Cancer In High-risk Population Research Articles

Skin cancer chemoprevention: strategies to save our skin.

There are over 1 million cases of skin cancer diagnosed yearly in the United States. The majority of these are nonmelanoma (NMSCs) and are associated with chronic exposure to ultraviolet light (UV). Actinic keratosis (AK) has been identified as a precursor for SCC, but not for BCC. AKs are far more common than SCC, making them excellent targets for chemoprevention. Cancer chemoprevention can prevent or delay the occurrence of cancer in high-risk populations using dietary or chemical interventions. We have developed strategies that have rational mechanisms of action and demonstrate activity in preclinical models of skin cancer. Promising agents proceed to phase I-III trials in subjects at high risk of skin cancer. UV light induces molecular signaling pathways and results in specific genetic alterations (i.e., mutation of p53) that are likely critical to skin cancer development. UVB-induced changes serve as a basis for the development of novel agents. Targets include inhibition of polyamine or prostaglandin synthesis, specific retinoid receptors, and components of the Ras and MAP kinase signaling pathways. Agents under study include: epigallocatechin gallate (EGCG), a green tea catechin with antioxidant and sunscreen activity, as well as UVB signal transduction blocking activity; perillyl alcohol, a monoterpene derived from citrus peel that inhibits Ras farnesylation; difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase and polyamines; retinoids that target retinoid X receptors and AP-1 activity; and nonsteroidal anti-inflammatory agents that inhibit cylooxygenase and prostaglandin synthesis. We performed a series of Phase I-II trials in subjects with multiple AK. For example, a phase II randomized trial of topical DFMO reduced AK number, suppressed polyamines, and reduced p53 protein. Our goal is to develop agents for use in combination and/or incorporation into sunscreens to improve chemoprevention efficacy and reduce skin cancer incidence.

Oral preneoplasia and chemoprevention of squamous cell carcinoma of the head and neck.

ConclusionsMicronutrients and phytochemicals modulate genetic pathways of carcinogenesis and inhibit the initiation and progression of SCCHN. These compounds may have a role in the prevention of cancer in high-risk populations, such as tobacco smokers, as well as in the prevention of disease progression or relapse. Clinical studies investigating the use of these agents in the prevention ofSCCHN should be a high priority.

Clinical experience with upper extremity venous sonography in a high-risk cancer population.

To determine the frequency of sonographically evident upper extremity venous thrombosis in symptomatic cancer patients with and without central venous catheters. Retrospective review of 573 consecutive upper extremity venous sonographic reports from a 26-month period was performed. Findings including distribution of venous thrombosis, the presence of a central line, cancer type, and miscellaneous findings were recorded. Overall, 514 studies (90%) had satisfactory visualization of all upper extremity vessels; 53 (9%) had limited visualization of 1 or more vessels; and 6 (1%) were inconclusive. Venous thrombosis was present in 227 (40%) of 573 studies. Of the studies with positive findings, there were 186 acute, 13 chronic, 19 fibrin sheath versus nonocclusive, and 9 superficial thromboses. Central venous catheters were present in 325 (57%) of 573 studies. Sonographically evident thrombosis was present in 157 (48%) of 325 studies with central catheters versus 70 (28%) of 248 studies without central venous catheters (P = .001) Upper extremity venous thrombosis is common (40%) in symptomatic cancer patients and is nearly twice as frequent in cancer patients with indwelling central venous catheters.

Randomized Controlled Community Trial of the Efficacy of a Multicomponent Stage-Matched Intervention to Increase Sun Protection among Beachgoers

Background. Skin cancer is about as common as all other cancers combined and is preventable by sun protection. The most intense sun exposures often occur on the beach, so we chose this setting to test an intervention to affect sun protection behaviors. Methods. We developed a multicomponent stage-matched intervention for beachgoers and evaluated its efficacy in a randomized trial for influencing stage of change and self-reported behavior. Results. We randomized 2,324 persons ages 16 to 65 on the beach (83% of those approached). The intervention was effective in increasing self-reported sun protective behaviors. Effects were similar across gender and age groups. Conclusions. The beach is a good site for recruitment and intervention to prevent skin cancer in high-risk populations. Our stage-matched intervention package was effective for increasing sun protective behaviors.

