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International Updates

Cancer

Issue 78

HUNCHAREK and colleagues, Department of Clinical Oncology, Marshfield Clinic Cancer Center, Marshfield, WI, USA, metaresearch@hotmail.com, evaluated relevant literature, using meta-analysis, to determine whether there was convincing evidence for a link between high dietary intake of beta-carotene and lowered risk of epithelial ovarian cancer.
Methods:Literature searches were undertaken to identify relevant studies conforming to predetermined inclusion criteria. Statistical procedures used included a general variance-based meta-analysis. The main outcome measure was the calculation of a summary relative risk (RR) that reflected the risk of ovarian cancer in relation to high versus low dietary beta-carotene intake.
Results:Data from five observational studies involving a total of 3,782 subjects, which showed a lack of statistical heterogeneity, were pooled for meta-analysis. The results revealed a statistically significant summary RR of 0.84, indicating that high (compared with low) dietary beta-carotene intake is associated with a 16% decrease in risk of ovarian cancer. The researchers performed sensitivity analyses on the data, which confirmed that study design differences and differences in quantitative measures of beta-carotene across studies did not affect the calculated summary RR.
Conclusion: High dietary intake of beta-carotene appears to contribute a modest degree of protection against the development of ovarian cancer. Further studies are needed to identify what factors might influence beta-carotene’s effects in the body.
Huncharek M et al. Dietary beta-carotene intake and the risk of epithelial ovarian cancer: a meta-analysis of 3,782 subjects from five observational studies. In Vivo 15 (4): 339-43. Jul-Aug 2001.

MOLASSIOTIS, Department of Nursing, Chinese University of Hong Kong, Hong Kong, China, alexmo@cuhk.edu.hk, assessed the effectiveness of progressive muscle relaxation training (PMRT) for controlling chemotherapy-related nausea and vomiting in women with breast cancer.
Methods: 8 women with breast cancer who were receiving chemotherapy with doxorubicin and cyclophosphamide were given standard oral anti-emetic medication (Maxolon). Half of the patients were randomly assigned to also receive PMRT. A trained nurse guided these patients through a PMRT session once a day for 5 days. Both groups of patients received anti-emetic medication intravenously 30 minutes before they took their chemotherapy drugs. Nausea and vomiting were assessed on the Morrow Nausea and Vomiting Scale.
Results:Statistically, differences between the two groups of patients were borderline, but there were trends towards a shorter duration and a lower intensity of both nausea and vomiting in the group that also received PMRT. Both groups of patients experienced delayed nausea and vomiting due to their [anti-nausea and anti-vomiting] treatments.
Conclusion:Although this was a small study, the results suggested that PMRT may be useful, when given in addition to standard anti-emetic medication, in helping to decrease nausea and vomiting associated with chemotherapy. PMRT is low cost and easy to learn and therefore can easily be incorporated into the care protocols for patients undergoing chemotherapy.
Molassiotis A. A pilot study of the use of progressive muscle relaxation training in the management of post-chemotherapy nausea and vomiting. European Journal of Cancer Care 9 (4): 230-4. Dec 2000.

CAMPBELL and colleagues, Peter McCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia, reviewed (37 references) literature on the therapeutic benefits, safety and nurses’ use of aromatherapy in cancer patient care.
Discussion: Aromatherapy, along with other complementary/alternative medical (CAM) therapies, is being used increasingly in cancer patient care settings. Hence there is a timely need for guidelines to be developed for it safe and appropriate use in clinical practice. The authors of this review undertook to develop a policy for guidance in the clinic. The resulting policy was developed with foremost consideration being given to the needs of the cancer patient. The authors outline standard dosages of essential oils and methods for administering aromatherapy, with safety as the primary consideration.
Campbell L et al. The development of clinical practice guidelines for the use of aromatherapy in a cancer setting. The Australian Journal of Holistic Nursing 8 (1): 14-22. Apr 2001.

