Pesticides and cancer risk.
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Environmental Pollution↗
Biomedical subjects
C W Heath
Publications and source records attributed to C W Heath.
Cigarette smoking and changes in the histopathology of lung cancer.
BACKGROUND: Adenocarcinoma of the lung, once considered minimally related to cigarette smoking, has become the most common type of lung cancer in the United States. The increased incidence of this cancer might be explained by advances in diagnostic technology (i.e., increased ability to perform biopsies on tumors in smaller, more distal airways), changes in cigarette design (e.g., the adoption of filtertips), or changes in smoking practices. We examined data from the Connecticut Tumor Registry and two American Cancer Society studies to explore these possibilities. METHODS: Connecticut Tumor Registry data from 1959 through 1991 were analyzed to determine whether the increase in lung adenocarcinoma observed during that period could be best described by birth cohort effects (i.e., generational changes in cigarette smoking) or calendar period effects (i.e., diagnostic advances). Associations between cigarette smoking and death from specific types of lung cancer during the first 2 years of follow-up in Cancer Prevention Study I (CPS-I), initiated in 1959) and Cancer Prevention Study II (CPS-II, initiated in 1982) were also examined. RESULTS: Adenocarcinoma incidence in Connecticut increased nearly 17-fold in women and nearly 10-fold in men from 1959 through 1991. The increases followed a clear birth cohort pattern, paralleling gender and generational changes in smoking more than diagnostic advances. Cigarette smoking became more strongly associated with death from lung adenocarcinoma in CPS-II compared with CPS-I, with relative risks of 19.0 (95% confidence interval [CI] = 8.3-47.7) for men and 8.1 (95% CI = 4.5-14.6) for women in CPS-II and 4.6 (95% CI = 1.7-12.6) for men and 1.5 (0.3-7.7) for women in CPS-I. CONCLUSIONS: The increase in lung adenocarcinoma since the 1950s is more consistent with changes in smoking behavior and cigarette design than with diagnostic advances.
Adenocarcinoma↗
Hypertension, diuretics, and antihypertensive medications as possible risk factors for renal cell cancer.
The authors examined the relation of hypertension, use of diuretics, and use of antihypertensive medications to the risk of fatal renal cell cancer in a prospective cohort study of 998,904 adult Americans followed for 7 years (1982-1989). Analysis included 335 renal cell cancer deaths (123 in women and 212 in men). Cox proportional hazards modeling was used to calculate rate ratios. Increased rate ratios were present for cigarette smoking in men and for elevated body mass index in both sexes. Significantly increased age-matched rate ratios, independent of smoking and body mass index, were present for hypertension, use of diuretics, and use of hypertension medications, but only for women. Multivariate testing confined these risks to hypertensive women who were using hypertension medications alone (rate ratio = 2.2, 95% confidence interval 1.4-3.5) or with diuretics (rate ratio 2.5, 95% confidence interval 1.5-4.3). Risk was not significantly increased for either men or women who had untreated hypertension or who used diuretics alone with or without hypertension. These findings partly support those of earlier studies suggesting that medications related to treatment of hypertension, or the severity of hypertension itself, may contribute to the etiology of renal cell cancer.
Adult↗
Smoking and fatal prostate cancer in a large cohort of adult men.
The authors examined the relation between smoking and the risk of fatal prostate cancer in a large prospective mortality study of 450,279 men who were cancer free at enrollment in 1982. During 9 years of follow-up, 1,748 deaths occurred from prostate cancer. Cox proportional hazards modeling was used to adjust for other risk factors. Current cigarette smoking was associated with fatal prostate cancer (rate ratio = 1.34, 95% confidence interval (CI) 1.16-1.56). The rate ratio was greater at younger ages, decreasing from 1.83 (95% CI 1.04-3.24) among men below the age of 60 years to 1.11 (95% CI 0.79-1.58) among men aged 80 years and above (p for trend = 0.16). No trend in risk was observed with the number of cigarettes per day or with the duration of smoking among current smokers at baseline, and no increased risk was found among former smokers. Race did not significantly modify the association between cigarette smoking and fatal prostate cancer. These data, together with those of three other large prospective studies that find higher death rates from prostate cancer in current cigarette smokers, and inconsistent findings in incidence studies suggest that smoking may adversely affect survival in prostate cancer patients.
Adult↗
Tubal ligation and fatal ovarian cancer in a large prospective cohort study.
