed mostly of plant food plus a good source of non-fat protein (birds, fish, shellfish).
3. A baby aspirin (81 mgm) taken on a daily basis is encouraged for men between the age of 45-70, and in women ages 55-79, unless you have a known sensitivity to aspirin.
4. Blood pressure should be measured at physician visits.
5. Pregnant women should: be screened for bacterial vaginosis; take 400-800 micrograms of folic acid per day; have Rh type determined; encouraged to breast feed; tested for bacteria in the urine at 12-16 weeks; tested for Chlamydia, syphilis and hepatitis B.
6. Newborns should be: tested for hearing loss at birth; given ocular prophylaxis for ophthalmic gonorrhea; and given appropriate vaccines.
7. Children between 3 and 5 should be tested for visual acuity.
8. Sexually active individuals should be tested for sexually transmitted diseases such as Chlamydia (under age 24), gonorrhea, and HPV.
9. HIV and syphilis testing should be done in individuals practicing high-risk sex.
10. Diabetes - testing only for adults with a blood pressure over 135/80(!)
11. Depression - recommendations are to screen only if support is available!
12. Males between ages 65-75 with any history of smoking should be screened for aortic aneurysm.
13. All adults over the age of 35 should be tested for lipid disorders: earlier if at an increased risk.

According to the US Preventive Service Task Force prevention or early diagnosis many strategies have been determined to lack sufficient evidence for general use. For instance, wearing seat belts, screening for heart disease, coronary artery stenosis and screening for COPD (chronic obstructive pulmonary disease) are not recommended, yet continue to be used in routine daily medical care.