石棉及电焊烟尘相关肺癌组织K-ras基因突变的研究

为了解石棉及电焊烟尘相关肺癌的Ｋ－ｒａｓ基因突变情况,并与非职业肺癌的Ｋｒａｓ基因突变特点比较,进一步探讨石棉及电焊烟尘的致癌机理。收集８例非职业肺癌组织、９例石棉相关肺癌组织及４例电焊烟片段长度多态性分析,单链构象多态性分析及ＤＮＡ真接测序分析。     

Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies

BACKGROUND: Whereas obesity has been associated with an increased risk of colon cancer in men, a weak or no association has been observed in women. Results for rectal cancer have also been inconsistent. OBJECTIVE: The objective was to perform a meta-analysis to summarize the available evidence from prospective studies on the associations of overall and abdominal obesity with the risk of colon and rectal cancer. DESIGN: We searched MEDLINE (1966-April 2007) and the references of the retrieved articles. Study-specific relative risks (RRs) were pooled by using a random-effects model. RESULTS: Thirty prospective studies were included in the meta-analysis of body mass index (BMI; in kg/m(2)). Overall, a 5-unit increase in BMI was related to an increased risk of colon cancer in both men (RR: 1.30; 95% CI: 1.25, 1.35) and women (RR: 1.12; 95% CI: 1.07, 1.18), but the association was stronger in men (P < 0.001). BMI was positively associated with rectal cancer in men (RR: 1.12; 95% CI: 1.09, 1.16) but not in women (RR: 1.03; 95% CI: 0.99, 1.08). The difference in RRs between cancer sites was statistically significant (P < 0.001 in men and P = 0.04 in women). Colon cancer risk increased with increasing waist circumference (per 10-cm increase) in both men (RR: 1.33; 95% CI: 1.19, 1.49) and women (RR: 1.16; 95% CI: 1.09, 1.23) and with increasing waist-hip ratio (per 0.1-unit increase) in both men (RR: 1.43; 95% CI: 1.19, 1.71) and women (RR: 1.20; 95% CI: 1.08, 1.33). CONCLUSIONS: The association between obesity and colon and rectal cancer risk varies by sex and cancer site.     

Food and nutrient intakes and K-ras mutations in exocrine pancreatic cancer

BACKGROUND: No studies have investigated the relation between K-ras mutations and dietary factors in exocrine pancreatic cancer (EPC), and fewer than 10 studies have done so in other neoplasms. Patients and METHODS: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission. Food and nutrient intakes were measured with a food frequency questionnaire. Logistic regression was used to compare EPC cases (n = 107) with and without K-ras mutations (case-case study). RESULTS: K-ras mutations were more common among daily consumers of milk and other dairy products than among non-daily consumers: the odds ratio adjusted by total energy, age, sex, smoking, alcohol and coffee consumption (ORa) was 5.1 (95% CI 1.1 to 24.5, p = 0.040). For all dairy products, including butter, the ORa for the medium and upper tertiles of intake were 5.4 and 11.6, respectively (p for trend = 0.023). The ORa for regular coffee drinkers further adjusted by dairy consumption was 4.7 (95% CI 1.1 to 20.7, p = 0.043). K-ras mutated cases reported a lower intake of vitamin E (ORa = 0.2, p for trend = 0.036), polyunsaturated fats and omega 3 fatty acids (ORa = 0.2; p for trend <0.03). CONCLUSIONS: Results support the hypothesis that in EPC exposure to specific dietary components or contaminants may influence the occurrence or persistence of K-ras mutations.     

Alcohol consumption and cancer risk

This review focuses on selected aspects of the relation between alcohol consumption and cancer risk. Heavy alcohol consumption (i.e., ≥4 drinks/day) is significantly associated with an increased risk of about 5-fold for oral and pharyngeal cancer and esophageal squamous cell carcinoma, 2.5-fold for laryngeal cancer, 50% for colorectal and breast cancers, and 30% for pancreatic cancer. These estimates are based on a large number of epidemiological studies and are generally consistent across strata of several covariates. The evidence suggests that at low doses of alcohol consumption (i.e., ≤1 drink/day) the risk is also increased by about 20% for oral and pharyngeal cancer and 30% for esophageal squamous cell carcinoma. Thus, for these sites there is little evidence of a threshold effect. While consumption of fewer than 3 alcoholic drinks/wk is not associated with an increased risk of breast cancer, an intake of 3 to 6 drinks/wk might already yield a (small) increase in risk. On the other hand, intakes up to 1 drink/day are not associated to the risk of laryngeal, colorectal, and pancreatic cancer. The positive association between alcohol consumption and the risk of head and neck cancers is independent from tobacco exposure.     

