Vegetable consumption and lung cancer risk: a population-based case-control study in Hawaii.

We conducted a population-based study of diet and lung cancer among the multiethnic population of Hawaii in 1983-1985. We completed interviews for 230 men and 102 women with lung cancer and 597 men and 268 women controls, frequency-matched to the patients by age and sex. A quantitative dietary history assessed the usual intake of foods rich in vitamins A and C and carotenoids. A clear dose-dependent negative association was demonstrated between dietary beta-carotene and lung cancer risk in both sexes. After adjusting for smoking and other covariates, the men in the lowest quartile of beta-carotene intake had an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol, vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.

Vitamin A and prostate cancer in elderly men: enhancement of risk.

Vitamin A intake was assessed from dietary histories on 452 men with prostate cancer and 899 population controls in Hawaii during the period 1977-1983. In the group of men less than 70 years of age, there were no significant associations of this nutrient with risk for prostate cancer. In the men greater than or equal to 70 years, however, risk increased directly with the amount of vitamin A consumed (relative risk of 2.0 for the highest relative to the lowest intake quartile, and a significant linear trend, P less than 0.01). The findings were similar for the various components of vitamin A but were somewhat stronger for total carotenes than for total retinol. These results were generally consistent across the five ethnic groups and were not affected by statistical adjustment for dietary fat. Possible mechanisms for this risk enhancement by vitamin A in elderly men are proposed.

Cancer occurrence in shipyard workers exposed to asbestos in Hawaii.

Because large numbers of persons were employed in United States shipyards during World War II, the long-term risks for cancer associated with asbestos exposure in this setting are of great concern. We report here on the mortality findings after up to 29 years of follow-up on a retrospective cohort of 7971 male Pearl Harbor Naval Shipyard workers, which included more than 3000 men whose employment period spanned the World War II years. Compared with the general population of Hawaii, workers in the shipyard cohort had no increase in total mortality or in total cancer mortality irrespective of the duration of their exposure. However, the risk ratio for lung cancer among workers with at least 15 years of asbestos exposure was 1.4 overall (95% confidence interval, 1.0 to 2.0) and 1.7 for those with a latency interval of 30 or more years (95% confidence interval, 1.0 to 2.5). In addition, seven mesotheliomas occurred between 1977 and 1982 in a subset of the cohort, consisting of 7029 Hawaii residents who are being followed prospectively for cancer incidence. This represented an incidence of 67.3 per million men per year, compared with a rate of 5.8 for the state as a whole. These results suggest that the long-term relative increase in risk for mesothelioma may be even greater than that for bronchogenic carcinoma in this and other cohorts of United States shipyard workers exposed to asbestos.

Relationship of alcohol consumption to diet: a population-based study in Hawaii.

The relationship of alcohol use to diet was examined in 2272 male and 2337 female adults aged 45 y and older who provided a quantitative diet history during 1977-1979. Mean values for each dietary variable, adjusted for smoking, ethnicity, income, and education, were compared in each sex between abstainers and drinkers and by tertile of ethanol intake. Linear relationships with extent of drinking were also sought. Drinkers were found to be less obese than abstainers. Consumption of carbohydrate, vitamins, calcium, fruits, fruit juices, and raw vegetables was greater among abstainers whereas consumption of fat (particularly polyunsaturated fatty acids), cholesterol, zinc, meat, pickled vegetables, and dried fish was greater among drinkers. Because validations of dietary questionnaires have shown that alcohol consumption is more accurately recalled than food intake, the possibility of a residual confounding effect for these dietary variables should be considered in epidemiologic studies of alcohol and health.

Prospective serial analysis of interleukin-2 and soluble interleukin-2 receptor in relapsing-remitting multiple sclerosis.

We performed a longitudinal analysis of serum interleukin-2 (IL-2) and soluble IL-2 (sIL-2R) concentrations in 60 patients with relapsing-remitting (R-R) multiple sclerosis (MS) as well as in 33 age- and sex-matched normal controls. Overall, we found that serum IL-2 levels remained low (less than 10 U/ml) and did not change appreciably over time; however, marked fluctuations in sIL-2R levels were observed in both the patient and control groups. Using patients as their own controls, we calculated an interrelapse (disease stable) mean sIL-2R concentration as a baseline for comparison with relapse values; sIL-2R levels greater than the 90th percentile of the Student's t distribution of stable values were defined as "peaks." There were a total of 27 sIL-2R peaks, eight (30%) of which correlated with clinical relapses but were potentially predictive of only 18% (8/45) of all the recorded clinical relapses. There was no difference in disease severity (Expanded Disability Status Scale) score between peak-correlated and noncorrelated relapses. Our data suggest that despite reports of elevated levels of IL-2 and sIL-2R in MS, neither may be a useful marker for predicting clinical disease activity in R-R MS.