GECSEDI, Albany Memorial and Samaritan Hospitals, Members of Northeast Health, in Albany, New York, USA, reviewed (19 references) the role of oncology nurses, as presently pertains to the United States, in providing an important link between oncology physicians, cancer patients and licensed massage therapists (LMTs) with specialist training in providing massage therapy to cancer patients.
Background: Cancer sufferers often seek massage therapy as a means of relaxation, promotion of wellbeing and to help counter unpleasant side effects of their cancer treatment. It is important, however, that they choose a massage therapist who is appropriately trained in the treatment of cancer patients, and, in the United States, who is state licensed. In order to administer safe and effective massage therapy, LMTs require information about the particulars of the patient’s diagnosis, any co-morbid illnesses or conditions, the treatment they are receiving and the patient’s response to that treatment.
Discussion:The oncology nurse can be an important link between the physician prescribing or approving massage therapy and the LMT, and/or between the patient seeking or being prescribed massage therapy and the LMT. Oncology nurses can help educate patients about massage therapy and therapists, stressing the importance of using a massage therapist who has graduated from an accredited programme, meets state licensure requirements and has had specialist training in the treatment of cancer patients. Oncology nurses can also be a conduit for information to the LMT – conveying vital background information about the patient and about any special considerations, for example, the presence of neutropenia or thrombocytopenia. It is important that patients and healthcare providers (physicians, nurses and therapists) collaborate effectively to ensure that cancer patients receive massage therapy that is safe and effective.
Gecsedi RA. Massage therapy for patients with cancer. Clinical Journal of Oncology Nursing 6 (1): 52-4. Jan-Feb 2002.

Issue 77

SCHEMPP and colleagues, Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany, schempp@haut.ukl.uni-freiburg.de, uncovered a hitherto unreported activity – inhibition of tumour cell growth – by hyperforin, a natural antibiotic derived from St. John’s wort.
Methods: The researchers analysed the effects of hyperforin in a range of human and rat tumour cell lines in vivo and in vitro. Measures included IC50 values (concentrations required to inhibit tumour cell growth by 50%) and indicators of apoptosis (programmed cell death) such as the generation of apoptotic oligonucleosomes, typical DNA-laddering, increases in specific enzyme activities (caspase-9 and caspase-3) and apoptosis-specific morphological changes (e.g. damage to mitochondria).
Results: Hyperforin inhibited human and rat tumour cell growth, with IC50 values of 3-15 µM. Hyperforin caused dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and structural changes characteristic of apoptosis in tumour cells. In a breast cancer cell line (MT-450), hyperforin increased the activities of the enzymes caspase-9 and caspase-3; the caspase inhibitor zVAD.fmk inhibited the hyperforin-mediated apoptosis. In MT-450 cells, hyperforin also caused damage to mitochondria. By contrast, the cytotoxic drug paclitaxol did not induce loss of Deltapsi(m) or other indicators of mitochondrial damage. Hyperforin was also able to cause the release of cytochrome C from isolated mitochondria. Treating MT-450 cells with the caspase inhibitor zVAD.fmk did not prevent hyperforin-induced mitochondrial membrane permeabilization. These findings indicated that the mitochondrial permeabilization was a cause rather than the result of caspase activation. When hyperforin and paclitaxol were compared in vivo, they both inhibited the growth of MT-450 cells in rats to a similar extent; hyperforin showed no signs of acute toxicity.
Conclusion: Hyperforin is capable of significantly inhibiting tumour cell growth via activation of a mitochondria-mediated apoptosis pathway. Hyperforin also showed low toxicity in vivo. Taken together with the natural abundance of this agent, the findings indicate hyperforin to be a promising anticancer agent that deserves further study.
Schempp CM et al. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John’s wort that acts by induction of apoptosis. Oncogene 21 (8): 1242-50. Feb 2002.
Comment: These results need to be followed up.