Several studies suggest that tubal sterilization may decrease the risk of ovarian cancer. Data from the Cancer Prevention Study II were analyzed to examine the relation between tubal ligation and ovarian cancer mortality in a large prospective study. A total of 396,114 women who had not had hysterectomies and who had no prior history of cancer (except nonmelanoma skin cancer) were followed prospectively for approximately 9 years from 1982 to 1991. During this time, 799 ovarian cancer deaths were observed. Tubal ligation was significantly associated with a decreased risk of ovarian cancer mortality in an age- and race-adjusted Cox proportional hazards model (hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.42-0.96), and the results were essentially unchanged when controlling for potential ovarian cancer risk factors (HR = 0.68, 95% CI 0.45-1.03). The protective effect appeared to be greater in the first 20 years after the procedure (HR = 0.49, 95% CI 0.24-0.99) than later (HR = 0.80, 95% CI 0.48-1.34). No interactions between ever having had a tubal ligation and other covariates were observed. These data suggest that tubal ligation reduces the risk of fatal ovarian cancer.
Adult↗
Molecular pathology of primary and metastatic ductal pancreatic lesions: analyses of mutations and expression of the p53, mdm-2, and p21/WAF-1 genes in sporadic and familial lesions.
BACKGROUND: The molecular pathology underlying the development and progression of ductal pancreatic adenocarcinoma is poorly understood relative to that of other major cancers in industrialized societies. The frequency, nature, and distribution of p53 abnormalities, their temporal relationship to the metastatic and clinicopathologic phenotypes of sporadic and familial pancreatic cancer, and their consequent effects on the genetics and expression of critical wild-type p53-regulated genes (mdm-2 and p21/WAF-1) warrant examination in pancreatic adenocarcinoma. This molecular and immunochemical study of the p53, mdm-2, and p21/ WAF-1 genes and gene products examined the largest series of nonneoplastic, neoplastic, and metastatic ductal pancreatic lesions reported to date in relation to clinicopathologic profile. METHODS: Histologically confirmed specimens of primary (n = 136) and metastatic (n = 23) sporadic and familial ductal pancreatic adenocarcinoma lesions were subjected to immunochemical analyses of p53 expression in which a panel of 3 antibodies was utilized. A panel of nonneoplastic but histologically abnormal pancreatic lesions (n = 77) from individuals with varied histories of cigarette smoking were subjected to similar immunohistochemical examinations. In addition, 3 specimens from patients with chronic pancreatitis, 2 specimens of normal fetal pancreata, and 16 specimens of normal adult pancreata were examined as control tissues. Suitable frozen and archival microdissected tumor lesions were evaluated for mutations in exons 4-9 of the p53 gene by single strand conformation polymorphism (SSCP) and dideoxy sequencing analyses in which two distinct sets of outer and nested intron-based amplification primers were used for each exon. A subset of 25 tumor specimens and 18 tumor-derived cell lines for which the p53 mutation status was known were examined for amplification and/or overexpression of the mdm-2 gene; amplification was determined by Southern hybridization and overexpression by immunohistochemical and Western blot analyses. Similarly, mutations in the coding region of p21/WAF-1 gene were examined by SSCP and DNA sequence analyses, and steady-state expression of the p21/WAF-1 protein was assessed by Western blot analysis in these subsets of tumors and tumor-derived cell lines. RESULTS: Positive ductal nuclear p53 immunostaining was demonstrated in 56% of primary tumors and 54% of metastatic lesions. The frequency did not differ significantly between sporadic and familial lesions, and immunostaining was not observed in ductal, acinar, or islet cell elements of normal pancreata or histologically abnormal benign pancreatic lesions from cigarette smokers. A total of 70% of tumor samples revealed reproducible SSCP abnormalities for p53; 42% of these were found in exons 7 and 8. DNA sequence analysis of cases with greater than 35% epithelial cellularity (n = 25) revealed 17 missense mutations, 12 of which were transitions. Seventy-five percent of these transitions were of G:C-->A:T type. A total of 22% of the p53 mutations identified were microdeletions, along with one insertional mutation at exon 8. None of the normal pancreata from sporadic or familial lesions revealed germ-line p53 alterations. Moreover, the frequency and spectra of p53 alterations exhibited no clear, statistically significant association with tumor grade, TNM stage, or patients' cigarette-smoking histories. The mdm-2 gene was neither amplified nor overexpressed immunochemically in a subset of ductal adenocarcinomas, and there was no clear relationship between the p53 mutation status and the status of the mdm-2 gene or protein. Similarly, SSCP and DNA sequence analysis of the p21/WAF-1 gene revealed only 2 genetic abnormalities in a series of 25 primary tumors and 15 tumor-derived cell lines; 1 of the cell lines also revealed the absence of immunoreactive p21/WAF-1 protein...
