ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Migration studies suggest that the high incidence of postmenopausal breast cancer in Western women is related mainly to epigenetic factors. Progression from ductal carcinomain situ(DCIS) to invasive ductal carcinoma (IDC) also appears to involve environmental rather than genetic factors, and a role has been postulated for metabolic-endocrine changes related to the Western lifestyle. Protein kinase C (PKC) is important in cell signal transduction, and laboratory studies show that PKC stimulates the activities of urokinase plasminogen activator, matrix metalloproteinases and cell adhesion molecules, all of which are known to increase invasiveness in human mammary cancer cell lines. In rodents, the activity of PKC in tissue cells is enhanced by insulin, and PKC isoenzymes have been shown to stimulate the development of hyperinsulinaemic insulin resistance in rodents. Clinically, hyperinsulinaemia and the concomitant increase in circulating levels of free oestradiol and bioactive insulin-like growth factor 1 (IGF1) are each confirmed markers of high risk for breast cancer in women. Lesions of DCIS show evidence of regression with mammary involution, but it is postulated that this may be opposed by the concomitants of hyperinsulinaemic insulin resistance. The prevalence of the latter is increasing in Western populations, and a combination of high IGF1 and low IGF-binding protein 3 concentrations has been associated with the presence of DCIS lesions in premenopausal women. Measures that enhance insulin sensitivity in such women may reduce the risk of progression in DCIS lesions, and a clinical trial is proposed to test the hypothesis.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We investigated the association of p53 abnormalities (gene mutations by DNA sequencing and protein over-expression by immunostaining) with clinical data and prognosis in 74 patients with resected non-small cell lung cancer (NSCLC). DNA analysis of exons 5–8 of the p53 gene showed 34 mutations in 74 resected primary NSCLC (45.9%). Immunohistochemical study of the p53 protein revealed that 41 of 74 (55.4%) samples had positive staining. We found strong agreement between the results of the p53 protein expression test (p53-PE) and the p53 gene mutation test (p53-M) (Cohen's kappa = 0.65, 95% CI 0.48–0.82). Joint distribution of the results (analysed using the bivariate Dale model) was mainly influenced by histological type of tumour. A positive result for the p53-PE test significantly increased (estimated odds ratio 84.5; 95% CI 8.89–803.03) the odds of observing a positive result in the p53-M test. In the univariate analysis (log rank test), positive results in the p53-M test and the p53-PE test were significantly associated with overall survivalP< 0.001 andP= 0.005, respectively). In the multivariate analysis (Cox's proportional hazard model), a positive result for the p53-M test significantly increased relative risk for overall survival (RR 9.56; 95% CI 2.62–34.87;P< 0.001). When the result of the p53-M test was accounted for, a positive result for the p53-PE test did not offer any additional prognostic information due to the strong dependence of results of the tests. However, when the result of the p53-M test was removed from the model, a positive result for the p53-PE test became a significant unfavourable prognostic factor (P= 0.009). We conclude that p53 gene mutation and protein expression analyses are in a strong agreement. Joint distribution of the results depends mainly on histological type of tumour. When considered separately, both tests are unfavourable prognostic factors in NSCLC. When the result of the p53-M test is taken into account, the p53-PE test does not offer any additional prognostic information.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

