Asymmetric synthesis of the chlorocyclopropane-containing callipeltoside A side chain.

[reaction: see text] The callipeltoside A chlorocyclopropyl-containing dienyne side chain has been synthesized in nine steps and 33% overall yield from commercially available 1,2,5,6-O-dicyclohexylidene-D-mannitol. The key steps in the synthesis are a highly diastereoselective cyclopropanation of a vinyl chloride allylic ether and a Suzuki cross-coupling to complete the carbon framework.

Alcohol and other beverage use and prostate cancer risk among Canadian men.

There are very few large scale studies that have examined the association of prostate cancer with alcohol and other beverages. This relationship was examined in a case-control study conducted in 3 geographical areas of Canada [Metropolitan Toronto (Ontario), Montreal (Quebec), and Vancouver (British Columbia)] with 617 incident cases and 637 population controls. Complete history of beverage intake was assessed by a personal interview with reference to a 1-year period prior to diagnosis or interview. In age- and energy-adjusted models for all centers combined, the odds ratio (OR) for the highest quintile of total alcohol intake was 0.89. For alcoholic beverages separately, it was 0.68 for the highest tertile of beer, 1.12 for wine and 0.86 for liquor. The decreasing trend was significant for beer intake. The results were only significant for British Columbia out of all the 3 centers studied. Whereas coffee and cola intake was not associated with prostate cancer, a decrease in risk was observed with tea intake of more than 500 g per day (OR 0.70). Our results do not support a positive association between total alcohol, coffee and prostate cancer.

Nutrition and pancreatic cancer.

Epidemiologic evidence on the relation between nutrition and pancreatic cancer is reviewed. A number of epidemiologic studies of diet and cancer of the pancreas have been reported including descriptive, case-control, and cohort studies. Overall, fairly consistent patterns of positive associations with the intake of meat, carbohydrates, and dietary cholesterol have been observed. Consistent inverse relationships with fruit and vegetable intakes and, in particular, with two markers of such foods, namely fiber and vitamin C, also have been noted. However, the methodologic limitations of these studies, particularly the descriptive and case-control studies, are such that causal inferences regarding these empirical associations currently are not warranted. Future follow-up of existing dietary cohorts should enable more precise assessment of the possible role of diet in the etiology of cancer of the pancreas.

Do the nonsmoking daughters of smokers tend to marry smokers? Implications for epidemiological research on environmental tobacco smoke: the IARC collaborative study.

The IARC collaborative study on exposure to environmental tobacco smoke (ETS) involved collecting interview data and biochemical indicators of exposure from 1369 nonsmoking women in 13 centers in 10 countries. Information on childhood and adulthood exposure to other people's smoke and duration of this exposure from both parents and spouse was gathered at the interview. Of the 900 women whose husbands smoked (current or exsmokers), 71.3% had one or both parents who smoked (predominantly the father), whereas among the 277 women married to never-smokers, only 60.3% had at least one parent who smoked. The odds ratio for the daughter of a smoker to marry a smoker was, therefore, 1.64 (95% confidence interval = 1.24-2.17; P > 0.001), and there was an exposure-response relation between the number of years of childhood exposure to ETS from the parents and the likelihood of being married to a smoker. These results show that nonsmoking women married to smokers are more likely to have been exposed to tobacco pollution during their whole life. Because the duration of exposure is known to be important in the genesis of lung cancer, some of the excess risk of lung cancer in nonsmoking women married to smokers may be due exposure to ETS from parents during childhood.

Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

BACKGROUND: International and interethnic differences in prostate cancer incidence suggest an environmental, potentially modifiable etiology for the disease. PURPOSE: We conducted a population-based case-control study of prostate cancer among blacks (very high risk), whites (high risk), and Asian-Americans (low risk) in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto. Our aim was to evaluate the roles of diet, physical activity patterns, body size, and migration characteristics on risk in these ethnic groups and to assess how much of the interethnic differences in risk might be attributed to interethnic differences in such lifestyle characteristics. METHODS: We used a common protocol and questionnaire to administer personal interviews to 1655 black, white, Chinese-American, and Japanese-American case patients diagnosed during 1987-1991 with histologically confirmed prostate carcinoma and to 1645 population-based control subjects matched to case patients by age, ethnicity, and region of residence. Sera collected from 1127 control subjects were analyzed for levels of prostate-specific antigen (PSA) to permit comparison of case patients with control subjects lacking serological evidence of prostate disease. Odds ratios were estimated using conditional logistic regression. We estimated the proportion of prostate cancer attributable to certain risk factors and the proportion of interethnic risk differences attributable to interethnic differences in risk-factor prevalence. RESULTS: A positive statistically significant association of prostate cancer risk and total fat intake was found for all ethnic groups combined. This association was attributable to energy from saturated fats; after adjusting for saturated fat, risk was associated only weakly with monounsaturated fat and was unrelated to protein, carbohydrate, polyunsaturated fat, and total food energy. Saturated fat intake was associated with higher risks for Asian-Americans than for blacks and whites. In all ethnic groups combined, the risk tended to be higher when only case patients with advanced disease were compared with control subjects with normal PSA levels. Among foreign-born Asian-Americans, risk increased independently with years of residence in North America and with saturated fat intake. Crude estimates suggest that differences in saturated fat intake account for about 10% of black-white differences and about 15% of white-Asian-American differences in prostate cancer incidence. Risk was not consistently associated with intake of any micronutrients, body mass, or physical activity patterns. CONCLUSIONS: These data support a causal role in prostate cancer for saturated fat intake but suggest that other factors are largely responsible for interethnic differences in risk.

Dietary factors and risk of prostate cancer: a case-control study in Ontario, Canada.

The relationship between risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Ontario, Canada. Cases were men with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992. Controls were selected randomly from assessment lists maintained by the Ontario Ministry of Revenue, and were frequency-matched to the cases on age. The study included 207 cases (51.4 percent of those eligible) and 207 controls (39.4 percent of those eligible), and information on dietary intake was collected from them by means of a quantitative diet history. There was a positive association between energy intake and risk of prostate cancer, such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk. In contrast, there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk. There was some evidence for an inverse association with saturated fat intake, although the dose-response pattern was irregular. There was a weak (statistically nonsignificant) positive association between polyunsaturated fat intake and risk of prostate cancer. Relatively high levels of retinol intake were associated with reduced risk, but there was essentially no association between dietary beta-carotene intake and risk. There was no alteration in risk in association with dietary fiber, cholesterol, and vitamins C and E. Although these patterns were evident both overall and within age-strata, and persisted after adjustment for a number of potential confounding factors, they could reflect (in particular) the effect of nonrespondent bias.

Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type.

A case-control study of male-female differences in cigarette smoking and lung cancer was conducted during 1981-1985 in Toronto, St. Catharine's, and Niagara Falls, Ontario, Canada. In total, 442 female and 403 male histologically verified cancer cases were individually matched by age and area of residence to each other and to 410 female and 362 male randomly selected population controls. Subjects were interviewed concerning their exposures to various life-style factors, and in particular, they received detailed questioning regarding their lifelong histories of usage of tobacco products. It was found that, for both sexes, a greatly elevated risk of developing lung cancer was associated with cigarette consumption, increasing with pack-years of cigarettes smoked and declining with duration of time since quitting smoking. Furthermore, the association was significantly (p = 0.010) and appreciably stronger for females than for males. At a history of 40 pack-years relative to lifelong nonsmoking, the odds ratio for women was 27.9 (95% confidence interval (CI) 14.9-52.0) and that for men was 9.60 (95% CI 5.64-16.3). Higher odds ratios for females were also seen within each of the major histologic groupings. Thus, the higher elevated risk of lung cancer currently observed in other studies for female ever smokers compared with male ever smokers, while possibly attributable in part to greater smoking cessation among males, may be due to higher susceptibility among females.

Occupational exposure to sulfuric acid in southern Ontario, Canada, in association with laryngeal cancer.