MAILLARD and colleagues, Laboratoire de Biologie des Tumeurs, Clinique d’Oncologie-Radiotherapie, Service de Gynecologie-Obstetrique, E.A. 2103, Unite de Recherche Associee Universite-INRA, CHU, Tours, France, investigated the question of whether n-3 fatty acids protect against the development of breast cancer.
Background: Experimental evidence exists to suggest that n-3 fatty acids such as alpha-linolenic acid (ALA; 18:3, n-3) and long-chain n-3 polyunsaturated fatty acids (PUFAs) can inhibit the growth of breast cancer tumours and their spread to other body areas. Epidemiological studies have investigated the possibility that dietary n-3 PUFAs may protect against the development of breast cancer, but the results of these early studies were inconclusive. The authors of the present report conducted a clinical study to evaluate this question.
Methods: Subjects were 241 patients with invasive non-metastatic breast cancer, and 88 patients with benign breast lumps who acted as controls. The investigators analysed the levels of fatty acids in adipose tissue, taken to be an indicator of the patients’ past dietary consumption levels of fatty acids. Samples of adipose tissue were taken at the time of breast surgery. Individual fatty acid levels, expressed as a percentage of total fatty acids, were measured. Odds ratio estimates of breast cancer risk were calculated using unconditional logistic regression modelling. Data were adjusted for possible confounding factors such as age, height, menopausal status and body mass index.
Results: Breast cancer risk was found to be inversely linked with levels of n-3 fatty acid levels in breast adipose tissue. Women with levels of ALA in the upper third of the range of levels in the whole group had an odds ratio (OR) of 0.39 for breast cancer risk in comparison with those in the lower third. Those with levels of docosahexaenoic acid (DHA; 22:6, n-3) in the highest tertile had an OR of 0.31 compared with those in the lowest tertile. Women with a ratio of long-chain n-3 to total n-6 fatty acids in the highest tertile had an OR of 0.33 compared with those in the lowest tertile.
Conclusion: The results suggest that n-3 fatty acids are protective against breast cancer and lend credence to the view that the ratio of n-3 to n-6 fatty acids is important in the development of breast cancer.
Maillard V et al. N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France. International Journal of Cancer 98 (1): 78-83. Mar 2002.
Comment: A potentially highly significant result!

Issue 76

MONTGOMERY and colleagues, Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029-6574, USA, guy.montgomery@mssm.edu, assessed the effects of brief hypnosis in the period prior to surgery on women undergoing breast biopsies to confirm or refute the diagnosis of breast cancer.
Background: Many thousands of women per year undergo breast biopsies to investigate the possibility of breast cancer, suffering the pain of the procedure and distress due to the threat of cancer. Hypnosis has been shown to be effective in controlling pain associated with other types of surgery, but there has been little study of its effect in breast surgery. The present study examined the effect of brief surgical hypnosis on postsurgical pain and distress in women undergoing breast surgery and explored possible mechanisms mediating the effects of hypnosis.
Methods: 20 women undergoing excisional breast biopsy were randomly assigned to receive presurgical hypnosis or standard care (control group).
Results: Women who underwent presurgical hypnosis experienced less postsurgical pain and distress. Initial findings indicate that the beneficial effects of hypnosis were mediated by the women’s presurgical expectations.
Montgomery GH et al. Brief presurgery hypnosis reduces distress and pain in excisional breast biopsy patients. The International Journal of Clinical and Experimental Hypnosis 50 (1): 17-32. Jan 2002.

GWYN and SINICROPE, Department of Gastrointestinal Medicine and Nutrition, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA, reviewed (91 references) literature on the effectiveness of chemoprevention (using natural or synthetic agents) as a strategy for preventing the development and/or progression of colorectal cancer.
Background: In the USA, colorectal cancer is the third most frequent form of cancer and is the second most common (behind lung cancer) cause of deaths due to cancer. The development of colorectal cancer is characterized by progressive histopathological and molecular genetic changes, a process that offers a multitude of stages in tumourigenesis at which preventive strategies can be targeted.
Discussion: Synthetic or natural chemopreventive agents previously or currently being studied for their potential to prevent the development or progression of colorectal cancer include: non-steroidal anti- inflammatory drugs (NSAIDs), ascorbic acid, calcium compounds, dietary fibre, dietary supplements, folic acid, vitamin E and beta-carotene. Long-term intake of NSAIDs, mainly aspirin, has been shown consistently to reduce the incidence of colorectal adenomas and carcinomas in humans. Cyclo-oxygenase-2 inhibitors, a newer selective class of NSAIDs, have also been shown to be effective in animal models of colorectal cancer. Placebo-controlled studies in humans have shown the NSAID sulindac and the selective cyclo-oxygenase inhibitor Celebrex to be effective chemopreventives in familial adenomatous polyposis; the latter drug has been approved by the FDA for adjunctive treatment in these patients. A variety of chemopreventive agents are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcomes of these studies may have important implications for future management of the disease.
Conclusions: Chemopreventive agents must be effective, safe, well tolerated and relatively cost effective. At present they cannot be recommended for average-risk individuals or those with sporadic colorectal neoplasia. Chemoprevention is still in its infancy, but developments are advancing rapidly. In the future, chemopreventive strategies may trigger important changes in our approach to colorectal cancer.
Gwyn K, Sinicrope FA. Chemoprevention of colorectal cancer. The American Journal of Gastroenterology 97 (1): 13-21. Jan 2002.

