Biomedical subjects

S Wacholder

Publications and source records attributed to S Wacholder.

At least 91 records · Page 5Linked to original sources

PubMed1994

Gender differences in hematopoietic and lymphoproliferative disorders and other cancer risks by major occupational group among workers exposed to benzene in China.

Gender differences in risk for leukemia and other selected and combined disease categories were examined by major occupational category for 74,828 benzene-exposed workers compared to 35,805 unexposed workers from 12 cities in China. No significant differences in the relative risks for total mortality and cancer mortality were found between female and male benzene-exposed workers, although risks tended to be somewhat higher among male than among female employees. Both female and male workers in several occupational categories had notably increased risks for all hematopoietic and lymphoproliferative (HLP) malignant and nonmalignant disorders combined and for total leukemia. Variation in risk for HLP disorders by occupational category was observed in both genders, with highest risks for male and female chemical manufacturing workers, female nonproduction employees, and male printers. However, the numbers of leukemia and other HLP malignancies in each category were small. The findings suggest that both female and male benzene-exposed workers in several occupational categories experience excess leukemia and other HLP disorders with relatively minor gender differences. Although this population is one of the largest cohorts of benzene-exposed workers studied to date, evaluation of the observed variation in risk for HLP neoplasms among the occupational groups for workers of each gender is limited by the small numbers of these relatively rare malignancies.

Benzene↗

PubMed1994

Flexible maximum likelihood methods for assessing joint effects in case-control studies with complex sampling.

Case-control studies can often be made more efficient by using frequency matching, randomized recruitment, stratified sampling, or two-stage sampling. These designs share two common features: (1) some "first-stage" variables are ascertained for all study subjects, while complete variable ascertainment is carried out for only a selected subsample, and (2) the subsampling of subjects for "second-stage" variable ascertainment depends jointly on their disease status and their observed first-stage variables. Because first-stage variables alter the subsampling fractions, standard analyses require a multiplicative specification of any joint effects of a second- and a first-stage variable. We show that by making use of missing data methods, maximum likelihood estimates can be obtained for risk parameters of interest, even those characterizing interactions between first- and second-stage variables. Joint effects can thus be modelled flexibly, with allowance for both additive and multiplicative models. Preliminary data from a case-control study of lung cancer as related to age, sex, and smoking provide an example, leading to the suggestion that the combined effect of age and smoking is multiplicative.

Adult↗

PubMed1993

Second cancers among long-term survivors of non-Hodgkin's lymphoma.

BACKGROUND: Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for second cancers. Few studies, however, include long-term survivors, and none report risk for second cancer among NHL patients surviving 15 or more years. PURPOSE: Our aim was to examine the pattern of second cancers among long-term survivors of NHL. METHODS: A cohort of 6171 patients diagnosed with NHL as a first primary cancer and who survived 2 or more years was identified within population-based tumor registries in Sweden, Ontario, and Iowa and within the affiliated tumor registry of The Netherlands Cancer Institute. Nearly 1000 NHL patients lived 15 or more years after diagnosis. Tumor registry files were searched for new invasive primary malignancies. RESULTS: Second cancers were reported in 541 subjects (observed-to-expected ratio [O/E] = 1.37; 95% confidence interval = 1.26-1.49), with significant excesses seen for all solid tumors (O/E = 1.28), acute nonlymphocytic leukemia (O/E = 4.83), melanoma (O/E = 2.38), Hodgkin's disease (O/E = 12.0), and cancers of the lung (O/E = 1.36), brain (O/E = 2.33), kidney (O/E = 2.07), and bladder (O/E = 1.77). Among 15-year survivors, significantly increased risks persisted for all second cancers (O/E = 1.45), solid tumors (O/E = 1.37), bladder cancer (O/E = 3.24), and Hodgkin's disease (O/E = 25.0). The actuarial risk of developing a second cancer 3-20 years after diagnosis of NHL was 21%, compared with a population expected cumulative risk of 15%. CONCLUSIONS: Patients with NHL continue to be at significantly elevated risk of second primary cancer for up to two decades following diagnosis. The pattern of risk suggests the influence of treatment as well as factors associated with the underlying disease. IMPLICATIONS: Quantitative studies of second cancer following NHL are needed to clarify the role of antecedent therapy, shared risk factors, host susceptibility, and other etiologic and diagnostic influences. Despite the generally advanced age of patients with NHL, the persistently elevated risk of second cancers should alert clinicians to the importance of continued medical surveillance.