A case-referent study, designed to test associations between asbestos, nickel, and the development of laryngeal cancer, was conducted in southern Ontario in 1977-1979. The cases were individually matched to neighborhood referents for gender and age. This constituted the primary study. Personal interviews had secured tobacco, alcohol, and detailed work histories. To 183 of the male pairs was added retrospective assessments of sulfuric acid exposure for each job, blind of disease status; this constituted the data base for an augmented secondary analysis. Logistic regression revealed statistically significant odds ratios when tobacco and alcohol were controlled. Exposure-response gradients were strongly positive with odds ratios in the range of 1.97 [95% confidence interval (95% CI) 0.63-6.13] for short duration-low level exposure through 6.91 [95% CI 2.20-21.74] for long duration-higher level exposure employing progressively more specific definitions of exposure. Asbestos as a confounder and the interaction terms examined were nonsignificant. These findings are corroborative of those of other studies.

Lung cancer in women in the Niagara Region, Ontario: a case-control study.

A case-control study of the etiology of lung cancer in women was conducted in the Niagara Region of Ontario, because of local concerns about a high incidence of lung cancer. 51 female patients with lung cancer and 45 matched controls were interviewed. Information was collected about active and passive smoking, occupation and residential history. There was a strong association between active cigarette smoking and lung cancer (ever/never odds ratio 10.0; p less than .001) and 85% of the cases of lung cancer were attributed to active cigarette smoking. No other factors were significantly associated with lung cancer; there was weak evidence of an association between urban environment during childhood and lung cancer (p = 0.07). Associations between lung cancer and air pollution, and residential history, were not demonstrated, contrary to public perception. Thus, a previously reported excess of lung cancer in Niagara females is most likely attributable to cigarette smoking.

Radon exposure, cigarette smoking, and other mining experience in the beaverlodge uranium miners cohort.

A nested case-control study within the Beaverlodge Uranium Miners Cohort was undertaken to assess any possible contribution of confounding by smoking and other mining experience to the risk estimate derived from the original cohort study. Next of kin have been interviewed for 46 lung cancer cases and 95 controls enrolled in the Beaverlodge Uranium Miners Cohort Study who died between 1950 and 1980. Confounding by cigarette smoking and other mining experience appears unlikely to have contributed to the relative risk coefficient for exposure to Rn decay products derived in the parent study. Data for smoking and exposure to Rn decay products are consistent with a multiplicative model, although considerable caution must be applied to this interpretation.

Cigarette smoking and cancer of the pancreas: evidence from a population-based case-control study in Toronto, Canada.

Results are reported with respect to smoking data from a population-based case-control study of pancreatic cancer conducted in Toronto, Canada, between 1983 and 1986. Lifetime smoking histories were obtained for 249 cases and 505 controls. A statistically highly significant positive association was observed between lifetime cigarette consumption and risk of pancreatic cancer. There was a rapid decrease in risk with time for those who quit cigarette smoking, the risk for ex-smokers being the same as for lifetime non-smokers between 10 and 15 years after quitting. Limiting exposure to the 15 years prior to diagnosis considerably strengthens the association and leads to a much more clearly defined dose-response relationship with relative risks of 1.88, 4.61, and 6.52 for tertiles of consumption for current cigarette smokers compared with lifetime non-smokers (p trend less than 10(-5)). We conclude that the current data, together with those from previous studies, strongly support a causal relationship between cigarette smoking and risk of pancreatic cancer, and indicate that cessation of smoking is likely to prove a rapidly effective preventive measure for this major type of cancer.

Exposure of nonsmoking women to environmental tobacco smoke: a 10-country collaborative study.