VOLKOTRUB and ANDROPOVA [no affiliation provided] reviewed (57 references) international literature, including Russian, on the biological effects of selenium.
Discussion: Data collected from biogeochemical provinces rich in selenium have revealed the significant toxic and carcinogenetic potentials of the element. However, it is known that selenium is essential in trace amounts for human health, and that a low-selenium diet has unfavourable effects in humans. Therapeutic doses of selenium have considerable antioxidative and anticarcinogenic effects. Several medicinal plants have been identified that selectively accumulate selenium from the soil, including some that are concentrators of selenium, showing high biological accumulation coefficients. Recent studies suggest that there is a severe deficiency of selenium in the foods and in the general environment of virtually all of the countries comprising the former USSR. Clinical findings and research studies suggest that selenium-containing drugs, medicinal plant products and selenium-supplemented foods should be strongly recommended in selenium-deficient geographical areas.
Volkotrub LP, Andropova TV. (Role of selenium in the etiology and prevention of diseases (review).) Gigiena i Sanitariia (3): 57-61. May-Jun 2001.
Comment: How tragic that selenium supplements will be severely restricted by the EU Supplement Directive.

Issue 75

MAGILL, Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York University, New York, USA, examined the benefits of music therapy techniques for helping to relieve the suffering and experience of pain in patients with advanced cancer.
Discussion: The experience of pain in patients with advanced cancer is affected by physiological, psychological, social and spiritual factors. Patients are less able to cope with pain (i.e. ‘suffer’) when it is associated with impending loss, increased dependency and a changed perception of their life’s purpose. Comprehensive pain management is aimed at improving comfort, peace of mind and quality of life. Music therapy can offer a range of benefits to patients suffering with pain due to advanced cancer. To design comprehensive treatment programmes, music therapists review patients’ social, cultural and medical history, their current medical status, and how emotions are affecting pain. Therapeutic techniques used may include vocal, listening and instrumental approaches. The various techniques of music therapy enable therapists and patients to explore feelings and issues that compound the patient’s experience of pain. This article presents case examples demonstrating ‘lifting’, ‘transporting’ and ‘bringing of peace’ qualities of music, which can offer patients moments of release, reflection and renewal.
Magill L. The use of music therapy to address the suffering in advanced cancer pain. Journal of Palliative Care 17 (3): 167-72. Autumn 2001.

ZHU and colleagues, Tianjin Institute Hospital, Tianjin 300060, China studied the effects of beta-carotene (BC) on the growth of mammary tumour cells (MA737) in mice.
Methods: TA II mice were fed 250 mg/kg BC (dissolved in vegetable oil) once every 2 days, with or without concomitant chemotherapy (CT). Control mice were fed the vegetable oil vehicle minus BC.
Results: BC-only treatment retarded tumour growth; the effect, however, was greater in those mice receiving BC plus CT (growth inhibition rates: 49.1% versus 60.5%). The effect of BC plus CT on tumour growth was only slightly better than that of CT alone. However, BC helped to reduce toxic side effects of CT, resulting in significantly greater survival times in mice receiving BC plus CT. Long-term treatment with BC did not cause any adverse effects.
Conclusion: In this model of mammary cancer, BC inhibited tumour growth, prolonged survival and reduced the toxic side effects of CT.
Zhu Y et al. Effect of beta-carotene on mouse transplantable mammary cancer MA737. Chung-Hua chung Liu Tsa Chih (Zhonghua Zhong Liu Za Zhi) 21 (4): 262-4. Jul 1999.