Adolescent↗

PubMed1993

Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia.

BACKGROUND: Experimental studies have provided strong evidence that human papillomavirus (HPV) is the long-sought venereal cause of cervical neoplasia, but the epidemiologic evidence has been inconsistent. PURPOSE: Given improvements in HPV testing that have revealed a strong link between sexual activity history and cervical HPV infection, we conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection. METHODS: We studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente, a large prepaid health plan, in Portland, Ore. The established epidemiologic risk factors for CIN were assessed by telephone interview. We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV. RESULTS: The case subjects demonstrated the typical epidemiologic profile of CIN: They had more sex partners, more cigarette smoking, earlier ages at first sexual intercourse, and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. Seventy-six percent of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account, an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women. CONCLUSION: The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV. IMPLICATIONS: In light of this conclusion, the investigation of the natural history of HPV has preventive as well as etiologic importance.

Adolescent↗

PubMed1993

Interpretation of energy adjustment models for nutritional epidemiology.

The authors discuss the interpretation of three alternative energy adjustment models for nutritional epidemiology. It is shown that four different effects are addressed by these models: 1) adding nutrient N, 2) substituting nutrient N for "other" nutrients, 3) adding "other" nutrients, and 4) adding both N and "other" nutrients in a specific ratio. Each of these effects may be estimated from any of the three models. The relative standard errors for the four estimated effects are also provided.

Diet↗

PubMed1993

Validation studies using an alloyed gold standard.

A key assumption made when using a validation study to correct an estimate of relative risk for bias due to misclassification or measurement error is that the available measure, known to have error but nonetheless used routinely in the main study, is compared to a gold standard measured without error. In most epidemiologic applications, the putative gold standard is in fact measured with error. The effect of the violation of the assumption on the corrected estimate depends on the magnitudes of the errors in the two measures and on their correlation. In particular, when the errors are negatively correlated, independent, or weakly positively correlated, the corrected estimate will tend to overcorrect beyond the true value.

Bias↗

PubMed1993

A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States).

Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy.

Adult↗

PubMed1992

Selection of controls in case-control studies. I. Principles.

A synthesis of classical and recent thinking on the issues involved in selecting controls for case-control studies is presented in this and two companion papers (S. Wacholder et al. Am J Epidemiol 1992;135:1029-50). In this paper, a theoretical framework for selecting controls in case-control studies is developed. Three principles of comparability are described: 1) study base, that all comparisons be made within the study base; 2) deconfounding, that comparisons of the effects of the levels of exposure on disease risk not be distorted by the effects of other factors; and 3) comparable accuracy, that any errors in measurement of exposure be nondifferential between cases and controls. These principles, if adhered to in a study, can reduce selection, confounding, and information bias, respectively. The principles, however, are constrained by an additional efficiency principle regarding resources and time. Most problems and controversies in control selection reflect trade-offs among these four principles.

Case-Control Studies↗

PubMed1992

Selection of controls in case-control studies. II. Types of controls.

Types of control groups are evaluated using the principles described in paper 1 of the series, "Selection of Controls in Case-Control Studies" (S. Wacholder et al. Am J Epidemiol 1992;135:1019-28). Advantages and disadvantages of population controls, neighborhood controls, hospital or registry controls, medical practice controls, friend controls, and relative controls are considered. Problems with the use of decreased controls and proxy respondents are discussed.

Case-Control Studies↗

PubMed1992

Selection of controls in case-control studies. III. Design options.

Several design options available in the planning stage of case-control studies are examined. Topics covered include matching, control/case ratio, choice of nested case-control or case-cohort design, two-stage sampling, and other methods that can be used for control selection. The effect of potential problems in obtaining comparable accuracy of exposure is also examined. A discussion of the difficulty in meeting the principles of study base, deconfounding, and comparable accuracy (S. Wacholder et al. Am J Epidemiol 1992;135:1019-28) in a single study completes this series of papers.

Bias↗

PubMed1992

Oral contraceptives and primary liver cancer among young women.

The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR] = 1.6, 95 percent confidence interval [CI] = 0.9-2.6), and for long-term (greater than or equal to 10 years) users (OR = 2.0, CI = 0.8-4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR = 2.7, CI = 1.4-5.3) and long-term users (OR = 4.8, CI = 1.7-14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.

Adult↗

PubMed1992

A cohort study of tobacco use, diet, occupation, and lung cancer mortality.

