Paul K. Mills

Cohort study of diet, lifestyle, and prostate cancer in Adventist men.

Dietary and lifestyle characteristics were evaluated in relation to subsequent prostatic cancer risk in a cohort of approximately 14,000 Seventh‐day Adventist men who completed a detailed lifestyle questionnaire in 1976 and who were monitored for cancer incidence until the end of 1982. During the 6‐year follow‐up period, 180 histologically confirmed prostatic cancers were detected among some 78,000 man‐years of follow‐up. Increasing educational attainment was associated with significantly decreased risk of prostate cancer in this study; age at first marriage was also inversely associated with risk, although this was not significant. There was no relationship between body mass index (as measured by Quetelets Index) and risk. A history of prostate “trouble” was associated with a 60% increase in risk which was highly significant. Although there were suggestive relationships between increasing animal product consumption and increased risk, these results did not persist after accounting for the influence of fruit and vegetable consumption. Nor was exposure to the vegetarian lifestyle during the childhood years associated with alterations in subsequent risk. However, increasing consumption of beans, lentils and peas, tomatoes, raisin, dates, and other dried fruit were all associated with significantly decreased prostate cancer risk.

Dietary habits and past medical history as related to fatal pancreas cancer risk among adventists

Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case—control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh‐day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow‐up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease‐inhibitor content are more important than any increase in pancreas cancer risk attendent on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.

Long-term Ambient Concentrations of Total Suspended Particulates, Ozone, and Sulfur Dioxide and Respiratory Symptoms in a Nonsmoking Population

Seventh-day Adventist nonsmokers, who, subsequent to 1966, had resided within 8 km (5 miles) of their 1977 residence (N = 3,914), completed the National Heart and Lung Institute (NHLI) respiratory symptoms questionnaire in 1977 and again in 1987. For each participant, cumulative ambient concentrations of total suspended particulates (TSP), ozone, and sulfur dioxide (SO2) in excess of several cutoff levels were estimated by month and by interpolating ambient concentrations from state air-monitoring stations to their residential and workplace zip codes for the month. Statistically significant relationships between ambient concentrations of TSP and ozone, but not SO2, were found with several respiratory disease outcomes. Multivariate analyses adjusted for past and passive smoking and occupational exposures. Results are discussed within the context of standards setting for TSP and ozone.

Dietary habits and breast cancer incidence among seventh-day adventists

Breast cancer incidence was monitored in a cohort of 20,341 California Seventh‐day Adventist women who completed a detailed lifestyle questionnaire in 1976, and who were followed for 6 years. There were 215 histologically confirmed primary breast cancer detected among some 115,000 person‐years of follow‐up. Mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. Established risk factors for breast cancer showed strong relationships to risk in these data. Age at first live birth, maternal history of breast cancer, age at menopause, educational attainment, and obesity were all significantly related to risk. However, increasing consumption of high fat animal products was not associated with increased risk of breast cancer in a consistent fashion. Nor were childhood and early teenage dietary habits (vegetarian versus nonvegetarian) related to subsequent, adult risk of developing breast cancer. Also, a derived index of percent of calories from animal fat in the adult years was not significantly related to risk. These results persisted after simultaneously controlling for other, potentially confounding variables, utilizing Cox proportional hazard regression models.

Chronic disease among seventh‐day adventists, a low‐risk group. Rationale, methodology, and description of the population

The Adventist Health Study is a prospective cohort study of 34,198 non‐Hispanic white Seventh‐day Adventists (13,857 men; 20,341 women, age 25–100 years) followed for 6 years (1977–1982). Within this population, 55.2% were lacto‐ovovegetarian (consumed meat, poultry, or fish less than one time per week with no restrictions as to egg or dairy product consumption) in 1976 and most abstained from alcohol, tobacco, and pork products. Baseline data included demographic variables, information on current and past dietary habits, exercise patterns, use of prescription drugs, use of alcohol and tobacco, measures of religiosity, occupation and residential histories, anthropometric data, and menstrual and reproductive histories. Nonfatal case ascertainment was completed through review of self‐reported hospitalizations obtained from annual self‐administered mailed questionnaires and through computerized record linkage with two California population‐based tumor registries. Fatal case ascertainment was completed via record linkage with computerized California state death certificate files, the National Death Index, and individual follow‐up. During the 6 years of follow‐up, 52.8% of the 34,198 study subjects reported at least one hospitalization. A total of 20,702 medical charts were reviewed for cancer and cardiovascular disease incidence and 1406 incident cancer cases and 2716 deaths from all causes were identified after baseline data collection.

Prospective study of exogenous hormone use and breast cancer in seventh‐day adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh‐day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow‐up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12–2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00–1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71–2.85).

Correlation analysis of pesticide use data and cancer incidence rates in California counties.