PRAKASH and colleagues, Department of Food Science and Nutrition, University of Rhode Island, Kingston, RI 02881, USA, pprakash-mail@yahoo.com, examined, in vitro, the effect of beta-carotene (BC) on the morphology of small cell lung cancer cells (NCI-H69) that had undergone significant (p<0.05) BC-induced growth reduction.
Methods: Cells were grown at a density of 108 cells/L and cultured in the presence or absence of BC (20 mol/L). Morphology was examined using qualitative electron microscopy and quantitative image analysis.
Results: BC-treated cells contained more vacuoles than non-BC-treated cells and showed a significantly smaller nuclear roundness factor value; this indicated that BC-treated cells had an irregular nuclear morphology. BC-treated cells had a significantly smaller major cell diameter and minor nuclear diameter and a significantly larger nuclear perimeter. BC cells also had a significantly lower ratio of nucleus to cytoplasm, indicating less malignant growth.
Conclusion: BC treatment of small cell lung cancer cells caused cell morphological changes along with a reduction in cell proliferation. Further studies are needed to confirm a direct effect of BC or its intracellular polar metabolites on the cell morphology.
Prakash P et al. Beta-carotene alters the morphology of NCI-H69 small cell lung cancer cells. The Journal of Nutrition 132 (1): 121-4. Jan 2002.

LAGIOU and colleagues, Department of Nutrition and Biochemistry, National School of Public Health, Athens, Greece, investigated possible age-dependent effects of diet on the risks of development and progression of prostate cancer.
Background: The authors believed it more likely to be able to identify nutritional factors affecting the risk of developing prostate cancer in younger patients, whereas such factors that might affect progression of the disease would be more apparent in older patients.
Methods: Components of the [reported habitual] diets of 320 patients with prostate cancer and 246 controls (with no systemic disease), hospitalized in 6 major hospitals in Athens, Greece, were analysed. Separate logistic regression models were fitted for men under 70 years of age and men of 70 years or older.
Results: Polyunsaturated fats substantially increased the risk of developing prostate cancer in younger subjects, but had a minimal role in the progression of the disease in older subjects. Cooked tomatoes were strongly protective in older subjects, but not in younger ones. Vitamin E strongly protected against prostate cancer for younger subjects, but not against progression for older subjects.
Conclusion: The results show at the very least that older men with prostate cancer have a different dietary risk profile compared with younger men; such findings have potentially useful implications.
Lagiou A et al. Are there age-dependent effect of diet on prostate cancer risk? Sozial- und Praeventivmedizin 46 (5): 329-34. 2001.
Comment: The above research studies analyzing nutritional components upon cancer growth, morphology and progression is confirmation of the diversity of ongoing research internationally.

Issue 74

BROWN and colleagues, University of Buffalo, State University of New York, Buffalo, NY, USA, provide guidelines, based on available evidence, on optimal nutritional choices for cancer patients and survivors.
Discussion: There have been many studies of dietary interventions for preventing cancer. Guidelines on diet, nutrition and cancer prevention, published by the American Cancer Society, are updated as new evidence emerges. Other groups have also issued statements or guidelines on nutritional strategies for preventing cancer. There is little information, however, concerning optimal nutrition for cancer survivors. This report summarises the available evidence on optimal nutrition choices at different stages of cancer survival and reviews popular complementary and alternative methods that use dietary intervention. Nutritional information relevant to common cancer sites is also given. The article also includes a section on ‘frequently asked questions’, which can be used as a patient education handout, to aid effective communication between cancer survivors and healthcare providers.
Brown J et al. Nutrition during and after cancer treatment: a guide for informed choices by cancer survivors. A Cancer Journal for Clinicians 51 (3): 153-87. May-Jun 2001.
Comment: See book review of Living Proof, page 5 this issue.

JACOBSON and CHETTY, Department of Epidemiology, PH18-105, Mailman School of Public Health and Herbert Irving Cancer Center, Columbia University, 600 West 168th Street, New York, NY 10032, USA, aja4@columbia.edu, reviewed (37 references) the use and possible usefulness of complementary and alternative medicine (CAM) in patients with prostate cancer.
Background: Patients with prostate cancer, similar to other cancer patients and the general populace, are increasingly interested in trying out complementary and alternative medicine (CAM).
Discussion: Some herbal medicines and micronutrients demonstrate biological activities that may be beneficial in the treatment of prostate cancer. Further studies are needed to investigate CAM therapies in the sphere of prostate cancer with respect to their clinical effectiveness, side effects and possible interactions with conventional treatments.
Jacobson JS, Chetty AP. Complementary and alternative medicine in prostate cancer. Current Oncology Reports 3 (5): 448-52. Sep 2001.

