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The objectives of the UICC declared at the outset were of an essential nature for preventive oncology and have very slowly been carried forward. Activities have rapidly expanded with progress in medicine and biology. Strengthening of the International cooperative network since 1980 has accelerated this trend. Most of the initial aims of the Union have now been achieved, I believe, but there appear many further problems to be resolved in cancer prevention, not only in economically developed areas but also in developing regions. Obtaining finance continues to be a big task with regard to accomplishing the many objectives of the UICC. Personal donations from individuals joining the Roll of Honor have provided part support for many projects, but the efforts of the Finance Committee, in coordination with member organizations, are still keys to maintaining activities and reaching the final goal of effective cancer control.
The International Agency for Research on Cancer (IARC) convened a working Group of experts in March 1999 to evaluate the cancer preventive potential of nine retinoids and to compile the fourth volume of the IARC Handbooks of Cancer Prevention. The handbook provides a comprehensive review of the relevant information in the published scientific literature through March 1999 on the potential role of all-trans-retinoic acid, 13-cis-retinoic acid, 9-cisretinoic acid, all-trans N-(4-hydroxyphenyl)retinamide, etretinate, acitretin, N-ethylretinamide, targretin and LGD 1550 in cancer prevention. Of these, the data suggest that all-trans-retinoic acid, 13-cis-retinoic acid and Nethylretinamide are not suitable for chemoprevention of cancer in humans either because they are too toxic, may enhance cancer occurrence or are ineffective. In contrast, 9-cis-retinoic acid, etretinate and acitretin show some promise, but more data are required, while all- trans N-(4-hydroxyphenyl)retinamide is quite promising. Targretin and LGD 1550 are of interest, based on theoretical grounds, but there are no significant human and little experimental data as yet.
The protective role of two commonly consumed natural dietary items- bitter gourd and tomato against endogenous as well as 7,12- dimethylbenz(a)anthracene (DMBA) induced lipid peroxidation in the livers of mice was investigated. The rationale for such an approach is that lipid peroxidation has been suggested to play a key role in human cancer development. There was a sharp rise in lipid peroxidation (measured as thiobarbituric acid reactive substances formation) during skin carcinogenesis induced by DMBA in mice. Aqueous extracts of bitter gourd and tomato juice were found to be very potent inhibitors of lipid peroxidation both in normal and DMBA treated mice. Our observations support the hypothesis that natural combinations of phytochemicals present in the fruit juices exert cancer-protective effects via a decrease in lipid peroxidation.
The human dry dock, a Japanese system of detailed health check-ups for middle-aged and elderly people was originally set up for the purpose of secondary prevention, but it is now expected to increasingly play a role in primary prevention. A series of our studies of smoking cessation in the human dry dock setting showed that the abstinence rate increased from 5-6% for non-advised smokers to 9-10% for those who were advised. Thoracic CT screening participants were found to be more likely to quit smoking. It can be estimated that an additional seventy thousand male smokers would quit smoking every year if advice on smoking cessation was routinely given in every dock in Japan.
The dietary effect of monoglucosyl-rutin (M-R), a flavonoid, on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with 5 week old, F344 male rats. In the first experiment (5 weeks study), effects of MR on AOM (15 mg/kg body weight 3 times weekly)-induced formation of aberrant crypt foci (ACF) in five groups were assessed. In this experiment, group 3 given 500 ppm M-R with AOM had a significantly smaller number of ACF containing 4 or more aberrant crypts than group 1 with AOM alone, and groups 2 and 3 given 100 ppm or 500 ppm M-R respectively had significantly lower BrdU labeling indices in the epithelial cells of large bowel than group 1. For the second experiment, rats were divided into 8 groups. Groups 1-5 were given AOM as in the first experiment. Groups 2-5 were fed diets containing 100ppm or 500ppm M-R for 4 weeks in the initiation phase or 36 weeks in the post-initiation phase. Group 6 was given 500ppm M-R throughout the experiment, and group 7 was kept on the basal diet and served as a control. At the termination of the experiment (40 weeks after the start), groups 2-5 had significantly smaller numbers of positive cells with anti-proliferating cell nuclea antigen (PCNA) antibody than group 1. Furthermore, group 5 treated with 500ppm M-R for 36 weeks demonstrated tendencies for decrease in the incidence and multiplicity of colon tumors. These data suggest that M-R has the potential to inhibit AOMinduced colon carcinogenesis.
Purpose The short-term effects of intravesical chemoimmunotherapy with epirubicin and Bacillus Calmette- Guerin (BCG) administered repeatedlly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 22 patients with a median of 70 years between March, 1995 and February, 1999, and were compared with those of BCG monotherapy in 50 patients between March, 1995 and February, 1999. Patients and Methods The patients underwent intravesical instillation of Tokyo-strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1❛2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were instilled into the bladder by turn once a week for 12 weeks. For the BCG alone group, 80 mg instillation were performed with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. Results and Conclusions The simple recurrence rate was 22.7% (5/21) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of severe bladder-irritation symptoms due to instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was inferior in comparison with BCG monotherapy for prophylaxis of recurrence of superficial bladder cancer.