The interpretation and interpretability of epidemiologic studies of environmental tobacco smoke (ETS) depend largely on the validity of self-reported exposure. To investigate to what extent questionnaires can indicate exposure levels to ETS, an international study was conducted in 13 centers located in 10 countries, and 1,369 nonsmoking women were interviewed. The present paper describes the results of the analysis of self-reported recent exposure to ETS from any source in relation to urinary concentrations of cotinine. Of the total, 19.7 percent of the subjects had nondetectable cotinine levels, the median value was 6 ng/mg, and the cut-point of the highest decile was 24 ng/mg. The proportion of subjects misreporting their active smoking habit was estimated at between 1.9 and 3.4 percent, depending on whether cut-points of 50 or 100 ng/mg creatinine were used. Large and statistically significant differences were observed between centers, with the lowest values in Honolulu, Shanghai, and Chandigarh, and the highest in Trieste, Los Angeles, and Athens. Mean cotinine/creatinine levels showed a clear linear increase from the group of women not exposed either at home or at work, to the group of those exposed both at home and at work. Values were significantly higher for women exposed to ETS from the husband but not at work, than for those exposed at work but not from the husband. The results of linear regression analysis indicated that duration of exposure and number of cigarettes to which the subject reported being exposed were strongly related to urinary cotinine. ETS exposure from the husband was best measured by the number of cigarettes, while exposure at work was more strongly related to duration of exposure. After adjustment of number of cigarettes for volume of indoor places, a similar increase in cotinine (5 ng/mg) was predicted by the exposure to 7.2 cigarettes/8 h/40 m3 from the husband and 17.9 cigarettes/8 h/40 m3 at work. The results indicate that, when appropriately questioned, nonsmoking women can provide a reasonably accurate description of ETS exposure. Assessment of individual exposure to ETS should focus on daily duration and volume of indoor places where exposure occurred.

Dietary factors and risk of lung cancer: results from a case-control study, Toronto, 1981-1985.

Associations between dietary factors and risk of lung cancer are reported from a study of 839 cases and 772 population-based controls interviewed in metropolitan Toronto between 1981 and 1985. Increased consumption of vegetables is associated with a decreased relative risk of 0.60 (95% confidence limits = 0.40 to 0.88) for those in the highest compared with the lowest quartile. Cholesterol intake is associated with increased risk, but this is restricted to those in the highest quartile for whom the relative risk is 1.58 (95% confidence limits = 1.05 to 2.38) compared with those in the lowest quartile. The results of this study suggest that dietary factors may affect the risk of lung cancer, but identification of the specific constituents involved will require further research.

Risk of bladder cancer by source and type of tobacco exposure: a case-control study.

The association between tobacco use and risk of bladder cancer was investigated in a population-based case-control study conducted in Alberta and south-central Ontario, Canada, between 1979 and 1982. In all, 826 histologically-confirmed cancer cases and 792 randomly selected controls, individually matched to cases for age, sex, and area of residence, were recruited into the study. Compared to those who had never smoked cigarettes, males and females who had ever smoked cigarettes had a statistically highly significant 2-fold increase in risk of bladder cancer; for ex-smokers, the risk was intermediate between that for current smokers and never-smokers. There was a dose-dependent increase in risk of bladder cancer with total lifetime cigarette consumption, of similar magnitude for males and females. In males, risk increased with self-reported degree of inhalation in ex-smokers and in current smokers (statistically significant trend), while in females there was no association in current smokers, and a statistically significant inverse association in ex-smokers. Overall, risks of bladder cancer associated with lifetime consumption of plain and filter cigarettes were similar, and there was little evidence to suggest that switching from plain to filter cigarettes was beneficial. Neither passive smoking nor other forms of tobacco consumption (pipes, cigars, chewing tobacco, or snuff) were associated with altered risk of bladder cancer. The population attributable risk for cigarette smoking was about 47% in males and about 33% in females.

An exploratory case-control study of brain tumors in children.

An exploratory case-control study of childhood brain tumors was conducted in southern Ontario between 1977 and 1983, on 74 cases and 138 age- and sex-matched population controls. A significantly elevated risk (perhaps due to early case symptoms) was seen for skull X-rays at least 5 years prior to diagnosis, and for head or neck injuries which required medical attention. However, no evidence of an increased risk appeared for exposure to sick pets or to pesticides, maternal or paternal history of smoking, and various birth characteristics or antenatal exposure of the child, though these have previously been reported to be associated with childhood brain tumors. With respect to the hypothesis that N-nitroso compounds may be involved in the etiology of childhood brain tumors, most exposures of this type were not associated with risk, though a significant positive association was seen for consumption of beer by the mother during pregnancy, and a significant negative association was seen with consumption of fruit juice by the child. Other findings in the present study include an association with developmental problems relating to height and weight and with certain socioeconomic characteristics of the mother. Further investigation of these results in future studies is warranted.