GALLAGHER and colleagues, The Harry R. Horvitz Center for Palliative Medicine, Cleveland Clinic, Taussig Cancer Center, Ohio 44195, USA, described a music therapy programme that has recently become established as a standard part of care in palliative medicine at the Cleveland Clinic.
Background: The music therapy programme was developed as a result of a partnership between The Cleveland Clinic Foundation and The Cleveland Music School Settlement.
Discussion: The music therapy programme has had a number of [positive] effects on patients, their families and staff. The authors present a service delivery model for implementation and integration of music therapy within palliative medicine and outline specific music therapy interventions and evaluation and documentation techniques. This article also describes patient and family responses to music therapy, staff satisfaction and effectiveness of interventions.
Gallagher LM et al. Music therapy in palliative medicine. Supportive Care in Cancer 9 (3): 156-61. May 2001.

ATALAH and colleagues, Departamento de Nutricion, Facultad de Medicina, Universidad de Chile, Casilla 13.898, Correo 21, Santiago, Chile, eatalah@machi.med.uchile.cl, investigated possible associations between cervical cancer risk and diet, smoking and sexual behaviour.
Background: Data from epidemiological studies suggest that smoking, nutrition and sexual behaviour are important risk factors for developing cervical cancer.
Methods: The study involved 170 women with cervical cancer and 340 matched controls. Subjects completed a food frequency questionnaire covering 58 food items rich in antioxidants, from which median daily intakes of vegetables, fruit, antioxidant vitamins and fibre were calculated. The researchers calculated odds ratios (ORs) associated with variations in nutritional intake and non-nutritional factors (age at first delivery, parity, body mass index, family history of cancer and smoking).
Results: High consumption of vegetables, fruit, beta-carotene, vitamins C and E and fibre was associated with a lower risk of cervical cancer (OR range 0.56-0.78). Younger age at first delivery, higher total number of pregnancies and smoking were associated with a higher risk of cancer. ORs were: for vegetable and vitamin E consumptions, 0.6; for smoking, 2.8; and for younger age at first delivery, 3.37.
Conclusion: Risk of cervical cancer is related to reproductive behaviours and nutritional factors. High intakes of vegetables and vitamin E-rich foods are associated with reduced risk.
Atalah E et al. (Diet, smoking and reproductive history as a risk factor for cervical cancer.) Revista Medica de Chile 129 (6): 597-603. Jun 2001.

NEWCOMER and colleagues, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA, examined the possible relationship between omega-6 and omega-3 fatty acids and prostate cancer.
Background: Results from studies in animals suggest that omega-6 fatty acids encourage tumour development and omega-3 fatty acids inhibit it. Methods: Subjects were 67 patients newly diagnosed with prostate cancer and 156 controls. The researchers took blood samples from all subjects and measured levels of omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes.
Results: Prostate cancer risk was higher in subjects with the highest RBC levels of alpha-linolenic acid compared with those with the lowest levels (odds ratio [OR] 2.6). A similar association was found for linoleic acid levels (OR 2.1) and total omega-6 fatty acids (OR 2.3).
Conclusion: The findings confirm those of other studies demonstrating associations between linoleic and total omega-6 fatty acids and increased risk of prostate cancer. However, in contrast with findings from animal studies, alpha-linolenic acid was also associated with increased prostate cancer risk. Further clinical studies are needed to clarify the relationship between omega-6 fatty acids and risk of prostate cancer in humans.
Newcomer LM et al. The association of fatty acids with prostate cancer risk. The Prostate 47 (4): 262-8. Jun 2001.