Smoking is, and long has been, more prevalent among Maori than non-Maori in New Zealand. Lung cancer, but not other smoking-related cancers, is known to be markedly more common among Maori than non-Maori. Incidence and mortality data from the New Zealand Cancer Registry for cancers of the mouth/pharynx, oesophagus, pancreas, larynx, kidney and bladder, as well as lung/pleura, during the period 1974 to 1993 were analysed by sex to determine whether the rates of each of these smoking-related cancers were higher in Maori than in non-Maori. Truncated (35- 64 yr) age-standardized incidence rates for 1974-93 were significantly higher in Maori than non-Maori for cancers of the pancreas, lung/pleura and kidney (both sexes), mouth/pharynx and oesophagus (males only). There was no difference between the Maori and non-Maori rates for cancer of the larynx, and bladder cancer incidence was significantly lower in Maori than non-Maori. Mortality rates followed a similar pattern as those for incidence for cancers of the pancreas, larynx, lung/pleura and kidney (both sexes) and bladder (males only). The pattern predicted by the higher prevalence of smoking in Maori than non-Maori was borne out for all smoking-related cancers except bladder and laryngeal cancer. Under-enumeration through lower access to health services may have contributed to the lower than expected rates of bladder cancer in Maori, but a role for a genetically or lifestyle related protective effect is suggested.
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A population-based case-control study was carried out to investigate risk factors for hepatocellular carcinoma (HCC) in Nagoya, Japan, including hepatitis virus infections, drinking and smoking habits and genetic polymorphisms in aldehyde dehydrogenase2 (ALDH2) and cytochrome P4502E1 (CYP2E1). A total of 84 patients with HCC and 84 sex, age and residence pair-matched controls were recruited for this study. By univariate analysis, hepatitis B virus (HBV) (OR=5.14; 95%CI=2.29-11.6) and hepatitis C virus (HCV)(OR=32.00; 95%CI=7.83-130.7) infections, having a history of blood transfusion (OR=5.25; 95%CI=1.80-15.29), and habitual smoking (OR=2.36; 95%CI=1.17-4.78) were significantly linked to cases; by multivariate analysis, HCV infection (OR=23.5; 95%CI=5.07-108.9) and habitual smoking (OR=5.41; 95%CI=1.10-26.70) were still associated with a significantly increased risk. The c1/c1 genotype of CYP2E1 (odds ratio [OR]= 0.45; 95% confidence interval [CI]=0.21-0.99), detected by Pstl and Rsal digestion was significantly more prevalent in the control group, while 1-1 genotype of ALDH2 (OR=1.24; 95%CI=0.70-2.20) did not demonstrate variation. There were no statistically significant interactions between habitual smoking/drinking and genetic polymorphisms of ALDH2/P4502E1 with reference to HCC development. These findings suggest that viruses, especially HCV infection, and habitual smoking are major independent risk factors, while genetic polymorphisms of ALDH2 and CYP2E1 have only limited contribution to the risk of HCC in Nagoya, Japan.
If smokers have different lifestyle including dietary habit in comparison to non-smokers, this difference have an influence on the evaluation of the risks of smoking for tobacco-related diseases or the design of anti-smoking campaigns. In Japan, 1,745 men over the age of 40 were surveyed regarding health consciousness in 1996 and 2,136 men between the ages of 50 and 65 were surveyed regarding dietary habits in 1993-1994. Comparative analysis was done among the smoking and non-smoking groups. The rate of participation in cancer mass-screening for smokers was significantly lower than for non-smokers. Smokers had consumed significantly lower amounts of vegetables, fruits and beans, which are well known beneficial factors for health than non-smokers, and had consumed more salt, salty food and alcohol, which are well known risk factors for health. It is suggested that smokers have disadvantageous characteristics for promoting and maintaining a healthy lifestyle more than in non-smokers. Accordingly, to evaluate the risk of smoking for tobacco-related diseases in epidemiological researches, we should properly treat these data as confounding factors. Furthermore, anti-smoking campaigns should be performed considering these differences.
Colorectal cancer is thought to originate in colorectal adenoma and endoscopic polypectomy may prove prophylactic. To clarify the natural history of colorectal adenoma and the potential effects of endoscopic polypectomy, we retrospectively studied cohort patients undergoing full colonoscopies at 14 hospitals in Aomori Prefecture between January 1972 and December 1985. Subjects were divided into 3,574 non-adenoma controls and 1,020 adenoma patients, including 530 treated by polypectomy at initial examination. Subjects were followed up until the end of 1987 through record linkage with Aomori Colorectal Cancer Registry files to observe colorectal cancer occurrence. The ratio of observed number/expected number in the general population (O/E ratio) was 0.70 for the adenoma group and 0.36 for controls. The adenoma group was subdivided into polypectomy and non-polypectomy subgroups, with the O/E ratios of 0.39 for polypectomy patients and 0.75 for non-polypectomy patients. The O/E ratio in the adenoma group was about twice in controls, and this ratio in the nonpolypectomy subgroup was also about twice in thepolypectomy subgroup. Tha results suggest that colorectal adenoma provides a precancerous lesion that can be treated prophylactically by endoscopic polypectomy.
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