Life Extension Magazine®

The Colonoscopy Dilemma

Colorectal cancer is preventable if detected early, but still kills more than 57,000 Americans every year. Startling new findings conclusively demonstrate the benefits of flexible tube versus virtual colonoscopy.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in October 2024. Written by: William Faloon.

 
William Faloon

One of the most unpleasant methods used to screen for cancer is the colonoscopy. The procedure involves food deprivation the day before, along with the use of harsh laxatives. The following day, a specialist inserts a long tube up the rectum and pushes it through the entire colon to the appendix region. A somewhat similar technique was used during the Inquisition to extract information from suspected witches. It was a highly effective method of obtaining confessions.

Colon cancer treatment using colonoscopy or sigmoidoscopy to remove polyps (inset).

I had my last colonoscopy in September 2000. The doctors found one polyp, and that meant I was scheduled to have another colonoscopy in three years. As 2003 ended, I wondered if I really needed another colonoscopy after only three years. I was hoping I could find evidence that would let me wait five years like people without polyps do.

I searched the medical literature to ascertain the ideal interval between colonoscopies. Regrettably, the medical literature revealed that even more frequent screening is the prudent course of action.

The most compelling study showing the value of more frequent colonoscopies was published in the July 2, 2003, issue of the Journal of the American Medical Association (JAMA).1 This study evaluated 9,317 people who initially had negative sigmoidoscopies. When these same people repeated the procedure just three years later, a polyp or cancerous mass was detected in 13.9% of the study subjects. Based on this finding, the doctors who conducted this study raised concern that people who waited five years between colonoscopies could develop advanced cancer. A sigmoidoscopy examines only the lower third of the colon and the rectum. The consensus today is that doctors should conduct a full colonoscopy to examine and remove polyps from the entire colon and rectum.

If you are wondering why so many healthy people undergo this unpleasant procedure, a look at the grim statistics provides a persuasive argument. Cancer will kill about 563,000 Americans this year, with colorectal cancer accounting for about 57,000, or roughly 10%, of all cancer deaths.2,3 If you are a nonsmoker, your risk of lung, head and neck, pancreatic, and other cancers is significantly reduced. That makes colon cancer the type of cancer from which you are most likely to die, since the threat of contracting other cancers is so much lower.

I will discuss some startling new findings about the benefits of flexible tube colonoscopies versus virtual colonoscopies later. First, however, I am going to reveal some personal details to inform members on what I had to go through to get my latest colonoscopy performed this year.

While the American Cancer Society blames people for failing to take steps to detect cancer early, the fact is that it is becoming increasingly difficult to get medical procedures performed in an efficient manner. The result is that in today’s busy world, few Americans are taking practical steps to detect cancer in its early, curable stages.

MEDICARE NOW PAYS
FOR COLONOSCOPIES

Legislation passed in July 2001 provides coverage for all Medicare beneficiaries for average-risk screen-ing colonoscopy. Since that time, the number of average-risk screenings has increased from 4.6% before July 2001 to 14.2% after July 2001.4

The 14.2% figure still represents only a fraction of those Medicare beneficiaries who should have colonoscopies, which is one reason why colon cancer continues to kill about 57,000 Americans each year.

The Real Agony of My Colonoscopy
It is an established fact that most deaths from colorectal cancer could be avoided if more people were screened for colorectal cancers, especially high-risk individuals such as the obese and those with a family history of the disease.

While I am not overweight and do not have a family history, I would feel rather stupid if I were to contract advanced colon cancer just because I did not want to be inconvenienced by a colonoscopy.

The real agony, however, was dealing with the bureaucracy involved in arranging the procedure. First, there was the difficulty in getting through to the doctor’s office. Lots of busy signals, voicemails, and no returned phone calls. Then there were the insurance hassles, which we have all learned to expect for just about any medical procedure.

A big problem arose when the doctor insisted I first come in for a consultation, even though he had previously performed colonoscopies on me. I argued that there was no rational basis for a consultation when all I wanted was a colonoscopy. A consultation means wasted time driving to the doctor’s office, sitting in the waiting room for an hour, and sitting in the examining room for an additional thirty minutes, only to be told what day to return for the colonoscopy. I suspected that the doctor would earn a bigger insurance payment by squandering my time with a worthless consultation.