Issue 73

CRAMER and colleagues, Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA, dcramer@partners.org, estimated the consumption of antioxidant vitamins and carotenoids in women with ovarian cancer.
Background: An inverse association between ovarian cancer risk, carotenoids and antioxidant vitamins has been suggested by several epidemiological studies and one experimental trial of a vitamin A analogue.
Methods: From a population-based study of 549 cases of ovarian cancer and 516 controls, the authors estimated the consumption of the antioxidant vitamins A, C, D and E and various carotenoids, including alpha- and beta-carotene and lycopene, using a validated dietary questionnaire. They used multivariate logistic regression to calculate the exposure odds ratios adjusted for established ovarian cancer risk factors.
Results: Intakes of carotene, especially alpha-carotene, from food and supplements were significantly and inversely associated with risk for ovarian cancer, predominantly in postmenopausal women. Food items most strongly related to decreased risk were raw carrots and tomato sauce.
Conclusions: Consumption of fruits, vegetables and food items high in carotene and lycopene may reduce the risk of ovarian cancer.
Cramer DW et al. Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. International Journal of Cancer 94 (1): 128-34. Oct 2001.

MAOKA and colleagues, Research Institute for Production Development, 15 Shimogamo-Morimoto-cho, Sakyo-ku, 606-0805, Kyoto, Japan, maoka@mbox.kyoto-inet.or.jp, analysed anticarcinogenic activities of carotenoids isolated from the red pepper Capsicum annuum L.
Results: Capsanthin and related carotenoids isolated from the fruits of red paprika Capsicum annuum L. showed potent in vitro antitumour-promoting activity, with inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among them, capsanthin diester and capsorbin diester showed strong inhibitory effects. Furthermore, capsanthin, capsanthin 3’-ester and capsanthin 3,3’-diester, major carotenoids in paprika, exhibited potent antitumour-promoting activity in an in vivo mouse skin two-stage carcinogenesis assay using 7,12-dimethylbenz(a)anthracene as an inhibitor and TPA as a promoter.
Maoka T et al. Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L. Cancer Letters 172 (2): 103-9. Oct 2001.

FINLEY and DAVIS, United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, ND 58202, USA, jfinley@gfhnrc.ars.usda.gov, investigated the ability of foods high in selenium (Se) to reduce the incidence of chemically induced colon cancer in a rat model.
Methods: Foods examined were high-Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high-Se wheat product (made by milling high-Se wheat purchased from a seleniferous area). The rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the study, the rats were injected with a chemical carcinogen. After 11 weeks on the diets, colons were examined for preneoplastic lesions (aberrant crypts foci, ACF).
Results: ACF were significantly reduced in rats fed supra-nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra-nutritional amounts of Se from high-Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine (the predominant chemical form of Se in wheat) did not significantly reduce AC.
Conclusions: The findings emphasize the need to study Se in food forms and not extrapolate from previous cancer inhibition studies using pure chemical forms. They also demonstrate that foods high in Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.
Finley JW, Davis CD. Selenium (Se) from high-selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis. BioFactors 14 (1-4): 191-6. 2001.

Comment: The above research regarding the bioavailability of various forms of selenium and their ability to reduce cancer incidence is extremely timely and important. This type of nutritional research is vital in humans for a wide variety of illnesses, as so much is made of various diets and foods which are supposed to and assumed to protect against cancer, heart disease and other conditions. Although some readers might find distasteful the prospect of eating enriched (engineered) cancer-preventing nutrients foodstuffs, I think that if such foods were to be universally available and reasonably cheap, that this might start to counteract damage from the toxic chemical residues polluting most of our food today, which is where I believe the cancer epidemic originates.

GHOSE and colleagues, CRC Beatson Laboratories, The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK, reviewed (35 references) research on the possible mechanism(s) of selenium’s chemopreventive effects.
Background: Accumulated evidence from prospective studies, intervention trials and studies on animal models of cancer has suggested a strong inverse correlation between selenium (Se) intake and cancer incidence. Several putative mechanisms have been suggested to mediate the chemopreventive activities of Se. Of these, the inhibition of cellular proliferation and the induction of apoptosis are particularly attractive.
Discussion: The mitogen-activated protein kinase (MAPK) pathways are known to be important regulators of cell death, and our recent work has focused on the involvement of these pathways in Se -induced apoptosis in primary cultures of oral cancers and corresponding normal mucosa derived from biopsy material. Using this system, the oral carcinoma cells were found to have enhanced sensitivity to apoptosis when treated with certain Se compounds compared with normal oral mucosa. Induction of Fas ligand was associated with Se-induced apoptosis. Signal transduction studies suggest that Se induces several changes in the MAPK signalling pathways, but functional intervention/inhibitor studies indicate that activation of the Jun-terminal kinase (JNK) pathway seems to be most important.
Ghose A et al. Selenium and signal transduction: roads to cell death and anti-tumour activity. BioFactors 14 (1-4): 127-33. 2001.