Dietary factors in lung cancer prognosis.

A hypothesis-generating analysis of the role of diet on survival was conducted among a sample of 463 men and 212 women with histologically-confirmed lung cancer. Interview information was obtained from two population-based case-control studies of lung cancer conducted on the Island of Oahu, Hawaii, between 1979 and 1985. The interview consisted of a quantitative dietary history to assess the usual intake of foods 1 year prior to diagnosis, a complete tobacco history, and other demographic and lifestyle information. Records from the Hawaii Tumor Registry were reviewed for data on stage, histology, and follow-up status of these patients. A food group analysis showed a significant reduction in the risk of death with increasing consumption of all vegetables combined among women (P for trend = 0.03), but not among men. The covariate-adjusted median survival times for women from the highest to the lowest quartiles of vegetable intake were 33, 21, 15, and 18 months, respectively. The results also suggested an association of fruit intake and survival among women (P for trend = 0.02), although a similar effect was not found among men. Increased consumption of certain foods, such as tomatoes and oranges among men, and broccoli and, perhaps, tomatoes among women, appeared to improve survival. This exploratory analysis provides mixed indications that certain components of vegetables and fruits may prolong survival in lung cancer patients.

Lifetime occupational physical activity and prostate cancer risk.

The authors compared the lifetime occupational physical activity of 452 prostate cancer cases identified through the population-based Hawaii Tumor Registry and 899 population controls interviewed from 1981 to 1983. Each job reported was classified into one of five levels of physical activity using published sources. Among men aged 70 years or older, a negative association was found between prostate cancer risk and proportion of life spent in jobs involving only sedentary or light work. Compared with men never employed in such jobs, men who spent more than 54% of their life in these jobs had an odds ratio of 0.5 (95% confidence interval 0.3-0.9). This negative association was dose-dependent, consistent across ethnic groups, and unrelated to socioeconomic status, dietary risk factors, or job-related chemical exposures. The findings for younger men were less clear, but not inconsistent with those for older men. Surprisingly, no association was found with years spent in moderately active or very active jobs in either age group. Although inconclusive, these results suggest that physical activity may be positively associated with the risk of prostate cancer, but this association is likely to be weak and indirect.

Descriptive epidemiology of thyroid cancer in Hawaii.

Data were analyzed from 1110 thyroid cancer cases between 1960 and 1984 identified by the Hawaii Tumor Registry, a population-based Statistics, Epidemiology and End Results (SEER) participant covering the entire state of Hawaii. Incidence rates for men and women were relatively stable during this 25-year period. The overall age-adjusted rates were 8.1 per 100,000 for women and 3.1 per 100,000 for men. There was a significant variation in incidence on the basis of ethnicity, with the highest rates for women occurring in Filipinos (18.2 per 100,000) and for men in Chinese (6.3 per 100,000). A comparison of different populations around the world showed that Hawaii has some of the highest reported incidence rates for thyroid cancer. In addition, a comparison of ethnic-specific incidence rates for groups living in Hawaii with people of the same ethnic backgrounds living in other geographic areas showed that Hawaii residents generally have much higher rates, suggesting that environmental influences are responsible for the unusually high rates in Hawaii.

Smoking, alcohol, occupation, and hair dye use in cancer of the lower urinary tract.

This case-control study was based on 137 Caucasian and 124 Japanese cases of urinary tract cancer identified in Hawaii between 1977 and 1986. Each case was matched on sex, age, and race to two population-based controls. Heavy cigarette smokers (41 or more pack-years for men; 21 or more pack-years for women) had a significantly elevated risk compared with nonsmokers (odds ratio (OR) = 6.2, 95% confidence interval (CI) 3.4-11.1 for the men; OR = 2.8, 95% CI 1.2-6.3 for the women). When the men and women were combined, employment in high-risk industries (includes machinery, automotive, and textiles, among others) was significantly associated with cancer risk (OR = 1.6, 95% CI 1.1-2.3). Alcohol intake and hair dye use showed weaker positive associations with risk that were not statistically significant.