Despite my pleas to avoid the needless consultation, I was told it was required. I then resorted to finding a physician who had referred patients to this doctor. I convinced this physician to lobby the colonoscopy doctor to waive the consultation visit. It seemed like a significant victory when I received a call stating that I could have my colonoscopy without first wasting several hours on a needless consultation.

Unfortunately, the first appointment was more than two months away, and I was already overdue for this procedure. Again, I had the other physician lobby the doctor’s office to get an earlier appointment. The result was an appointment one month later.

Hold the Sedatives
A colonoscopy takes about 15 minutes to perform and can involve considerable pain and discomfort. That is why almost everyone is put on heavy-duty sedatives so that they are virtually asleep during the procedure. Some people insist on general anesthesia.

Because I do not have the luxury of missing a day of work just because of 15 minutes of pain, I routinely undergo agonizing medical procedures with no sedation. We are, after all, aging to death. I do not believe we have a day to spare not working to eradicate the aging problem. The advantage to my avoiding sedative drugs is that I am able to jump up from the table at the end of the procedure and immediately resume a productive schedule.

Doctors marvel at my insistence that no pain medication be administered. I respond that if I do not succeed in stopping aging, the agonies of aging will be a lot worse.

One Polyp Found
The result of my latest colonoscopy was the discovery of one polyp, which was cut out and removed during the procedure. While this means I will face this colonoscopy ordeal again in three years, at least this is one type of cancer I do not have to worry about for now.

As I related near the beginning of this editorial, a recent study revealed that 13.9% of people without any colon polyps would either have polyps or some sort of cancerous mass within the following three years. So, in reality, everyone over age 40 might consider a colonoscopy every three to five years. Based on the inconvenience, expense, and inefficiencies involved, it is no wonder that so few people undergo this procedure.

Polyps are considered precancerous lesions. Some of them develop into cancer. The medical establishment does not recommend routine colonoscopies until people reach the age of 50, yet approximately 13,000 people under the age of 50 will be diagnosed with colon cancer this year.5

Most doctors are not aware that so many people under the age of 40 die of colon cancer. A surprising number of children also die of colon cancer. The reason these young adults and children so often die is that their doctors do not suspect colon cancer because they are so young. Delayed diagnosis results in sharply higher mortality. If you are obese or have a family history of the disease, you should consider having a colonoscopy, even if you are under the age of 40.

TEXTBOOK DEFINITION
OF A COLONOSCOPY

A colonoscopy is a procedure in which a long, flexible viewing tube (a colonoscope) is threaded up through the rectum for the purpose of inspecting the entire colon and rectum and, if there is an abnormality, taking a biopsy of it or removing it. The procedure requires a thorough bowel cleansing to ensure a clear view of the lining.

Source: www.medterms.com.

Problems with Virtual Colonoscopy
People generally do not like long tubes shoved up their rectums. As a result, CAT scan centers have opened across the US. These centers offer whole-body scans and “virtual” colonoscopies—high-speed x-ray devices that take a radiographic picture of the inside parts of your body, including the lining of your colon. Commercial companies have invested big money in these expensive x-ray devices and tout them as being as good as flexible tube colonoscopy.

One drawback to virtual colonoscopies is that they expose the body to a lot of ionizing radiation. The reason that so much radiation is required is that a considerable amount of fat and water contained in the lower abdominal cavity has to be penetrated in order to get a picture of your colon. Some sources estimate that the radiation exposure from a virtual colonoscopy is equivalent to that of 500 chest x-rays (or 4.5 years of natural background radiation).6,7

Ionizing radiation damages DNA, which results in the mutation of genes that regulate cellular proliferation. Many different agents damage DNA, but the good news is that DNA has the capacity to repair and reverse most of this genomic damage. What makes ionizing radiation so dangerous is that it only takes one blast to the DNA to cause permanent gene mutation.8 That is why exposure to medical x-rays (that is, to ionizing radiation) can cause cancer. Those undergoing virtual colonoscopies to detect early-stage cancer could inadvertently be increasing their risk of future cancers because of radiation-induced gene damage.