Population-attributable risk for colon cancer in Italy.

Risk factors for colon cancer have essentially been considered in terms of relative risks. From a public health viewpoint, however, their impact depends not only on the strength of the association, but also on the distribution of exposures in the population. Thus we used data from a case-control study conducted in Italy between 1992 and 1996 to estimate the population-attributable risks (PARs) for colon cancer in relation to educational level, physical activity, energy and vegetable intake, eating frequency, and family history of colorectal cancer. Cases were 1,225 incident, histologically confirmed colon cancer patients admitted to the major teaching and general hospitals in six Italian areas; controls were 4,154 subjects with no history of cancer, admitted to hospitals in the same catchment areas for acute, nonneoplastic diseases. By use of the distribution of the risk factors in the cases and the multivariate relative risk estimates, PARs were computed, i.e., the proportion of colon cancer that would have been avoided if all subjects were moved to the lowest exposure level. The PARs were 12% for high education, 14% for low physical activity, 14% for high energy intake, 22% for low vegetable intake, 7% for high eating frequency, and 8% for a family history of colorectal cancer. These factors together accounted for 56% of colon cancer cases. PARs were similar across age strata. Men had higher PARs for education, physical activity, and their combination, but lower PARs for energy, eating frequency, vegetable intake, and their combination than women. The percentage of colon cancers attributable to all factors considered together was 50% in men and 67% in women. Even if the PAR estimates were based on several arbitrary assumptions on the exposure distribution for various risk factors, available knowledge could, in principle, explain > 50% of cases in this Italian population, thus indicating and quantifying the theoretical scope for prevention.     

BRCA1 and BRCA2 gene mutations and risk of breast cancer. Public health perspectives.

CONTENT: Breast cancer is the most common cancer and the second most common cause of cancer death among U.S. women. In 1998, about 178,700 new cases will be diagnosed and 43,500 women will die from the disease. Mutations in the BRCA1 gene, which was cloned in 1994 and is located on chromosome 17q, have been identified as causes of predisposition to breast, ovarian, and other cancers. A second breast cancer gene, BRCA2, has been localized to chromosome 13q. Using inferential procedures, the overall carrier frequency of BRCA1 gene mutations has been estimated at 1 in 500 in the general U.S. population. Recent studies have indicated that the carrier frequency of a specific BRCA1 allele, the 185delAG mutation, may be as high as 0.8% to 1% among women of Ashkenazi Jewish descent. CONCLUSIONS: Due to the proliferation of laboratories offering genetic tests for breast cancer susceptibility, their appropriate use in public health needs careful scrutiny. Several issues are raised when such genetic tests are considered for population-based prevention programs for breast cancer. Public health agencies, such as the Centers for Disease Control and Prevention, are important to monitoring and evaluating genetic testing done outside of research protocols. If genetic tests for breast cancer are to be incorporated into future prevention programs, evaluation is needed of whether the testing can have the intended effect.     

肺癌患者K-ras、FHIT基因异常与吸烟关系

目的 探讨吸烟与肺癌患者原癌基因K-ras点突变和人类脆性组氨酸三联体(FHIT)基因转录异常的关系,探讨吸烟致肺癌作用靶点.方法 应用PCR-RFLP和RT-PCR分别检测80例肺癌患者及20例正常肺组织中K-ras、FHIT基因的异常情况,分析吸烟与K-ras、FHIT基因异常的关系.结果 肺癌组织K-ras基因突变率为52.58%,FHIT基因转录异常阳性率为71.25%,与正常肺组织比较差异均有统计学意义(P<0.05).肺癌组吸烟者的K-ras、FHIT基因异常率高于不吸烟者(P<0.05).K-ras、FHIT基因异常与吸烟指数相关联,列联系数P分别为0.337和0.399;吸烟与肺腺癌K-ras基因点突变、肺鳞癌和小细胞肺癌的FHIT基因异常转录关系密切(P<0.05).肺癌患者K-ras突变与FHIT转录异常无明显关联性,但两者在肺癌组织中差异有统计学意义(P<0.01).结论 K-ras、FHIT基因异常与肺癌发生密切相关.吸烟是肺腺癌中K-ras基因点突变和肺鳞癌、小细胞肺癌中FHIF基因异常转录的一个重要因素.     

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group

STUDY OBJECTIVE: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer. DESIGN: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.     