Adult↗
Environmental tobacco smoke and lung cancer mortality in the American Cancer Society's Cancer Prevention Study. II.
Environmental tobacco smoke (ETS) has been classified as a human lung carcinogen by the United States Environmental Protection Agency (EPA), based both on the chemical similarity of sidestream and mainstream smoke and on slightly higher lung cancer risk in never-smokers whose spouses smoke compared with those married to nonsmokers. We evaluated the relation between ETS and lung cancer prospectively in the US, among 114,286 female and 19,549 male never-smokers, married to smokers, compared with about 77,000 female and 77,000 male never-smokers whose spouses did not smoke. Multivariate analyses, based on 247 lung cancer deaths, controlled for age, race, diet, and occupation. Dose-response analyses were restricted to 92,222 women whose husbands provided complete information on cigarette smoking and date of marriage. Lung cancer death rates, adjusted for other factors, were 20 percent higher among women whose husbands ever smoked during the current marriage than among those married to never-smokers (relative risk [RR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.6). For never-smoking men whose wives smoked, the RR was 1.1 (CI = 0.6-1.8). Risk among women was similar or higher when the husband continued to smoke (RR = 1.2, CI = 0.8-1.8), or smoked 40 or more cigarettes per day (RR = 1.9, CI = 1.0-3.6), but did not increase with years of marriage to a smoker. Most CIs included the null. Although generally not statistically significant, these results agree with the EPA summary estimate that spousal smoking increases lung cancer risk by about 20 percent in never-smoking women. Even large prospective studies have limited statistical power to measure precisely the risk from ETS.
Adult↗
Contrasting factors associated with abdominal and peripheral weight gain among adult women.
OBJECTIVE: To identify contrasts between the risk factors associated with abdominal weight gain and those associated with peripheral weight gain. DESIGN: Prospective mail survey. SUBJECTS: 44080 white, non-Hispanic, healthy women who were questioned in 1982 (baseline age 40-54 y) and 1992 about weight, diet, alcohol use, smoking, 10 physical activities and other variables. MEASUREMENTS: Self reports in 1992 identified 4261 women who gained weight in the abdomen and 7440 women who gained in the periphery (sites other than the abdomen). Using identical logistic models adjusted for age, baseline body mass index (BMI) and numerous covariates, the abdominal-gain group and the peripheral-gain group were separately compared with 10,888 women who did not gain weight. RESULTS: The likelihood of abdominal gain exceeded that of peripheral gain (by comparison of estimated odds ratios, abdominal vs peripheral) for high meat eaters (1.50 vs 1.15), frequent users of liquor (1.09 vs 0.54), moderate cigarette smokers (0.86 vs 0.59), heavy cigarette smokers (0.96 vs 0.36), cigarette quitters (2.13 vs 1.63), women with high parity (1.52 vs 1.15) and those who reported major weight gain since age 18 y (1.22 vs 0.65). Abdominal gain was less likely than peripheral gain for high vegetable eaters (0.71 vs 0.91), women who exercised > or = 4 h/wk [(especially aerobics/ calisthenics (0.28 vs 0.91) or walking (0.84 vs 1.06)], women who completed menopause (0.74 vs 0.98) and consistent users of estrogen replacement therapy (0.93 vs 1.22). CONCLUSION: A behavior or characteristic may be associated differently with the risks of abdominal and peripheral weight gain. This insight could strengthen recommendations for preventing major chronic diseases.
Abdomen↗
Vitamins may have different effects at different intakes.
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Humans↗
Family history and risk of fatal prostate cancer.
To examine the relation between fatal prostate cancer and family history of prostate cancer in a first-degree relative, we analyzed data from a prospective mortality study of 481,011 men with no history of cancer at enrollment in 1982. During 9 years of follow-up, 1,922 deaths from prostate cancer occurred. Results from Cox proportional hazard models showed that family history of prostate cancer was related to fatal prostate cancer [rate ratio (RR) = 1.60; 95% confidence interval (CI) = 1.31-1.97]; men with two or more affected relatives had a greater than threefold increase in risk (RR = 3.19; 95% CI = 1.51-6.71). Men whose relatives were diagnosed with prostate cancer before age 65 years (RR = 2.03; 95% CI = 1.33-3.09) had a greater effect of family history than men whose relatives were diagnosed at older ages (RR = 1.50; 95% CI = 1.17-1.91). Rate ratios did not increase with decreasing age of the study participants. The 60% increase in risk for men with at least one affected relative is lower than that reported in previous studies.