A prospective case-control study was conducted in Trivandrum, India, to evaluate the dietary risk factors for stomach cancer. One hundred and ninety-four patients with stomach cancer registered at the Regional Cancer Centre (RCC), Trivandrum, Kerala, India, during the period 1988–1991 were considered as cases. A minimum of one control (n= 305), matched for age (±5 years), sex, religion and residential area was selected from the visitors to RCC during the same period. Interviews were carried out using a predetermined structured food frequency questionnaire. The information collected also included socio-demographic/ economic background, tobacco chewing, tobacco smoking and alcohol habits. Data were analysed using a multiple logistic regression model. Odds ratios for all dietary variables were estimated. Increased risks were observed with higher consumption of rice (OR 3.9; 95% CI 1.6–10.0). Risk was high for those consuming spicy food (OR 23; 95% CI 1.1–5.0), high consumption of chilli (OR 7.4; 95% CI 4.0–13.5) and consumption of high-temperature food (OR 7.0; 95% CI 3.7–12.9). On multivariate analysis, high consumption of rice, high consumption of chilli and consumption of high-temperature food were found to be independent risk factors.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Colorectal cancer is the leading cancer in non-smokers in Western countries, and over the last decades its trends have been generally more favourable for women than for men. Possible explanations of the sex differentials in colorectal cancer relate to different exposure to exogenous hormones and to other risk factors including diet, physical activity and alcohol drinking. The objective of this investigation was to systematically analyse the trends in colorectal cancer mortality sex ratios in major European countries over the last four decades. Trends in death certification rates from colorectal cancer over the period 1955–1996 were analysed for 20 European countries (excluding the former Soviet Union and a few of the smaller countries). In all countries, the mortality sex ratios (M/F) were around or slightly above unity in the 1950s, and systematically increased to approach 1.5 in the 1990s. The extent of the rises varied across countries, ranging between + 0.8% in Germany, + 9.7% in Sweden, and + 12.1% in Denmark (the lowest increases) to + 653% in Spain, + 56.2% in Portugal, and + 50.4% in Hungary (the highest ones). Mortality sex ratios in Europe show more favourable trends for females, which may be attributable, in part, to the introduction of exogenous hormones in the late 1950s and 1960s, and, in part, to differential sex exposure to major environmental risk factors.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We examined whether the harmful influence of nulliparity on breast cancer risk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps synergistically on breast cancer risk. Our study population consisted of 129 cases and 517 controls who had been participants in the Nijmegen breast cancer screening programme for 10 years. Breast density was classified with a fully automated technique on digitized mammograms from the screening examination 10 years before diagnosis. Classification was based on the proportion of the breast that was composed of high density: < 5%, 5–25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, administered at the same examination. We found that nulliparae with low breast density (< 5%) were not at increased risk compared to parous women with low density: OR 1.1 (95% CI 0.2–5.8). Parous women with < 5% density formed the reference category throughout all analyses. The risks for parous women with 5–25% or > 25% density were 2.7 (95% CI 1.3–5.6) and 3.6 (95% CI 1.7–7.7) fold increased, respectively. However, when both factors were present (nulliparityand> 5% density), breast cancer risk was 7.1 times higher (95% CI 3.2–15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro-glandular tissue with increased epithelial cell proliferation) is more susceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Since there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have important implications for the prevention and early detection of breast cancer.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In 1998, Storey and co-workers suggested that individuals homozygous for arginine (Arg) at codon 72 of the p53 gene are about seven times more susceptible to human papillomavirus (HPV)-related carcinogenesis than heterozygotes. Since then, several studies from Northern Europe, Japan and the USA have failed to demonstrate a similar correlation. By contrast, a study in Brazil as well as one recent study in Italian and Swedish populations showed strong positive associations. We examined the frequency of p53 codon 72 polymorphism in samples from both invasive and intra-epithelial cervical neoplasias (CIN), and compared them with samples from healthy controls. All 88 samples came from women with a Greek ethnic background. Tissue specimens were collected from archival material with histologically diagnosed low-grade CIN (LGCIN), high-grade CIN (HGCIN) or cervical cancer (CxCa). As a control, we used cellular material newly collected by cytobrush from the cervices of 30 healthy women with normal cytological and colposcopical examinations. p53 Arg homozygosity (Arg/Arg) alone was associated with four-, six- or eight-fold increased risks for LGCIN, HGCIN or invasive cancer, respectively. The frequency of the p53Arg/Arg genotype and of the