Screening for Prostate Cancer in High Risk Populations

Screening for Prostate Cancer in High Risk Populations

Screening for Prostate Cancer in High Risk Populations

Black men and men with a family history of prostate cancer are at higher risk for this disease and may have an earlier age of onset. Consequently, screening at a younger age has been recommended for high risk men, however, there are limited data on actual screening results in young, high risk populations. In men 50 years old or older we compared screening results in 1,224 black men, 1,227 men with a positive family history and 63 men who were both with those of 15,964 nonblack men with no known family history. In high risk men in their forties we also evaluated the percent with abnormal screening tests, the positive predictive value of screening tests, cancer detection rates and the prognostic features of tumors detected. In men 50 years old or older prostate cancer detection rates were 6.4% for controls compared with 10.3%, 10.5% and 17.5%, respectively, for the high risk groups. Among high risk men screened in their forties 8% had suspicious screening tests and approximately 55% who underwent a biopsy had cancer detected. Of tumors detected 80% were organ confined and all but 1 were of moderate Gleason grade 5 years old or older. Only 1 tumor (7%) fulfilled the published criteria for a possibly harmless cancer. Black men and men with a family history of prostate cancer are at a 75% to 80% higher risk for prostate cancer. On initial screening of high risk men in their fourth decade only 8% have positive screening tests; however, approximately 55% of these men have tumors, most of which are medically important with favorable prognostic features.

Lower extremity venous sonography in the high-risk cancer population: one leg or two?

We correlated the diagnostic yield of unilateral and bilateral lower extremity venous sonograms in a high-risk cancer population with the clinical indication for the examination. Reports from 433 bilateral and 619 unilateral lower extremity Doppler sonograms obtained over an 18-month period in patients with cancer were retrospectively reviewed, and clinical indication and findings were determined. Overall, 228 (22%) of 1052 examinations revealed deep venous thrombosis (DVT): 83 (19%) of 433 bilateral and 145 (23%) of 619 unilateral. Among studies performed for unilateral symptoms (pain, edema, or postorthopedic procedure), 23% (135/581) of unilateral and 27% (44/162) of bilateral studies revealed DVT. Among these 44 bilateral studies with positive findings performed for unilateral symptoms, there were 30 DVT in the symptomatic side, 12 bilaterally, and two in the asymptomatic side alone. Ten percent (11/110) of the bilateral studies performed for bilateral symmetric symptoms revealed DVT. Among studies performed for bilateral asymmetric symptoms, 13% (1/8) of the unilateral and 8% (2/25) of the bilateral studies revealed DVT; both bilateral studies showed positive findings in the more symptomatic side. Among studies performed for suspected or proven pulmonary embolus, 20% (23/113) of bilateral and 54% (7/13) of unilateral studies had positive findings. In a high-risk cancer population, the incidence of DVT in patients with unilateral symptoms is more than twice that of patients with bilateral symptoms. Because DVT isolated to an asymptomatic lower extremity is rare (1%), bilateral sonographic examination is generally unnecessary with unilateral lower extremity symptoms.

Sex-related differences in bronchial epithelial changes associated with tobacco smoking.

Lung cancer is the most common cause of cancer death in North American women. Because smoking-related changes in the bronchial epithelium and in lung function have not been studied in detail in women, we used fluorescence bronchoscopy-directed biopsy to determine the prevalence of high-grade preinvasive lesions in former and current smokers of both sexes. Spirometry, white-light bronchoscopy, and fluorescence bronchoscopy were performed in 189 women and 212 men older than 40 years of age who had smoked 20 pack-years or more (pack-years = number of packs of cigarettes smoked per day x number of years of smoking). Carcinoma in situ was found in 1.8% of the subjects, severe dysplasia was found in 6.5%, and moderate dysplasia was found in 14% (all preinvasive lesions). Compared with men, women had a lower prevalence of high-grade preinvasive lesions in the observed airways (14% versus 31%; odds ratio = 0.18; 95% confidence interval = 0.04-0.88), and women with preinvasive lesions had fewer such lesions (two-sided P = .048). The prevalence of preinvasive lesions did not change substantially for more than 10 years after cessation of smoking. Lung function was associated with the prevalence of preinvasive lesions, but the association was weaker in women than in men. If the presence of airflow obstruction was defined by an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) value of 70% or less, only 56% of the men and 44% of the women with preinvasive lesions had abnormal lung function. In developing strategies for chemoprevention or early detection of lung cancer in high-risk populations, it is important to consider the effect of sex and arbitrarily chosen lung function values on the prevalence of preinvasive airway lesions.