Validation of body size information on driver's licenses.

Weight and height values measured in a population-based case-control study of breast cancer conducted in Hawaii were used to validate body size information recorded on driver's licenses. It is concluded that this information is sufficiently accurate to justify the use of driver's license registration files as a means of assembling large prospective or historical cohorts to study the health hazards of obesity.

Diet and prostatic cancer: a case-control study in Hawaii.

A total of 452 cases of prostatic cancer identified through the population-based Hawaii Tumor Registry during the period 1977-1983 and 899 age-matched population controls were interviewed on the island of Oahu from 1981 to 1983. All interviews of the subjects, who comprised five different ethnic groups, were conducted in the home by use of a quantitative dietary history method. Usual weekly intake of fat, zinc, and vitamins A and C, including supplements, was determined for each subject. Among men 70 years or older, but not among younger men, and mean weekly consumption of saturated fat, carotenes, and zinc, adjusted for age and ethnicity, was greater for cases than for controls. In a multiple logistic regression analysis, the odds ratio for the highest quartile of fat intake among the older men was 1.7 (95% confidence interval (CI) 1.0-2.8). The corresponding odds ratios were 1.6 (95% CI 1.0-2.5) for carotenes, 1.4 (95% CI 0.9-2.3) for total vitamin C, and 1.7 (95% CI 1.1-2.7) for total zinc. There were significant linear trends in the odds ratios for saturated fat and zinc, but no synergistic interactions among the nutrients. The findings suggest that several different components of the diet may contribute independently to the risk of prostatic cancer in elderly men.

Reproducibility of a diet history in older men in Hawaii.

A diet history method was tested for reproducibility among 106 older men from the five major ethnic groups (Japanese, Caucasian, Hawaiian, Filipino, and Chinese) of Hawaii. The questionnaire, administered by trained interviewers, was designed to estimate the dietary intakes of total and saturated fat, cholesterol, vitamin A, beta-carotene, vitamin C, and zinc. Subjects were asked to recall their usual frequencies and amounts of consumption during a usual month of more than 100 food items, along with the intake of seasonal foods with a high vitamin A content. A second interview was conducted 1-14 months later to obtain a diet history covering the same time period as the first interview. The same questionnaire was utilized in both interviews. The effects of ethnicity, age, and recall interval (period between the diet reference date and initial interview) on the reproducibility of nutrient intakes were examined. The intraclass correlation coefficient (rI) and the weighted kappa statistic (Kw) were used to assess agreement. The overall levels of reproducibility were relatively good. Neither ethnicity, age, nor length of recall period had a major effect on reproducibility. The data suggested that this diet history method is an appropriate instrument for estimating the usual dietary intakes of a healthy heterogeneous group of older men in Hawaii.

Incidence trends and ethnic patterns for childhood leukaemia in Hawaii: 1960-1984.

We analysed data obtained from the Hawaii Tumor Registry, a population-based participant in the Surveillance, Epidemiology, and End Results (SEER) programme that monitors cancer incidence and mortality for the entire state. A total of 138 males and 116 females, under the age of 15, were diagnosed with leukaemia between 1960 and 1984, with average annual age-adjusted incidence rates of 49.6 and 44.8 per million, respectively. Time trend analysis by 5-year calendar periods revealed an increasing rate for leukaemia among females only, whereas other populations have shown a positive trend in both sexes. The incidence rates for all ethnic groups combined were similar to those for US whites. Japanese and Chinese males had a slightly higher rate for leukaemia than US whites, while Filipinos, Hawaiians and whites in Hawaii had relatively lower rates. Among females, incidence was higher among whites, Filipinos, Hawaiians and Chinese than among US whites, and lower among Japanese. Thus, there were notable sex differences in the ethnic distribution of this disease.

Ethnic patterns of childhood cancer in Hawaii between 1960 and 1984.