Virtual colonoscopy: colon polyposis.

Another disadvantage of virtual colonoscopies is that if a polyp or other suspicious lesion is detected, then flexible tube colonoscopy has to be performed anyway. If flexible tube colonoscopy is chosen in the first place, polyps and suspicious lesions can be immediately removed and a biopsy can be done to ascertain if the mass is cancerous.

A study published in the April 21, 2004, issue of JAMA compared the accuracy of conventional (flexible tube) colonoscopy to virtual (x-ray-generated image) colonoscopy in detecting polyps. The sensitivity of virtual colonoscopy was only 39% and 55% for lesions sized at least 6 millimeters and 10 millimeters, respectively. These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99% and 100% for lesions sized at least 6 millimeters and 10 millimeters, respectively. In this study, virtual colonoscopy missed 2 of 8 cancers. The doctors who conducted the JAMA study concluded that virtual colonoscopy “is not yet ready for widespread clinical application…Techniques and training need to be improved.”9

Based on these data, those concerned about preventing colon cancer should choose flexible tube colonoscopy every three to five years, as opposed to virtual colonoscopy.

Dilemmas of Early Detection
Cancer phobia has become so prevalent that enormous amounts of money are spent every year on diagnostic procedures and lost labor productivity. If you develop any type of symptom that could possibly be cancer, and then enter that symptom into an Internet search engine, you will find multiple independent sources recommending that you run to a specialist to have the suspicious lump, pain, or other symptom investigated to rule out cancer.

Cancer diagnostic tests can be expensive, inconvenient, and sometimes dangerous. Yet the American Cancer Society urges that more Americans undergo these diagnostic procedures to reduce cancer mortality rates. We at Life Extension agree.

One problem is that there are not adequate economic or physician resources to provide all the cancer-screening diagnostics now being recommended by the government and various cancer organizations. It can take months to get a colonoscopy appointment. Just imagine if almost everyone who was supposed to have a colonoscopy decided that they would endure the inconvenience and undergo the procedure. The waiting list would swell to years, as there simply are not enough gastroenterologists to perform that many procedures.

With the aging of the population, more Americans are susceptible to cancer than ever before. The government is addressing this problem by encouraging Americans to eat large amounts of fruits and vegetables every day. Consumption of a wide variety of fruits and vegetables, along with reduced intake of carcinogenic foods, is considered a proven method of lowering cancer risk. The problem is that the amount of fruits and vegetables the government says is necessary to reduce cancer risk is beyond what is practical for most people to eat every day.

Dietary supplement companies offer products that contain concentrations of fruit and vegetable nutrients that may help to reduce cancer risk, but the government does not allow companies to advertise their products for the purposes of cancer prevention. The result is that many Americans do not supplement with the nutrients that are most likely to reduce their cancer risk.

For instance, supplementation with folic acid for 15 years was shown to reduce colon cancer incidence by 75% in the famous Nurse’s Health Study conducted at Harvard Medical School.10 The fact that 90,000 women participated in the study makes this finding especially significant. The authors explain that folic acid obtained from supplements had a stronger protective effect against colon cancer than folic acid obtained from dietary sources. Despite the findings from this prestigious study, the FDA does not allow folic acid to be promoted for the prevention of colon cancer.

While folic acid is contained in multivitamin products, the average American does not take many of the other probable cancer-preventing nutrients. These include indole-3-carbinol,11-25 selenium,26-31 chlorophyllin,32-41 curcumin,42-66 lycopene,67-74 lutein,75-84 green tea,85-105 gamma tocopherol,106-111 and a host of other plant extracts.

According to a report published by the National Cancer Institute on June 17, 2004, environmental factors contribute to 80-90% of all cancers. When using the word “environmental,” the Institute included both lifestyle factors such as diet and tobacco and alcohol use, as well as radiation, infectious agents, and substances in the air, water, and soil. The objective of this report was to show that the majority of cancers are preventable.112-113

In this instance, one government agency (the National Cancer Institute) states that 80-90% of all cancers are preventable and changes should be made to reduce cancer risk, while another government agency—the FDA—takes deliberate actions to suppress information about ways to prevent cancer.114

Why You Need the Life Extension
I discussed with several gastroenterologists the JAMA study indicating that performing colonoscopies more frequently might be desirable. To my surprise, not one of them knew about the study, despite its publication in a journal to which they all subscribe.