Occupational factors and the incidence of cancer of the bladder in Canada.

During 1979-82, a case-control study of occupational factors and urinary bladder cancer was conducted in Edmonton, Calgary, Toronto, and Kingston, Canada. A total of 826 histologically verified cases of cancer were individually matched by sex, age, and area of residence to 792 randomly selected population controls. Subjects were specifically asked about employment in several industries thought relevant to risk of bladder cancer. Information was also obtained on lifelong occupational history, with special attention given regarding exposures to fumes, dusts, smoke, and chemicals. In addition, subjects provided data on past medical and residential history, on intake of certain dietary items, and on exposure to tobacco and other lifestyle factors. Conditional logistic regression methods were used for the analysis. Under adjustment for cumulative lifetime cigarette consumption, it appeared that for both men and women, most of the occupational factors examined were not associated with significant alteration in risk of bladder cancer. For exposures during the period eight to 28 years before diagnosis, however, raised risk was suggested for men employed at least six months in the chemicals industry (odds ratio = 2.37, p = 0.004), in dye manufacturing or the dyeing of cloth (OR = 3.62 and 4.63, p = 0.041 and 0.035, respectively), as tailors (OR = 3.85, p = 0.015), or in jobs in which contact with diesel or traffic fumes occurred (OR = 1.69, p = 0.0008). Increased risk was also seen for men occupationally exposed to tars or asphalt (OR = 3.11, p = 0.019). This study then, at least for men, supports perhaps a few of the suspect industries as related to risk of bladder cancer.

Dietary factors and the incidence of cancer of the urinary bladder.

A case-control study of diet and bladder cancer was conducted during 1979-1982 in Edmonton, Calgary, Toronto, and Kingston, Canada. A total of 826 histologically verified cancer cases were individually matched by age, sex, and area of residence to 792 randomly selected population controls. Subjects were interviewed concerning their histories of exposure to a number of dietary factors, including table-top artificial sweeteners, low calorie foods and drinks, beverages containing caffeine or ethanol, and certain other food items. Also, subjects provided information on their past medical, occupational, and residential histories, in addition to their exposures to tobacco and other life-style factors. For the analysis, conditional logistic regression methods were used. Under adjustment for cumulative lifetime amount of cigarette smoking, the dietary factors, with little exception, were not associated with significant alteration of risk for bladder cancer. In particular, ever regular use of artificial sweeteners did not appear to be associated with increased risk, either among men (odds ratio = 0.95, p = 0.70) or among women (odds ratio = 1.15, p = 0.53). However, daily intake of cholesterol, calculated from reported frequencies of consumption of nine relevant food items, suggested a mild increase in risk; the odds ratio estimate of trend was 1.07/100 mg average daily intake (i.e., 1.07(5.5) = 1.45 for 550 mg cholesterol per day, as might be consumed in one egg; p = 0.009). A history of diabetes mellitus of onset after age 20 years also seemed to be associated with increased risk of bladder cancer (odds ratio = 1.65, p = 0.019), but this increase did not appear to be the result of use of insulin or other medications, or use of artificial sweeteners or low calorie foods. Thus, this study tends to confirm reports of a lack of association between use of artificial sweeteners and subsequent risk of bladder cancer.

The reliability of passive smoking histories reported in a case-control study of lung cancer.

A test-retest design has been used to examine the reliability of passive smoking histories reported in personal interviews. A total of 117 control subjects initially interviewed in a lung cancer case-control study conducted in metropolitan Toronto, Canada, between 1983 and 1984 were reinterviewed on average six months later. Responses to initial screening questions used to detect a person's exposure to passive smoke were more reliable for residential than for occupational exposure. Respondents also more reliably reported residential exposure to spouse's passive smoke than to the passive smoke of others at home. Quantitative measures of exposure to passive smoke, i.e., number and duration of exposure, were even less reliably reported. Nonsmoking respondents gave the most reliable information. The low reliability of self-reported duration of exposure to passive smoke is consistent with the inability of several studies to detect a significant dose-response relation with lung cancer risk when measures of dose that depend solely on duration are used.