Cancer prevention

Cancer prevention

Moving promising research findings to the clinic: Methodological issues in the design and conduct of clinical trials of retinoids

International Journal of CancerVolume 70, Issue 4 p. 467-469 Special ReportFree Access Moving promising research findings to the clinic: Methodological issues in the design and conduct of clinical trials of retinoids Andrew Arnold, Corresponding Author Andrew Arnold Department of Medical Oncology, Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre and McMaster University, Hamilton, CanadaDepartment of Medical Oncology, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada, Fax (905) 575-6316Search for more papers by this author Andrew Arnold, Corresponding Author Andrew Arnold Department of Medical Oncology, Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre and McMaster University, Hamilton, CanadaDepartment of Medical Oncology, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada, Fax (905) 575-6316Search for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1097-0215(19970207)70:4<467::AID-IJC15>3.0.CO;2-CCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Arnold, A. M., Browman, G. P., Levine, M. N., D'Souza, T., Johnstone, B., Skingley, P., Turner-Smith, L., Cayco, R., Booker, L., Newhouse, M. and Hryniuk, W. M., The effect of the synthetic retinoid etretinate on sputum cytology-results from a randomized trial. Brit. J. Cancer, 65, 737– 743 (1992). Arnold, A., Kowaleski, B., Tozer, R. and Hirte, H., The arotinoids: early clinical experience and discussion of future development. Leukemia, 11, 1817– 1824 (1994). Eisenhauer, E. A., Lippman, S. M., Kavanagh, J. J., Paredes-Espinoza, M., Arnold, A., Hong, W. K., Massimini, G., Schleuniger, U., Bollag, W., Holdener, E. and Krakoff, I., Combination 13-cis-retinoic acid and interferon α2a in the therapy of solid tumours. Leukemia, 10, 1622– 1625 (1994). Eliason, J. F., Kaufmann, F., Tanaka, T. and Tsukaguchi, T., Anti-proliferative effects of the arotinoid Ro 40–8757 on human cancer cell lines in vitro. Brit. J. Cancer, 67, 1293– 1298 (1993). Goodman, G. E., Metch, B. J. and Omenn, G. S., The effect of long-term beta-carotene and vitamin A administration on serum concentrations of alpha-tocopherol. Cancer Epidemiol. Biomarkers Prev., 3, 429– 432 (1994). Hennekens, C., Buring, J., Manson, J., Stampfer, M., Rosner, B., Cook, N., Belanger, C., LaMotte, R., Gaziano, J., Ridker, P., Willett, W. and Peto, R., Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. New Engl. J. Med., 334, 1145– 1149 (1996). Kelly, K., Evaluation of k-ras mutations in sputum samples by single stranded conformation polymorphism [Abstract]. Lung Cancer, 11 (Suppl.), 225 (1994). Lee, J. S., Lippman, S. M., Benner, S. E., Lee, J. J., Ro, J. Y., Leukeman, J. M., Morice, R. C., Peters, E. J., Pang, A. C., Fritsche, H. A. and Hong, W. K., Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia. J. clin. Oncol., 12, 937– 945 (1994). Mathé, G., Gouveia, J. and Hercend, T., Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment. Cancer Detect. Prevent., 5, 461– 466 (1982). Omenn, G., Goodman, G., Thornquist, M., Balmes, J., Cullen, M., Glass, A., Keogh, J., Meyskens, F., Valanis, B., Williams, J., Barnhart, S. and Hammar, S., Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. New Engl. J. Med., 334, 1150– 1155 (1996). Omenn, G. S., Goodman, G., Thornquist, M., Grizzle, J., Rosenstock, L., Barnhart, S., Balmes, J., Cherniack, M. G., Cullen, M. R. and Glass, A., The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res., 54 (Suppl.), 2038s– 2043s (1994). Citing Literature Volume70, Issue47 February 1997Pages 467-469 ReferencesRelatedInformation

Successful screening for early esophageal cancer in alcoholics using endoscopy and mucosa iodine staining.