This kind of physician apathy is rampant in today’s health care system. Doctors often fail to read their own medical journals, neglect to implement new findings reported in the journals they do read, and fail to recommend any program (such as eating more fruits and vegetables) that would help prevent the very diseases for which patients are coming to them for screening.

Physicians are failing to incorporate the findings of published, peer-reviewed studies in their everyday medical practices. This means that patients are not gaining access to the latest information about better ways to prevent and treat disease.

Life Extension, on the other hand, reviews thousands of published studies each month to identify practical approaches people can take today to improve their health and reduce their risk of degenerative disease. We try to leave no stone unturned in our quest to provide members with scientific findings that can save their lives.

If you are relying solely on your doctors to keep you alive, you are probably missing critical information and innovative technologies that can improve your health. For many aging people, the result is a slow deterioration of their health right in front of their doctors’ eyes. While this mental and physical decline used to be considered an inevitable consequence of aging, people are increasingly rebelling against the dogma that says nothing can be done to impede age-related disease.

As a customer of the Life Extension, you gain access to cutting-edge technologies that are many years ahead of both conventional and alternative medicine. By reading this column, you just learned that virtual colonoscopies are only about 50% as effective as flexible tube colonoscopies in detecting colon lesions. This kind of information is priceless, and you receive over 100 pages worth of it every month in Life Extension magazine.

Life Extension is breaking down the barriers of ignorance that deprive aging humans of their good health. Readers of Life Extension Magazine® are often the first to learn about validated methods of detecting and warding off degenerative disease.