proline (Pro) allele showed significant linear trends according to the degree of severity of the lesion (P= 0.0007 andP= 0.0009, respectively). Exclusion of the ten HPV16/18-negative cases did not substantially alter the Arg/Arg frequency among the groups nor the significant linear trend. Our results confirm the initial findings of Storey and co-workers, as well as the data of the Brazilian and the recent European study, but do not accord with those of the other aforementioned studies. Variations in ethnic background, laboratory performance, verification of the HPV status, definition of controls, aud sample size are the most plausible explanations for this controversy. In all our samples, the distribution of the p53 alleles fits the Hardy-Weinberg equilibrium and the 0.48 frequency of the Pro allele in our controls accords well with the percentages previously reported for different ethnic groups as characteristic of the assumed north-south dine. Some authors assert that the discrepancy in the results could not be attributed to differences in the methods; however, the Brazilian study emphasized the effect of inter-laboratory variation in detecting the association between p53 polymorphism and cervical cancer. Regarding the control group, our samples were only from women with a cytologically and colposcopically benign cervical epithelium. We think that simply choosing ‘normal volunteers' for collecting control DNA blood samples without knowing the status of their cervical epithelium is indeed a possible source of bias. Finally, it is very unlikely that loss of heterozygosity at the p53 locus could be a factor interfering with the allelotype distribution. Our present small study results, which suggest a biologically relevant association, provide strong evidence that homozygous arginine at codon 72 of p53 may confer a higher susceptibility to HPV-associated intra-epithelial and invasive cervical neoplasia.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Diet appears to be a major determinant in the incidence of prostate cancer. In a case-control study conducted in Athens, Greece, we found that dairy products, butter and seed oils were positively associated with risk of prostate cancer, whereas cooked and raw tomatoes were inversely associated. We utilized the data from this study to calculate the population attributable fractions under alternative assumptions of feasible dietary changes. For each subject, a dietary score was calculated and categorized into approximately quintiles, representing increasing levels of prostate cancer risk as a function of the intake of the five discriminatory food groups or items. Population attributable fractions in terms of this dietary score were calculated taking into account multivariate adjustment. We observed that, if all individuals were shifted to the baseline category, the incidence of prostate cancer in this study population would be reduced by 41% (95% confidence interval 23–59%). However, if all individuals were shifted to the adjacent lower risk quintile, the expected incidence reduction would be a more modest 19%. The incidence of prostate cancer in Greece could be reduced by about two-fifths if the population increased the consumption of tomatoes and reduced the intake of dairy products, and substituted olive oil for other added lipids.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Using participants in the 1970–1972 Nutrition Canada Survey (NCS), a retrospective cohort study was conducted to assess the relationship between tea, as well as coffee, cola and alcohol, and the risk of developing prostate cancer. The mortality and cancer experience of male NCS participants aged 50–84 years was determined up to 31 December 1993. Among the 3400 survey participants included in the study, 145 developed prostate cancer. No association was observed between tea (predominantly black tea) intake and prostate cancer. Subjects who drank more than 500 ml of tea per day experienced virtually the same risk as those who reported no tea consumption (rate ratio (RR) 1.02, 95% confidence interval (CI) 0.62–1.65). Compared to those who reported no coffee drinking, men who averaged more than 250 ml per day experienced a 40% increase in risk (95% CI 0.84–2.32). Cola consumption was not associated with an increased risk of prostate cancer. Total alcohol consumption was not related to subsequent development of prostate cancer, although very moderate consumption of wine (< 10 g per day), relative to no consumption, showed an RR of 1.48 (95% CI 1.05–2.09). These data do not support an association between consumption of tea and prostate cancer risk.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Cotton swab anal smear instead of stool occult blood test can not only be used as a mass screening method for colorectal cancer, but is an auxiliary way to screen hepatobiliary pancreatic carcinoma. Two hundred and twenty-three cases of hepatobiliary pancreatic carcinoma patients received anal occult blood test, of which 121 were positive (54.3%). The screening test was performed in 14645 healthy people aged 40–60 years; 511 persons (3.4%) were positive for anal blood. Among these, six cases of digestive tract cancer were found (one oesophageal carcinoma, one gastric cardia carcinoma, two gastric carcinomas, two liver carcinomas). This suggests that when anal occult blood is positive, the patient should be scanned by ultrasonic means to rule out hepatobiliary pancreatic tumour.

ISSN:0959-8278    

出版商:OVID    

年代:2000

数据来源: OVID