Alcohol consumption and the risk of breast cancer

To examine the relation between alcohol consumption and breast cancer, the authors used data from the Centers for Disease Control's Cancer and Steroid Hormone Study, a multicenter population-based case-control study. Between August 1981 and December 1982, 3,498 US women aged 20-54 years with newly diagnosed breast cancer and 3,157 women aged 20-54 years selected at random from the same geographic areas were asked about their consumption of alcoholic beverages during the previous five years. Women who drank any alcohol had a risk of breast cancer of 1.0 (95% confidence interval 0.9-1.2) compared with nondrinkers. The risk of breast cancer did not increase appreciably with increasing alcohol consumption: Risk estimates for women consuming 8-14, 15-21, and 22 or more drinks per week were 1.1, 1.0, and 1.2, respectively. The authors also found no notable differences by type of beverage or within specific risk factor subgroups. These findings do not support the hypothesis that alcohol consumption increases the risk of breast cancer.     

Alcohol consumption and the risk of gastric cancer

The relationship between alcohol drinking and gastric cancer risk was analyzed using data from a case-control study conducted in Northern Italy between 1985 and 1993 on 746 cases of histologically confirmed incident stomach cancer and 2,053 controls in hospital for acute nonneoplastic nondigestive tract diseases. Wine was the most frequently consumed alcoholic beverage, accounting for approximately 90% of all alcohol consumption. Compared with those who never drank wine, the odds ratios (OR) were 1.1 [95% confidence interval (CI) 0.9-1.3] for fewer than four drinks per day, 1.3 (95% CI 1.0-1.7) for four to fewer than six drinks per day, 1.6 (95% CI 1.1-2.4) for six to fewer than eight drinks per day, and 1.4 (95% CI 1.0-2.0) for eight or more drinks per day. No association was observed with beer or spirits. For total alcohol consumption, 25% of cases and 30% of controls never drank alcohol, and the multivariate OR for those who drank versus those who did not drink was 1.1 (95% CI 0.9-1.4). After allowance for smoking, education, family history of stomach cancer, selected micronutrient intake, and nonalcohol calorie intake, the ORs were 1.1 (95% CI 0.9-1.4) for fewer than six drinks per day, 1.0 (95% CI 0.4-1.4) for six to fewer than eight drinks per day, and 1.3 (95% CI 0.9-1.9) for eight or more drinks per day, and the trend in risk was not significant. No interaction was observed between alcohol drinking and sex, family history, and smoking, but the association with alcohol drinking was appreciably stronger in the elderly and in less-educated individuals. Thus this large data set was able to exclude a strong and consistent association between alcohol (mainly wine) drinking and stomach cancer risk. A nonsignificant association was observed in those who drank very heavily, but the absence of a dose-risk relationship suggests that even such a moderate association may reflect inadequate allowance for covariates or the presence of other risk factors (possibly related to diet and social class) among the heaviest drinkers.     

PPARgamma, energy balance, and associations with colon and rectal cancer

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been hypothesized as being involved in colorectal cancer given its role in adipocyte development and insulin resistance. In this study we evaluated the association between the Pro12Ala (P12A) PPARgamma polymorphism and body mass index (BMI), waist-to-hip ratio (WHR), physical activity level, and energy intake and risk of colorectal cancer using data from a population-based, case-control study of colon cancer (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls). We further evaluated how the P12A PPARgamma polymorphism is associated with obesity and fat pattern in the control population. The odd ratio for PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9 (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0-1.5) adjusting for race, age, and sex. P12A PPARgamma did not significantly interact with BMI, WHR, energy intake, and energy expenditure to alter risk of colon or rectal cancer. Furthermore, the P12A PPARgamma polymorphism was not associated with obesity or WHR in the control population; it did not interact with energy intake or energy expenditure to alter risk of obesity or large WHR. These data do not support the hypothesis that the P12A PPARgamma polymorphism is associated with colon or rectal cancer through regulation of energy balance.     

Alcohol consumption and ovarian cancer risk

To study the influence of alcohol consumption on the risk of ovarian cancer in women under age 55, the authors examined data collected in a multicenter, population-based case-control study--the Centers for Disease Control's Cancer and Steroid Hormone Study. Between August 1981 and December 1982, 433 women 20-54 years of age with newly diagnosed ovarian cancer and 2,915 women 20-54 years of age selected at random from the same geographic areas were asked about their consumption of alcoholic beverages during the previous five years. Women who drank any alcohol during the five-year period had a risk of ovarian cancer of 0.9 (95% confidence interval (CI) = 0.7-1.2) compared with nondrinkers. Risk was not associated with the type of alcoholic beverage consumed, nor were the results affected by controlling for demographic characteristics and oral contraceptive use. Although there was no association between moderate alcohol consumption and ovarian cancer, women who drank more than about 20 drinks per week had a relative risk of ovarian cancer of 0.5 (95% CI = 0.2-0.9) compared with women who did not drink.     