For longer life,
image

William Faloon

References
  1. Schoen RE, Pinsky PF, Weissfeld JL, et al. Results of repeat sigmoidoscopy 3 years after a negative examination. JAMA. 2003 Jul 2;290(1):41-8.
  2. Available at: http://www.cancer.org/ docroot/CRI/content/CRI_2_4_1X_ What_are_the_key_statistics_for_colon_ and_rectum_cancer.asp?sitearea. Accessed July 20, 2004.
  3. Available at: http://www.cancer.org/doc root/NWS/content/NWS_1_1x_ Medicare_Expands_Coverage_of_ Colonoscopy_Screenings.asp. Accessed July 20, 2004.
  4. Available at: http://www.congress.gov/ cgi-bin/cpquery/?&dbname=cp106&&r_ n=hr1033.106&sel=TOC_2545922&. Accessed July 20, 2004.
  5. Available at: http://my.webmd.com/content/ article/61/71439.htm. Accessed July 20, 2004.
  6. Available at: http://www.oncolink.upenn. edu/types/article.cfm?c=5&s=11&ss= 81&id=1728. Accessed July 20, 2004.
  7. Available at: http://www.newportbodyscan. com/radiationdosage.htm. Accessed July 21, 2004.
  8. Available at: http://physicsweb.org/article/ news/3/4/17. Accessed July 21, 2004.
  9. Cotton PB, Durkalski VL, Pineau BC, et al. Computed tomographic colonography (virtual colonoscopy): a multi-center comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. 2004 Apr 14;291(14):1713-9.
  10. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med. 1998 Oct 1;129(7):51724.
  11. Available at: http://www.lifeextension.com/magazine/ mag2003/jul2003_report_i3c_01.html. Accessed July 22, 2004.
  12. He YH, Friesen MD, Ruch RJ, Schut HA. Indole-3-carbinol as a chemopreventive agent in 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) carcinogenesis: inhibition of PhIP-DNA adduct formation, acceleration of PhIP metabolism, and induction of cytochrome P450 in female F344 rats. Food Chem Toxicol. 2000 Jan;38(1):15-23.
  13. Arif JM, Gairola CG, Kelloff GJ, Lubet RA, Gupta RC. Inhibition of cigarette smoke-related DNA adducts in rat tissues by indole-3-carbinol. Mutat Res. 2000 Jul 20;452(1):11-8.
  14. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000 Aug;78(2):123-9.
  15. Tiwari RK, Guo L, Bradlow HL, Telang NT. Osborne MP. Selective responsiveness of human breast cancer cells to indole-3-carbinol, a chemopreventive agent. J Natl Cancer Inst. 1994 Jan 19;86(2):126-31.
  16. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995 May-Jun;15(3):709-16.
  17. Jin L, Qi M, Chen DZ, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999 Aug 15;59(16):3991-7.
  18. Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated breast cancer cells. Oncogene. 2000 Nov 23;19(50):5764-71.
  19. Meng Q, Qi M, Chen DZ, et al. Suppression of breast cancer invasion and migration by indole-3-carbinol: associated with up-regulation of BRCA1 and E-cadherin/catenin complexes. J Mol Med. 2000 May;78(3):155-65.
  20. Cover CM, Hsieh SJ, Cram EJ, et al. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res. 1999 Mar 15;59(6):1244-51.
  21. Cover CM, Hsieh SJ, Tran SH, et al. Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem. 1998 Feb 13;273(7):3838-47.
  22. Manson MM, Hudson EA, Ball HW, et al. Chemoprevention of aflatoxin B1-induced carcinogenesis by indole-3-carbinol in rat liver-predicting the outcome using early biomarkers. Carcinogenesis. 1998 Oct;19(10):1829-36.
  23. Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991 Sep;12(9):1571-4.
  24. Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer. 1991 Mar 29;16(1):59-66.
  25. Shertzer HG, Berger ML, Tabor MW. Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol. Biochem Pharmacol. 1988 Jan 15;37(2):333-8.
  26. Yang CS. Vitamin nutrition and gastro-esophageal cancer. J Nutr. 2000 Feb;130(2):338S-9S.
  27. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996 Dec 25;276(24):1957-63.
  28. Davis CD, Uthus EO, Finley JW. Dietary selenium and arsenic affect DNA methylation In vitro in caco-2 cells and In vivo in rat liver and colon. J Nutr. 2000 Dec;130(12):2903-9.
  29. Finley JW, Davis CD, Feng Y. Selenium from high selenium broccoli protects rats from colon cancer. J Nutr. 2000 Sept;130(9):2384-89.
  30. Brooks JD, Metter EJ, Chan DW, et al. Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol. 2001 Dec;166(6):2034-8.
  31. Clark LC, Dalkin B, Krongrad A, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol. 1998 May;81(5):730-4.