Epidemiologic studies have provided evidence that alcohol abuse is an important risk factor for esophageal carcinoma. However, no systematic screening program has been established yet in the early detection of esophageal cancer in high risk populations of heavy drinkers. A cohort of 629 male alcoholics (54 +/- 8 years old) were consecutively and systematically screened by endoscopy combined with iodine staining and targeted biopsy at the National Institute on Alcoholism (Kanagawa, Japan). For mucosal carcinomas, endoscopic esophageal mucosal resection (EEMR) was used to serve confirmatory diagnostic and therapeutic purposes. Iodine-unstained lesions, distinctly demarcated, white, and 5 mm or larger in greatest dimension, were observed on the esophageal wall in 162 patients (25.8%). Thirty-six such unstained lesions in 21 of 629 patients, with an unexpectedly high rate of 3.3%, turned out to be squamous cell carcinomas of the superficial type. According to some established criteria, EEMR was performed in 17 of these patients, 3 of whom were given additional irradiation. Esophagectomy was performed in two patients, chemotherapy combined with irradiation in one, whereas still another was followed endoscopically. The cancer invasion was confined within the epithelium in eight patients, to the proper mucosal layer in nine, and to the submucosa in four. Multiple logistic regression revealed that the risks for distinct iodine-unstained lesions and superficial esophageal carcinoma increased independently for users of stronger alcoholic beverages, i.e., whiskey or shochu (odds ratio [OR] = 1.47 and 2.94, respectively) compared with lighter beverages, i.e., sake or beer and 30+ cigarettes/day (OR = 1.68 and 3.85, respectively). Routine application of this program for these high risk individuals yielded an unusually high rate of detection of esophageal carcinoma.

The β-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: Smokers and asbestos-exposed workers : Omenn GS, Goodman G, Thornquist M, Grizzle J, Rosenstock L, Barnhart S et al. CARET Coordinating Center, Fred Hutchinson Cancer Research Ctr., Seattle, WA 98104. Cancer Res 1994; 54:Suppl 2038s-43s

The β-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: Smokers and asbestos-exposed workers : Omenn GS, Goodman G, Thornquist M, Grizzle J, Rosenstock L, Barnhart S et al. CARET Coordinating Center, Fred Hutchinson Cancer Research Ctr., Seattle, WA 98104. Cancer Res 1994; 54:Suppl 2038s-43s

Diagnostic significance of measurement of fecal bile acids in colorectal cancer patients

Fecal bile acid values in 23 patients with colorectal cancer were shown to have diagnostic significance. Deoxycholic acid (DCA) and cholic acid (CA) were measured using the enzyme-linked immunosorbent assay method and the DCA:CA ratio was used for the pre- and postoperative comparison. The postoperative ratio was found to be lower than the preoperative ratio in every patient. This finding indicates the clinical usefulness of the DCA:CA ratio in monitoring the progress of colorectal cancer. This type of monitoring may be useful for screening patients for colorectal cancer in high-risk populations.

CARET, the beta-carotene and retinal efficacy trial to prevent lung cancer in high-risk populations : Omenn GS. Fred Hutchinson Cancer Research Ct., Seattle, WA 98195. Public Health Rev 1991;1992;19:205–8

CARET, the beta-carotene and retinal efficacy trial to prevent lung cancer in high-risk populations : Omenn GS. Fred Hutchinson Cancer Research Ct., Seattle, WA 98195. Public Health Rev 1991;1992;19:205–8

Experience from clinical trials in cancer prevention.