Fried foods and the risk of colon cancer

High-temperature cooking of foods produces a variety of mutagenic substances. Because of the association of such substances with carcinogenesis, the authors used a case-control study of colon cancer conducted in Utah between 1977 and 1979 with 246 cases and 484 controls to test the hypothesis that persons with colon cancer would report more frequent use of fried and broiled meats. Intake of food was measured by a food frequency questionnaire which focused on food use five years before the interview. For men, the odds ratios for the highest level of use were 1.2 (90% confidence interval (CI): 0.8-1.9) for fried meats and 0.7 (90% CI: 0.5-1.0) for broiled meats; for women, the odds ratios were 1.3 (90% CI: 0.8-2.1) for fried meats and 1.1 (90% CI: 0.7-1.7) for broiled meats. The reported use of fried and broiled vegetables was too infrequent to permit evaluation. The authors conclude that the ingestion of fried and broiled meats five years before diagnosis of colon cancer had little influence on the development of this cancer.     

Collinear nutrients and the risk of colon cancer

The relationship between colon cancer risk and the relative contributions of fat and caloric intake are assessed. A lack of consensus exists regarding the role of each of these dietary factors in the development of colon cancer. This lack of agreement originates from the high correlations between the nutrients, as well as the manner in which researchers treat these dietary variables in their analyses. Four proposed methods are evaluated which attempt to address the collinearity problem in nutritional epidemiology: (1) exclude one or more collinear variables, (2) use the proportion of calories consumed attributable to each dietary component, (3) use a regression-adjustment approach to purge the collinearity correlated nutrients, and (4) ridge regression. Diagnostic tests are reported which assess the degree of collinearity on data collected for a case-control study of colon cancer conducted in Utah between 1979 and 1983. Using logistic regression analyses, we apply each of these methods to case-control data. We find that the risks associated with fat and caloric consumption are extremely sensitive to a priori analytic decisions made by epidemiologist about the underlying collinearity problem.     

Eating frequency and the risk of colon cancer

Eating frequency has been found in most previous studies to have a positive association or no association with colon cancer. We report data from a large case-control study to determine the effect of eating frequency on colon cancer risk. Data were analyzed from interviews of 1,966 cases of colon cancer and 2,380 controls from selected areas in Northern California, Utah, and Minnesota. Respondents were asked whether they usually ate or drank something besides water at eight different occasions during the day. We controlled for age, family history of colorectal cancer, body mass index, physical activity, intake of non-steroidal anti-inflammatory medication, and dietary intake of energy, fiber, and calcium. In fully adjusted models, we found no significant associations between number of daily eating occasions and colon cancer in women. In men, risk of overall colon cancer was lower for one to two times per day (odds ratio = 0.54, 95% confidence interval = 0.36-0.83) than for three times per day, but risk was not increased for more than three times per day. Compared with three times per day, we found no evidence for an association between colon cancer risk and eating frequencies more than three times per day. The increased risk of colon cancer limited to men eating less than three times per day may be due to uncontrolled confounding.     

Lifestyle and colon cancer: an assessment of factors associated with risk.

Studies of the etiology of colon cancer indicate that it is strongly associated with diet and lifestyle factors. The authors use data from a population-based study conducted in northern California, Utah, and Minnesota in 1991-1995 to determine lifestyle patterns and their association with colon cancer. Data obtained from 1,993 cases and 2,410 controls were grouped by using factor analyses to describe various aspects of lifestyle patterns. The first five lifestyle patterns for both men and women loaded heavily on dietary variables and were labeled: "Western," "moderation," "calcium/low-fat dairy;" "meat and mutagens," and "nibblers, smoking, and coffee." Other important lifestyle patterns that emerged were labeled "body size," "medication and supplementation," "alcohol," and "physical activity." Among both men and women, the lifestyle characterized by high levels of physical activity was the most marked lifestyle associated with colon cancer (odds ratios = 0.42, 95% confidence interval: 0.32, 0.55 and odds ratio = 0.52, 95% confidence interval: 0.39, 0.69, for men and women, respectively) followed by medication and supplementation (odds ratio = 1.68, 95% confidence interval: 1.29, 2.18 and odds ratio = 1.63, 95% CI 1.23, 2.16, respectively). Other lifestyles that were associated with colon cancer were the Western lifestyle, the lifestyle characterized by large body size, and the one characterized by calcium and low-fat dairy. Different lifestyle patterns appear to have age- and tumor site-specific associations.