  32. Ardelt B, Kunicki J, Traganos F, Darzynkiewicz Z. Chlorophyllin protects cells from the cytostatic and cytotoxic effects of quinacrine mustard but not of nitrogen mustard. Int J Oncol. 2001 Apr;18(4):849-53.
  33. Boloor KK, Kamat JP, Devasagayam TP. Chlorophyllin as a protector of mitochondrial membranes against gamma-radiation and photosensitization. Toxicology. 2000 Nov 30;155(1-3):63-71.
  34. Cho YS, Kim BY, Lee ST, Surh YJ, Chung AS. Chemopreventive effect of chlorophyllin on mutagenicity and cytotoxicity of 6-sulfooxymethylbenzo[a]pyrene. Cancer Lett. 1996 Oct 22;107(2):223-8.
  35. Dashwood RH. Early detection and prevention of colorectal cancer. Oncol Rep. 1999 Mar-Apr;6(2):277-81.
  36. Dashwood R, Yamane S, Larsen R. Study of the forces of stabilizing complexes between chlorophylls and heterocyclicamine mutagens. Environ Mol Mutagen. 1996;27:211-18.
  37. Egner PA, Wang JB, Zhu YR, et al. Chlorophyllin intervention reduces aflatox-in-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14601-6.
  38. Guo D, Schut HA, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylmida-zo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis. 1995 Dec;16(12):2931-7.
  39. Kumar SS, Chaubey RC, Devasagayam TP, Priyadarsini KI, Chauhan PS. Inhibition of radiation-induced DNA damage in plasmid pBR322 by chlorophyllin and possible mechanism(s) of action. Mutat Res. 1999 Mar 10;425(1):71-9.
  40. Kumar SS, Devasagayam TP, Bhushan B, Verma NC. Scavenging of reactive oxygen species by chlorophyllin: an ESR study. Free Radic Res. 2001 Nov;35(5):563-74.
  41. Smith WA, Freeman JW, Gupta RC. Effect of chemopreventive agents on DNA adduction induced by the potent mammary carcinogen dibenzo[a,l]opyrene in the human breast cells MCF-7. Mutat Res. 2001 Sep 1;480-481:97-108.
  42. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
  43. Chuang SE, Kuo ML, Hsu CH, et al. Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcino-genesis. Carcinogenesis. 2000 Feb;21(2):331-5.
  44. Churchill M, Chadburn A, Bilinski RT, Bertagnolli MM. Inhibition of intestinal tumors by curcumin is associated with changes in the intestinal immune cell profile. J Surg Res. 2000 Apr;89(2):169-75.
  45. Elattar TM, Virji AS. The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro. Anticancer Res. 2000 May-Jun;20(3A):1733-8.
  46. Mohan R, Sivak J, Ashton P, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem. 2000 Apr 7;275(14):10405-12.
  47. Park EJ, Jeon CH, Ko G, Kim J, Sohn DH. Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol. 2000 Apr;52(4):437-40.
  48. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 2003 Feb 1;101(3):1053-62.
  49. Chan MM, Fong D, Soprano KJ, Holmes WF, Heverling H. Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol. 2003 Jan;194(1):63-70.
  50. Chan WH, Wu CC, Yu JS. Curcumin inhibits UV-induced oxidative stress and apoptotic biochemical changes in human epidermoid carcinoma A431 cells. J Cell Biochem. 2003 Oct 1;90(2):327-38.
  51. Cheng AL, Hsu Ch, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or premalignant lesions. Anticancer Res. 2001 Jul-Aug;21(4B):2895-2900.
  52. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001 Jun 1;47(4):293-303.
  53. Galvano F, Piva A, Ritieni A, Galvano G. Dietary strategies to counteract the effects of mycotoxins: a review. J Food Prot. 2001 Jan;64(1):120-31.
  54. Gururaj AE, Belakavadi M, Venkatesh DA, Marme D, Salimath BP. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Commun. 2002 Oct 4;297(4):934-42.
  55. Hour TC, Chen J, Huang CY, Guan JY, Lu SH, Pu YS. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappa B activation. Prostate. 2002 May 15;51(3):211-8.
  56. Ichiki K, Mitani N, Doki Y, Hara H, Misaki T, Saiki I. Regulation of activator protein-1 activity in the mediastinal lymph node metastasis of lung cancer. Clin Exp Metastasis. 2000;18(7):539-45.
  57. Ikezaki S, Nishikawa A, Furukawa F, et al. Chemopreventive effects of curcumin on glandular stomach carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine and sodium chloride in rats. Anticancer Res. 2001 Sep-Oct;21(5):3407-11.
  58. Inano H, Makota O. Prevention of radiation-induced mammary tumors. Int J Radiat Oncol Biol Phys. 2002 Jan 1;52(1):212-23.