Adult↗
Stable behaviors associated with adults' 10-year change in body mass index and likelihood of gain at the waist.
OBJECTIVES: The purpose of this study was to identify behaviors associated with change in body mass index or with weight gain at the waist. METHODS: A cohort of 79236 White, non-Hispanic, healthy adults was questioned in 1982 and 1992 about diet and 10 physical activities. Estimates were made of the mean effects of stable behaviors on 10-year change in body mass index and on odds ratios for gain at the waist. RESULTS: Ten-year changes in body mass index was associated positively with meat consumption and smoking cessation and inversely with vegetable consumption, vitamin E supplementation, continued smoking, and some vigorous activities (e.g., jogging/running). Women's body mass index decreased with walking 4 or more hours per week and with regular alcohol intake, but these behaviors had a smaller effect on men's body mass index. weight gain was inversely associated with high vegetable consumption, walking 4 or more hours per week, and jogging/running 1 to 3 hours per week but not with less demanding physical activities. CONCLUSIONS: Simple derivation of behaviors associated with weight loss or reduced abdominal obesity may enhance programs designed to prevent obesity and chronic diseases.
Adult↗
Cancer, environmental health, and birth defects--examples of new directions in public health practice.
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Congenital Abnormalities↗
Diethylstilbestrol and risk of fatal breast cancer in a prospective cohort of US women.
The authors examined the association between the use of diethylstilbestrol during pregnancy and the risk of subsequent fatal breast cancer in a large prospective study of US adults. After 9 years of follow-up, 1,574 cases of fatal breast cancer were observed among 501,536 gravid women who reported no prior history of cancer in 1982. Results from Cox proportional hazards models showed a positive association between a history of diethylstilbestrol exposure (reported by 3.9% of all women) and fatal breast cancer (adjusted rate ratio = 1.34, 95% confidence interval 1.06-1.69). This excess risk did not increase over time; women who were exposed more than 35 years ago (rate ratio = 1.35, 95% confidence interval 0.97-1.87) were not at greater risk than women who were exposed within the past 35 years (rate ratio = 1.39, 95% confidence interval 1.01-1.93). The positive association was not observed in women who used diethylstilbestrol before age 25 years but was seen at all other ages. The age of study participants did not modify the association between exposure and breast cancer, and there were no significant interactions between ever use of diethylstilbestrol and any of the other potential risk factors included in the analysis. These findings are consistent with those of several other studies of diethylstilbestrol exposure and breast cancer.
Adult↗
Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States.
This study examines the relationship between fatal breast cancer and use of estrogen replacement therapy (ERT) among women in a large prospective study in the United States. After nine years of follow-up, 1,469 breast cancer deaths were observed in a cohort of 422,373 postmenopausal women who were cancer free at study entry and who supplied information on estrogen use. Results from Cox proportional hazards modeling, adjusted for 11 other potential risk factors, showed that ever-use of ERT was associated with a significantly decreased risk of fatal breast cancer (rate ratio [RR] = 0.84, 95 percent confidence interval [CI] = 0.75-0.94). There was a moderate trend (P = 0.07) of decreasing risk with younger age at first use of ERT. This decreased risk was most pronounced in women who experienced natural menopause before the age of 40 years (RR = 0.59, CI = 0.40-0.87). There was no discernible trend of increasing risk with duration of use in estrogen users at baseline or former users, nor was there any trend in years since last use in former users. The relationship between ERT and breast cancer mortality differed by age at menarche and by a self-reported history of breast cysts. No increased risk of fatal breast cancer with ERT was observed with estrogen use status (baseline/former), age at first use, duration of use, or years since last use. These findings suggest that ever-use of ERT is associated with a 16 percent decreased risk of fatal breast cancer.
Adult↗
Investigating causation in cancer clusters.
Questions concerning clusters of cancer cases frequently arise in public health practice. The process of investigating any such cluster requires awareness that such case groupings can easily occur by chance and that any search for biologically meaningful causes will be severely constrained by various methodologic difficulties. These include (1) the long and probably variable latent periods between causative events and cancer diagnosis, (2) the limited numbers of cases available for study in any given cluster situation, and (3) the clinical non-specificity of cancer cases whereby no readily available means are at hand to identify the specific causes for any particular case. Evaluation of any given cluster should involve careful consideration of such limitations, together with a preliminary assessment of the specific cases involved and their community or workplace setting, before more intensive study is undertaken.
Cluster Analysis↗
Cancer prevention in the dental practice: oral cancer screening and tobacco cessation advice.