Cases of childhood cancer (less than 15 years of age at diagnosis), diagnosed between 1960 and 1984, were obtained from the Hawaii Tumor Registry, a population-based Surveillance, Epidemiology, and End Results (SEER) participant covering the entire State of Hawaii. During the 25 years of data collection, cancer was diagnosed in 398 males and 302 females, with overall age-adjusted incidence rates of 140.5 and 112.2 per million, respectively. Leukemia was the leading cause of childhood cancer, accounting for over 1/3 of diagnoses during the study period. Standardized incidence ratios (SIR) were calculated for each ethnic-sex group separately based on US white age-specific incidence rates for 1973 to 1982 from the SEER program. Overall, incidence rates for childhood cancer in Hawaii were generally similar to those found in all SEER areas.

Pharmacokinetics of recombinant human interferon-beta ser in healthy volunteers and its effect on serum neopterin.

The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcutaneous (sc) doses. Blood samples collected after the iv, first sc, and last sc doses and prior to each sc dose were assayed for interferon antiviral activity and the interferon-inducible marker neopterin. Following iv administration, serum interferon concentrations generally declined biexponentially, with a mean serum clearance of 0.76 +/- 0.28 L/hr-kg, a mean steady-state volume of distribution of 2.88 +/- 1.81 L/kg, and a mean terminal half-life of 4.29 +/- 2.29 hr as determined by noncompartmental analysis. Following sc administration, absorption of rIFN-beta ser was prolonged, with serum concentrations generally below 100 IU/mL. No accumulation of rIFN-beta ser in serum was noted after eight daily sc injections. In contrast, serum neopterin levels did not increase above baseline levels until 12 hr after iv dosing and 24 hr after sc dosing. The mean increase in serum neopterin at 24 hr post iv injection was significantly greater than that at 24 hr post sc dosing.

Validation of a quantitative diet history method in Hawaii.

The validity of a quantitative diet history method was evaluated among 262 men and women from the five major ethnic groups of Hawaii (Japanese, Caucasian, Chinese, Filipino, and Hawaiian) in 1984-1987. The reference data included four 1-week food records obtained at approximately 3-month intervals. The diet history was administered 6 months after the fourth week of food records and included 47 foods that were major sources of protein, fat, cholesterol, vitamins A and C, and beta-carotene. Photographs showing three portion sizes were utilized for quantifying intakes in the food records and the diet history. Generally, among all ethnic-sex groups, intakes from the diet history were greater than those from the record sets, particularly for the vitamins. Agreement was measured by the intraclass correlation coefficient (rl) and the weighted kappa statistic (kappa w), and consistency was measured by Spearman's rank correlation (rho). For the total group, the rl's ranged from 0.48 for vitamin A to 0.61 for cholesterol. The kappa w's were generally lower than the rl's, whereas the rho's were higher, ranging from 0.52 for vitamin C to 0.64 for cholesterol. Agreement among the ethnic-sex groups varied, with the Chinese females and the Japanese males having the higher rl's, and the Hawaiian males and females having the lowest values. The results provide evidence that the quantitative diet history gives reasonably accurate estimates of the usual dietary intakes among the major ethnic groups of Hawaii.

Dietary factors in cancer of the lower urinary tract.

This dietary study was based on 195 male and 66 female cases of lower urinary tract cancer, identified in Hawaii between 1977 and 1986. Each case was matched for sex, age, and ethnic group (Caucasian or Japanese) to 2 population-based controls. There was a decrease in risk with increasing levels of consumption of vitamin C in women (p = 0.03) and dark green vegetables in men (p = 0.02). When examined by quartile, the odds ratios for the highest quartile of intake compared to the lowest quartile were 0.4 for women and 0.6 for men, respectively. Although dark green vegetables are a source of carotenoids, the intake of total carotenoids, retinol and total vitamin A was weakly and inconsistently related to risk in both sexes. Among women only, there was also an inverse association with the consumption of regular ground coffee (p = 0.02) but not with other types of coffee. Finally, there were no statistically significant or consistent differences between cases and controls in the intake of artificial sweeteners and tea.

Comparison of long-term dietary recall between cancer cases and noncases.