  59. Inano H, Onoda M. Radioprotective action of curcumin extracted from Curcuma longa LINN: inhibitory effect on formation of urinary 8-hydroxy-2’-deoxyguanosine, tumoro-genesis, but not mortality, induced by gamma-ray irradiation. Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):735-43.
  60. Kim DS, Park SY, Kim JK. Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from beta(1-42) insult. Neurosci Lett. 2001 Apr 27;303(1):57-61.
  61. Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol. 2002 Oct;21(4):825-30.
  62. Reddy BS, Rao CV. Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors. J Environ Pathol Toxicol Oncol. 2002;21(2):155-64.
  63. Shishu, Singla AK, Kaur IP. Inhibitory effect of curcumin and its natural analogues on geneto toxicity of heterocyclic amines from cooked food. Indian J Exp Biol. 2002 Dec;40(12):1365-72.
  64. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002 Jul 1;62(13):3868-75.
  65. Suryanarayana P, Krishnaswamy K, Reddy GB. Effects of curcumin on galactose-induced cataractogenesis in rats. Mol Vis. 2003 Jun 9;9:223-30.
  66. Khafif A, Schantz SP, Chou TC, Edelstein D, Sacks PG. Quantitation of chemopreventive synergism between epigallocatechin gallate and curcumin in normal, premalignant, and malignant oral epithelial cells. Carcinogenesis. 1998 Mar;19(3):419-24.
  67. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population [see comments]. J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92.
  68. Hsing AW, Comstock GW, Abbey H, Polk BF. Serologic precursors of cancer: retinol, carotenoids, and \tab tocopherol and risk of prostate cancer. J Natl Cancer Inst. 1990 Jun 6;82(11):941-6.
  69. La Vecchia C. Mediterranean epidemiological evidence on tomatoes and the prevention of digestive-tract cancers. Proc Soc Exp Biol Med. 1998 Jun;218(2):125-8.
  70. Narisawa T, Fukaura Y, Hasebe M, et al. Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene. Jpn J Cancer Res. 1998 Oct;89(10):1003-8.
  71. Pastori M, Pfander H, Boscoboinik D, Azzi A. Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochem Biophys Res Commun. 1998 Sep 29;250(3):582-5.
  72. Stahl W, Junghans A, de Boer B, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett. 1998 May 8;427(2):305-8.
  73. Weisburger JH, Dolan L, Pittman B. Inhibition of PhIP mutagenicity by caffeine, lycopene. Mutat Res. 1998 Aug 7;416 (1-2):125-8.
  74. Imaida K, Tamano S, Kato K, et al. Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis. Carcinogenesis. 2001 Mar;22(3):467-72.
  75. Ito Y, Suzuki K, Suzuki S, Sasaki R, Otani M, Aoki K. Serum antioxidants and subsequent mortality rates of all causes or cancer among rural Japanese inhabitants. Int J Vitam Nutr Res. 2002 Jul;72(4):237-50.
  76. Haegele AD, Gillette C, O’Neill C, et al. Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation. Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):421-5.
  77. Muhlhofer A, Buhler-Ritter B, Frank J, et al. Carotenoids are decreased in biopsies from colorectal adenomas. Clin Nutr. 2003 Feb;22(1):65-70.
  78. Levi F, Pasche C, Lucchini F, La Vecchia C. Selected micronutrients and colorectal cancer: a case-control study from the canton of Vaud, Switzerland. Eur J Cancer. 2000 Oct;36(16):2115-9.
  79. Slattery ML, Benson J, Curtin K, Ma KN, Schaeffer D, Potter JD. Carotenoids and colon cancer. Am J Clin Nutr. 2000 Feb;71(2):575-82.
  80. Sumantran VN, Zhang R, Lee DS, Wicha MS. Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid. Cancer Epidemiol Biomarkers Prev. 2000 Mar;9(3):257-63.
  81. Bidoli E, La Vecchia C, Talamini R, et al. Micronutrients and ovarian cancer: a case-control study in Italy. Ann Oncol. 2001 Nov;12(11):1589-93.
  82. Schiff MA, Patterson RE, Baumgartner RN, et al. Serum carotenoids and risk of epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control. 2000 Dec;11(10):965-74.
  83. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000 Jan 5;92(1):61-8.
  84. Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res. 1999 Mar 15;59(6):1225-30.
  85. Li HC, Yashiki S, Sonoda J, et al. Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Jpn J Cancer Res. 2000 Jan;91(16):34-40.