Conduct of randomized, controlled, large-scale prevention trials is fundamental to the full assessment of the efficacy of interventions to prevent cancer. Clinical trials in cancer prevention, which include dietary modification and chemoprevention, are based on leads from epidemiological and laboratory studies. Dietary intervention trials involve the modification of overall eating patterns, whereas chemoprevention trials involve the administration of natural or synthetic substances reported to have anticarcinogenic properties, e.g. vitamins, minerals, and pharmaceuticals. Clinical/metabolic studies can help advance knowledge of the role of diet in the etiology and prevention of cancer by investigating the metabolism of factors thought to influence cancer risk; thus, these studies have the potential to provide a stronger scientific base for progression to randomized, controlled clinical trials. Cancer prevention trials supported by the National Cancer Institute include the Polyp Prevention Trial, which is testing a low-fat, high-fibre, and vegetable- and fruit-enriched eating pattern on the prevention of polyp recurrence, and the Nutrition Intervention Trials of Oesophageal Cancer in Linxian, China, which are testing the efficacy of vitamin-mineral supplements in the prevention of oesophageal cancer in high-risk populations. Results from clinical cancer prevention trials will enable investigators to establish more firmly the relationships between diet and cancer and to translate the information effectively into significant reductions in cancer incidence and mortality.

Genetic predisposition to cancer

Genetic predisposition to cancer - an introduction from families to chromosomes - genetic linkage and other methods of finding cancer-predisposing genes how to isolate cancer-predisposing genes retinoblastoma - the paradigm for a genetically inherited cancer syndrome neurofibromatosis - types I and II multiple endocrine neoplasia - types I and II Wilms' tumor and other genetic causes of renal cancer the Li-Fraumeni syndrome and cancers arising from germline p53 mutations ataxia telangiectasia and radiation sensitivity Fanconi's anemia Gorlin's syndrome xeroderma pigmentosum and related syndrome genetics and the common cancers familial breast cancer the breast/ovarian cancer syndrome and BrCA1 screening for breast cancer in high-risk populations. The management of women with a high risk of breast cancer: (1) prophylactic tamoxifen (2) the contraversy of prophylactic mastectomy. familial prostrate cancer and its management psychological effects of the high-risk breast cancer the genetics of familial colon cancer familial melanoma and its management the organization of a familial cancer clinic screening for known cancer-predisposition genes the ethics of testing for cancer predisposition genes.

A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China

The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.

CARET, the β-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers

CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.

Precursor lesions of esophageal cancer in high-risk populations in Henan Province, China.

This report discusses precancerous changes in the esophageal mucosa from three points of view: the histopathologic features of the esophageal mucosa in persons known to be at high risk for esophageal carcinoma (EC); the histopathologic features of the esophageal mucosa of asymptomatic persons randomly selected from areas at high and low risk for EC; and a prospective follow-up of a randomly examined group to determine the impact of esophagitis and dysplasia upon subsequent development of EC. Esophagitis was commonly found at endoscopic examination, but there was no difference in frequency of esophagitis in the randomly selected subjects from high-risk and low-risk areas. Although one third of patients with dysplasia developed cancer over a follow-up period of 30 to 78 months, only 4% of those with esophagitis alone developed EC. The authors conclude that dysplasia, diagnosed by cytologic or histologic examination, is a precancerous state, and that esophagitis is a nonspecific pathologic condition of the esophagus, but moderate and severe types of chronic esophagitis might create an environment favorable for the development of esophageal carcinoma.

A suction-abrasive cytology tube for the diagnosis of esophageal carcinoma.

A simple, easily constructed, and inexpensive suction-abrasive cytology tube was developed to study esophageal cytology. The reliability of this method for the diagnosis of esophageal carcinoma was evaluated in 101 patients. Of 47 patients with esophageal carcinoma, 93% were diagnosed correctly on exfoliative cytology. There were no false diagnoses of cancer. The cytology tube was well tolerated by all patients and provided a rapid and reliable method of diagnosis. As a screening procedure, this method may be applicable for widespread use to detect early esophageal cancer in high-risk populations.