COMBS and colleagues, Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA, gfc2@cornell.edu, reviewed (35 references) literature pertaining to the mechanism(s) by which selenium (Se) supplementation may prevent cancer, in order to try to identify what levels of selenium (Se) supplementation and possible target plasma Se or Se metabolite levels may be most relevant.
Discussion: The nutritional functions of Se are recognized as being due to a number of Se-containing proteins. It is not clear, however, whether any of these function in the antitumourigenic effects of Se, most of which have been demonstrated for Se exposures greater than those required for selenoprotein expression. Indeed, other antitumourigenic mechanisms have been demonstrated for certain Se metabolites. The Nutrition Prevention of Cancer Trial found supplemental Se (200 g/day as Se-enriched yeast) to be associated with significant reductions in cancer risks in subjects with pretreatment plasma Se concentrations below ca. 120 ng/ml (1.5 nmoles/ml), which level would appear to require food Se intakes of ca. 1.5 g/kg body weight/day. However, the putative anticarcinogenic Se metabolite(s) should be more relevant than total plasma Se as a supplementation target for cancer prevention. These may be components of the non-protein-bound fraction of Se in plasma, which constitutes 2-4% of total plasma Se.
Combs GF Jr et al. An analysis of cancer prevention by selenium. BioFactors 14 (1-4): 153-9. 2001.

ZAGRODZKI and colleagues, Department of Food Chemistry and Nutrition, Collegium Medicum Jagiellonian University, Krakow, Poland, zagrodzk@alf.ifj.edu.pl, undertook a study to clarify whether the activities of selenoenzymes can serve as markers for different tumours or goitres, as classified by histological criteria.
Methods: The researchers determined: 1) selenium content of plasma (Se); 2) activities of the selenoenzymes plasma glutathione peroxidase (plGSHPx), cytosolic glutathione peroxidase (cGSHPx), type I and type II iodothyronine deiodinases (ID-I, ID-II) and thioredoxin reductase (THRR) in human thyroid tissues.
Results: No significant differences were found in Se or in p1GSHPx between patients and healthy volunteers. No significant differences were found for any parameter in thyroid carcinoma versus normal or goitrous thyroid tissue. In the whole group of thyroid surgery specimens, statistically significant correlations were found between ID-I and ID-II and between THRR and selenoperoxidases. Principal components analysis confirmed these correlations and also revealed correlation between Se and p1GSHPx, but did not detect any clear distinction between patients with the different diagnoses.
Zagrodzki P et al. Selenoproteins in human thyroid tissues. BioFactors 14 (1-4): 223-7. 2001.

KIREMIDJIAN-SCHUMACHER and ROY, Division of Biological Sciences, Medicine and Surgery, New York University College of Dentistry, New York, NY 10010, USA, lk2@nyu.edu, reviewed (30 references) evidence that Se supplementation enhances immune responsiveness during conventional treatment of tumours and the possible additional role of immunotherapy with interleukin-2 (IL-2) in preventing tumour recurrence.
Discussion: In patients undergoing therapy for squamous cell carcinoma (SQCC) of the head and neck (e.g. surgery, radiation, or surgery and radiation), supplementation with 200 g/day of sodium selenite resulted in significantly enhanced cell-mediated immune responsiveness, which was evident during and following conclusion of therapy. Control patients who received placebo supplements showed a decline in immune responsiveness during therapy. Results from studies in mice inoculated with SQCC cells expressing the receptor for IL-2 and supplemented with Se (2.00 ppm) indicated that Se significantly retards the clinical appearance of tumours: peritumoural injections of 2,000 IU of IL-2 resulted in 50% reduction in the size of established tumours and 72% of early tumours. The combined data suggested that local immunotherapy with IL-2 in hosts supplemented with Se may represent an effective modality of treatment for the prevention of recurrences at the site of conventionally treated primary tumours.
Kiremidjian-Schumacher L, Roy M. Effect of selenium on the immunocompetence of patients with head and neck cancer and on adoptive immunotherapy of early and established lesions. BioFactors 14 (1-4): 161-8. 2001.

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