  86. Isemura M, Saeki K, Kimura T, Hayakawa S, Minami T, Sazuka M. Tea catechins and related polyphenols as anti-cancer agents. Biofactors. 2000;13(1-4):81-5.
  87. Jung YD, Kim MS, Shin BA, et al. EGCG, a major component of green tea, inhibits tumor growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer. 2001 Mar 23;84(6):844-50.
  88. Setiawan VW, Zhang ZF, Yu GP, et al. Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer. 2001 May 15;92(4):600-4.
  89. Tsubono Y, Nishino Y, Komatsu S, et al. Green tea and the risk of gastric cancer in Japan. N Eng J Med. 2001 Mar 1;344(9):632-6.
  90. Asano Y, Okamura S, Ogo T, Eto T, Otsuka T, Niho Y. Effect of epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia. Life Sci. 1997 Nov 29;60(2):135-42.
  91. Chen ZP, Schell JB, Ho CT, Chen KY. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett. 1998 Jul 17;129(2):173-9.
  92. Hibasami H, Komiya T, Achiwa Y, et al. Induction of apoptosis in human stomach cancer cells by green tea catechins. Oncol Repetition. 1998 Mar-Apr;5(2):527-9.
  93. Ito Y, Ohnishi S, Fujie K. Chromosome aberrations induced by aflatoxin B1 in rat bone marrow cells in vivo and their suppression by green tea. Mutat Res. 1989 Mar;222(3):253-61.
  94. Komori A, Yatsunami J, Okabe S, et al. Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol. 1993 Jun;23(3):186-90.
  95. Liao S, Umekita Y, Guo J, Kokontis JM, Hiipakka RA. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocate chin gallate. Cancer Lett. 1995 Sep 25;96(2):239-43.
  96. Naasani I, Seimiya H, Tsuruo. Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins. Biochem Biophys Res Commun. 1998 Aug 19;249(2):391-6.
  97. Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998 Mar;89(3):254-61.
  98. Otsuka T, Ogo T, Eto T, Asano Y, Suganuma M, Niho Y. Growth inhibition of leukemic cells by epigallocatechin gallate, the main constituent of green tea. Life Sci. 1998;63(16):1397-1403.
  99. Parshad R, Sanford KK, Price FM, et al. Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells. Anticancer Res. 1998 Sep-Oct;18(5A):3263-6.
  100. Paschka AG, Butler R, Young CY. Induction of apoptosis in prostate cancer cell lines by the green tea component, epigallocatechin gallate. Cancer Lett. 1998 Aug 14;130(1-2):1-7.
  101. Qin G, Gopalan-Kriczky P, Su J, Ning Y, Lotlikar PD. Inhibition of aflatoxin B1-induced initiation of hepatocarcinogenesis in the rat by green tea. Cancer Lett. 1997 Jan 30;112(2):149-54.
  102. Suganuma M, Okabe S, Kai Y, Sueoka N, Sueoka E, Fujiki H. Synergistic effects of epigallocatechin gallate with epicatechin, sunlindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9. Cancer Res. 1999 Jan 1;59(1):44-7.
  103. Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett. 1998 Nov 13;133(1):19-26.
  104. Valcic S, Timmermann BN, Alberts DS, et al. Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 1996 Jun;7(4):461-8.
  105. Matsukawa Y, Marui N, Sakai T, et al. Genistein arrests cell cycle progression at G2-M. Cancer Res. 1993 Mar 15;53(6):1328-31.
  106. Jiang Q, Christen S, Shigenaga MK, Ames BN. Gamma tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr. 2001 Dec;74(6):714-22.
  107. Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha tocopherol, gamma tocopherol, selenium and subsequent prostate cancer. J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23.
  108. London SJ, Stein EA, Henderson IC et al. Carotenoids, retinol and vitamin E and risk of proliferation benign breast disease and breast cancer. Cancer Causes Control. 1992 Nov;3(6):503-12.
  109. Nomura AM, Ziegler RG, Stemmermann GN, Chyou PH, Craft NE. Serum micronutrients and upper aerodigestive tract cancers. Cancer Epidemiol Biomarkers Prev. 1997 Jun;6(6):407-12.
  110. Smigel K. Vitamin E reduces prostate cancer rates in Finnish trial: U.S. considers follow-up. J Natl Cancer Inst. 1998 Mar 18;90(6):416-7.
  111. Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci USA. 1997 Apr 1;94(7):3217-22.
  112. Available at: http://www.cancer.gov/ newscenter/benchmarks-vol4-issue3/page1. Accessed July 23, 2004.
  113. Available at: http://progressreport.cancer. gov/doc.asp?pid=1&did=21&mid= vcol&chid=9. Accessed July 23, 2004.
  114. Available at: http://www.cancertutor.com/ WarBetween/War_Fda.html. Accessed July 23, 2004.