A quantitative history of current dietary intake based on 83 food items was administered by interview to a representative sample of 4,809 subjects in Hawaii in 1977-1979. In 1983-1987, this history was readministered to the 131 original respondents who had subsequently developed cancer, as well as 413 randomly selected subjects who remained cancer free. A surrogate was interviewed when the original subject was unavailable. The repeat interview elicited information about diet at the time of the original interview. The authors found that recall values for macronutrients were consistently higher than original levels for both cases and noncases, which may be due in part to a modification in the administration of the repeat questionnaire. Although there were no marked differences overall between cases and noncases in the ability to recall past diet, differences between the two groups were seen in certain subsets of the sample. In the subgroup with the longest recall interval (8-10 years), cases were not able to recall their diets as well as noncases. Also, the difference between original and recall values was larger for cases with colorectal cancer and all cases diagnosed with distant stage disease, compared with noncases. This was not true for cases of breast and prostate cancer and those with localized or regional disease. The following variables were found to have no significant effect on recall for cases or noncases: sex, age, education, and type of respondent (surrogate or subject). Of the five major ethnic groups included in the study, Japanese had the best recall of their past diets, while respondents reporting a diet change between the interviews had poorer recall than did those who reported no change. These results suggest that differential misclassification in dietary case-control studies may pose a significant problem in certain instances, but that these studies can yield meaningful results with certain constraints on the study population.

Beta-carotene and canthaxanthin inhibit chemically- and physically-induced neoplastic transformation in 10T1/2 cells.

We have studied the effects of beta-carotene (beta-C), a vitamin A precursor of plant origin, and canthaxanthin (CTX), a non-provitamin A carotenoid, on the neoplastic transformation of C3H/10T1/2 murine fibroblast cells. Chemical transformation in this well-characterized cell system has previously been shown to be reversibly inhibited by retinoids, compounds with vitamin A-like activity. Here we show that both beta-C and CTX inhibit 3-methylcholanthrene (MCA)-induced transformation with ED50s of 9 x 10(-7) M and 2 x 10(-7) M, respectively. Both carotenoids failed to inhibit X-ray-induced transformation when the cells were treated prior to and during irradiation. However, when the drugs were added 1 week after X-irradiation and maintained in the medium thereafter, as in the chemical transformation protocol, both carotenoids inhibited subsequent development of transformed foci in a dose-dependent manner. Again, CTX was more effective than beta-C, such that 3 x 10(-6) M completely inhibited radiogenically-induced foci. Similar to the previously described action of retinoids, the inhibition of MCA-induced transformation was reversible; upon removal of the drug, transformed foci developed within 2 weeks, indicating that the carotenoids were not specifically toxic to initiated cells. Although both carotenoids caused a small dose-dependent decrease in the growth rate of both parental and initiated 10T1/2 cells, they did not markedly affect colony size or number when the cells were treated as in the transformation assays, nor did they influence the expression of neoplasia of two transformed cell lines. Although the actions of beta-C and CTX are similar to those of retinoids in the 10T1/2 system, we suggest that the carotenoids act via a different mechanism, since CTX cannot be converted to active retinoids in mammalian cells, and there is no evidence that 10T1/2 cells can convert beta-C to vitamin A. We suggest that the carotenoids' lipid anti-oxidant properties may be responsible for their inhibitory actions on transformation.

The effect of dietary cholesterol and fat on the risk of lung cancer in Hawaii.

A population-based case-control study of the association between dietary lipids and lung cancer was carried out in Hawaii between March 1983 and October 1985. The sample included 226 men and 100 women with lung cancer and 597 male and 268 female controls, frequency-matched to the cases on sex and five-year age group. Personal interviews were conducted in the home by trained interviewers using a quantitative diet history method. The items in the questionnaire were chosen to provide an estimate of 85% or more of the intakes of dietary cholesterol and fat for individuals in each of the five ethnic groups included in the study. The results showed a significant positive association of dietary cholesterol and the risk of lung cancer in men, but not in women. The odds ratio for the risk of lung cancer among men in the highest compared with the lowest quartile of cholesterol intake was 2.2 (95% confidence interval 1.3-3.8). Although there was a significant trend (p less than 0.05), the effect of cholesterol suggested a threshold rather than a continuous gradient. The association of cholesterol and lung cancer was consistent for three of four ethnic groups analyzed separately. These results confirmed earlier findings by these investigators. The effect of cholesterol on the development of lung cancer was restricted to current cigarette smokers who smoked tobacco heavily and to squamous and small cell histologic types of lung cancer. Similar results were found for total, saturated, and, to some extent, unsaturated dietary fat, but because of the high correlation between fat and cholesterol (r = 0.76 for total fat and cholesterol), it was not possible to separate the effects of these nutrients.