California, the leading agricultural state in the United States, has maintained a population-based cancer registry since 1988, and it also maintains a comprehensive, state-wide pesticide reporting system. Data on cancer incidence and pesticide use reporting are available, by county, for all 58 counties in California. Average annual age-adjusted cancer incidence rates (1988-1992), on a county-, sex-, and race/ethnicity-specific basis, were obtained from the California Cancer Registry (CCR), which maintains the population-based cancer registry throughout California. Pesticide use data (i.e., pounds of active ingredient applied annually in each county) were obtained from the California Department of Pesticide Regulation for 1993. Investigators used Pearson product-moment correlation coefficients (r) to correlate age-adjusted incidence rates for selected cancers with the use data for selected pesticides. For most sex- and race/ethnicity-specific groups, the correlation coefficients were very close to zero or negative in sign, indicating no correlation between pesticide use and cancer incidence. There were, however, several exceptions, particularly in Hispanic males for whom the following correlations were observed: leukemia and atrazine (r=.40), leukemia and 2,4-dichlorophenoxyacetic acid (r=.41), leukemia and captan (r=.46), atrazine and brain cancer (r=.54), and atrazine and testicular cancer (r=.41). For black males, we observed the following: atrazine and prostate cancer (r=.67) and Captan and prostate cancer (r=.49). In females, only a few of the correlations were elevated. Although most of the correlations examined in this analysis were not elevated, several of those in the Hispanic and black male populations were. These segments of the population have traditionally been employed as farm workers in California and have had the greatest potential for exposure to pesticides. This was an ecological study for which no data about exposure to pesticides at the individual level were available for analysis. In addition, no latency period was allowed between potential exposure and diagnosis with cancer. However, the results obtained in two minority groups who represented the majority of farm workers in the fields suggested that additional research studies, in which more rigorous study designs are used, should be conducted in those groups.

Estimated Long-Term Ambient Concentrations of PM10 and Development of Respiratory Symptoms in a Nonsmoking Population

Site- and season-specific regressions of particulates less than 10 mu in diameter (PM10) on total suspended particulates (TSPs) were formed throughout California during years when both were monitored. The regressions were then applied to monitored TSPs for the years 1973 to 1987, and indirect estimates of PM10 were formed. These estimates of PM10 were validated by interpolating them to other monitoring stations. The split-halves correlation between the estimated and monitored mean concentrations, obtained when both were first cumulated for a 2-y period, was .86. Indirect estimates of PM10 at monitoring stations were interpolated, by month, to zip code centroids of home and work location and were cumulated for a cohort of 3,914 California Seventh-day Adventist (SDA) nonsmokers. Multivariate analyses, adjusted for several covariates, showed statistically significant (p < .05), but small, positive associations between PM10 and development of (a) definite symptoms of overall airway obstructive disease, (b) chronic productive cough, and (c) increased severity of airway obstructive disease and asthma. The relative risk (RR) associated with 1,000 h/y (42 d) exposure to concentrations of PM10 that exceeded 100 micrograms/m3 for development of airway obstructive disease was 1.17 (95% confidence interval [CI]: 1.02, 1.33); for development of productive cough, the RR was 1.21 (CI 1.02, 1.44); and for development of asthma, the RR was 1.30 (CI, 0.97, 1.73). Stronger associations were observed for those who were exposed occupationally to dusts and fumes. The RR of developing airway obstructive disease as an adult for those who had airway obstructive disease as a child was 1.66 (CI 1.15, 2.33).

Long-term ambient concentrations of total suspended particulates and oxidants as related to incidence of chronic disease in California Seventh-Day Adventists.

Cancer incidence and mortality in a cohort of 6000 nonsmoking California Seventh-Day Adventists were monitored for a 6-year period, and relationships with long-term cumulative ambient air pollution were observed. Total suspended particulates (TSP) and ozone were measured in terms of numbers of hours in excess of several threshold levels corresponding to national standards as well as mean concentration. For all malignant neoplasms among females, risk increased with increasing exceedance frequencies of all thresholds of TSP except the lowest one, and those increased risks were highly statistically significant. For respiratory cancers, increased risk was associated with only one threshold of ozone, and this result was of borderline significance. Respiratory disease symptoms were assessed in 1977 and again in 1987 using the National Heart, Lung and Blood Institute respiratory symptoms questionnaire on a subcohort of 3914 individuals. Multivariate analyses which adjusted for past and passive smoking and occupational exposures indicated statistically significantly (p less than 0.05) elevated relative risks ranging up to 1.7 for incidence of asthma, definite symptoms of airway obstructive disease, and chronic bronchitis with TSP in excess of all thresholds except the lowest one but not for any thresholds of ozone. A trend association (p = 0.056) was noted between the threshold of 10 pphm ozone and incidence of asthma. These results are presented within the context of standards setting for these constituents of air pollution.

TESTICULAR CANCER ASSOCIATED WITH EMPLOYMENT IN AGRICULTURE AND OIL AND NATURAL GAS EXTRACTION

A hospital-based case-control study, involving review of the medical records of 347 patients with histologically confirmed germ-cell tumours of the testis and 347 randomly selected controls with other disorders, demonstrated a significant association between this cancer and work in the agricultural industry. The odds ratio for present farming occupation was 6.27 (95% confidence limits 1.83, 21.49; p less than 0.05). Work in the crude petroleum and natural gas extraction industry also conferred excess risk for this cancer (odds ratio 2.29; CL 1.03, 5.11).