OBJECTIVES: In this paper we describe the proportion of US adults who report receiving oral cancer screening and tobacco cessation counseling and assistance from dentists and other health professionals. METHODS: Data from the 1992 National Health Interview Survey (NHIS) Cancer Control Supplement, a nationally representative sample of 12,035 adults 18 years of age and older, are analyzed. RESULTS: In 1992, less than 10 percent of adults reported oral cancer screening by a dentist or hygienist within the past three years. White adults (10.1%, 95% CI = 9.3, 10.9) reported an oral cancer screening three times more frequently than black (3.2%, 95% CI = 1.9, 4.5) or Hispanic (3.4%, 95% CI = 2.1, 4.7) adults. About half of adult current smokers had seen a dentist within 12 months, and of those only 24.1 percent (95% CI = 21.7, 26.5) had been advised to quit smoking. Heavy smokers (two or more packs a day) were more likely to have been advised to quit than light (pack or less per day) or occasional smokers. A similar proportion (24.3%, 95% CI = 17.6, 31.0) of white adult men who reported using smokeless tobacco products had been told by a dentist to quit using tobacco. CONCLUSIONS: Results from this population-based survey indicate that cancer screening and tobacco cessation advice are underutilized in the dental practice. Increased patient awareness and implementation of screening and tobacco cessation interventions could improve oral cancer incidence and mortality and have a public health benefit for other tobacco-related morbidity and mortality as well.
Adolescent↗
Estrogen replacement therapy and fatal ovarian cancer.
The authors examined the relation between use of estrogen replacement therapy and ovarian cancer mortality in a large prospective mortality study of 240,073 peri- and postmenopausal women, none of whom had a prior history of cancer, hysterectomy, or ovarian surgery at enrollment in 1982. During 7 years of follow-up, 436 deaths from ovarian cancer occurred. Cox proportional hazard regression was used to adjust for other risk factors. Ever use of estrogen replacement therapy was associated with a rate ratio for fatal ovarian cancer of 1.15 (95% confidence interval (CI) 0.94-1.42). The mortality rate ratio increased with duration of use prior to entry to this study to 1.40 (95 CI% 0.92-2.11) with 6-10 years of use and 1.71 (95% CI 1.06-2.77) with > or = 11 years of use. The increase in mortality associated with > or = 6 years of use was observed in both current users (rate ratio (RR) = 1.72, 95% CI 1.01-2.90) and former users at study entry (RR = 1.48, 95% CI 0.99-2.22), relative to never users. Risk associated with use was not modified by any of the other risk factors. These data suggest that long-term use of estrogen replacement therapy may increase the risk of fatal ovarian cancer.
Adult↗
Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women.
BACKGROUND: The results of several recent epidemiologic studies suggest that estrogen replacement therapy (ERT) in postmenopausal women may decrease their risk of subsequently developing colon or colorectal cancer. However, the association is not clear, as other similar studies have failed to show this inverse relationship. PURPOSE: The present study attempts a more definitive analysis of the relationship between fatal colon cancer and use of ERT among women in a large prospective study of adults in the United States. METHODS: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II), a prospective mortality study of about 1.2 million American men and women (from all 50 states, the District of Columbia, and Puerto Rico), begun by the American Cancer Society in 1982. The median age of the female CPS-II participants was 56 years in 1982. Vital status was determined through December 31, 1989; 630,585 participants (93.2%) were still alive and 43,862 (6.5%) had died after 7 years of follow-up. Death certificates were obtained for 96.2% of participants known to have died. At the end of follow-up, 897 colon cancer deaths were observed in a cohort of 422,373 postmenopausal women who were cancer free at study entry. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors. The likelihood ratio test (two-sided) was used to determine the statistical significance of the interaction terms. RESULTS: Ever use of ERT was associated with significantly decreased risk of fatal colon cancer (RR = 0.71; 95% confidence interval [CI] = 0.61-0.83). The reduction in risk was strongest among current users (RR = 0.55; 95% CI = 0.40-0.76), and there was a significant (P = .0001) trend of decreasing risk with increasing years of use among all users: Users of 1 year or less had an RR of 0.81 (95% CI = 0.63-1.03), while users of 11 years or more had an RR of 0.54 (95% CI = 0.39-0.76). These associations were not altered in multivariate analyses controlling for other risk factors. CONCLUSIONS: In our data, estrogen therapy, particularly recent and long-term use, was associated with a substantial decrease in risk of fatal colon cancer. These results were consistent with several published studies suggesting a protective role of exogenous estrogens in the development of colorectal cancer and merit further investigation.
Aged↗