In 1966, a cohort of White males aged 35 or over, who were policy-holders with the Lutheran Brotherhood Insurance Society (United States), completed a mail questionnaire on tobacco use, diet, and demographic characteristics. During the 20 years of follow-up, 219 lung cancer deaths occurred. Besides the strong relationship with cigarette smoking, we observed an effect on lung cancer risk among current users of cigars or pipes who were nonsmokers of cigarettes (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 1.0-12.6) or who were past/occasional users of cigarettes (RR = 2.7, CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were found among craftsmen and laborers, with the highest risks among subjects who worked in the mining or manufacturing industry. No association between current (as of 1966) use of beer or hard liquor and lung cancer was observed, although past users were at elevated risk. An inverse association between lung cancer and intake of fruits was observed, and risks of lung cancer were lower among persons in the highest dietary intake quintiles of vitamins A and C. Except for oranges, however, none of the inverse associations with fruits or dietary nutrients had statistically significant trends. The findings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possibly protective effect of dietary factors on lung cancer risk.

Ascorbic Acid↗

PubMed1992

Occupational physical activity and colon cancer risk in Turkey.

A case-control study of 107 colon cancer cases and 486 controls from an oncological clinic in Istanbul was conducted to examine the association between occupational physical activity and colon cancer in Turkey, where incidence of this disease is low. Only two of the four activity measures showed evidence of an increased colon cancer risk for sedentary jobs (time spent sitting OR = 1.5 and occupational energy expenditure OR = 1.6); neither was statistically significant. Subjects below age 55 showed higher risk associated with sedentary jobs than did the older age group, probably due to their adoption of a more western lifestyle, including dietary habits, less activity, and other factors that may interact to increase the risk of colon cancer.

Adolescent↗

PubMed1992

The Bethesda System. A proposal for reporting abnormal cervical smears based on the reproducibility of cytopathologic diagnoses.

In the Bethesda System, noninvasive squamous abnormalities are classified as atypical squamous cells of undetermined significance (ASQUS), low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions. The Bethesda System eliminates two diagnostic distinctions that are made in the dysplasia/carcinoma in situ and cervical intraepithelial neoplasia (CIN) classifications, CIN1 vs koilocytotic atypia and CIN2 vs CIN3, and maintains three others, negative vs ASQUS, ASQUS vs koilocytotic atypia, and CIN1 vs CIN2. To determine whether the diagnostic distinctions preserved in the Bethesda System are made more consistently than those eliminated, we analyzed the interobserver reproducibility of two cytopathologists in classifying 257 smears. The findings indicate that the distinctions retained in the Bethesda System are more reproducible than those eliminated. Specifically, cases classified as koilocytotic atypia were distinguished from CIN1 no more reproducibly than predicted by chance, whereas CIN2 and CIN3 were distinguished as consistently as any other pair of diagnoses examined. In 13 cases in which there was interobserver discordance, one reviewer classified the smear as ASQUS and the other reviewer diagnosed CIN2 or CIN3. The findings in this study suggest that smears showing koilocytotic atypia and/or CIN1 may be reported as low-grade squamous intraepithelial lesions without further specification. In contrast, smears showing high-grade squamous intraepithelial lesions may be further classified as CIN2 or CIN3 in accordance with the Bethesda guidelines. Since the diagnosis of ASQUS is applied to smears showing a wide spectrum of changes, management of patients with the diagnosis of ASQUS will be facilitated by providing an explanatory note and/or recommendations when appropriate.

Carcinoma in Situ↗

PubMed1991

Blind assignment of exposure does not always prevent differential misclassification.

The authors argue that one can never be certain whether an exposure variable which is measured with error is subject to differential misclassification in either a case-control study or a cohort study. They present hypothetic examples that demonstrate that even when misclassification is nondifferential in a 2 x 3 table, the observed odds ratios in the 2 x 2 table created by collapsing over two exposure levels can be either in the opposite direction from or more extreme than the odds ratio that would be obtained if exposures were classified correctly. The anomalies are explained by the observation that the 2 x 2 tables exhibit differential misclassification. In general, collapsing over categories which have different risks of disease and different probabilities of exposure misclassification can induce differential misclassification and even nonconservative estimates of relative risk. Collapsing of exposure levels can occur in the analysis or at the exposure assessment stage. Since indistinguishable categories can be collapsed implicitly, blind assessment of exposure, i.e., assignment without knowledge of disease status, does not guarantee that misclassification is nondifferential.

Case-Control Studies↗

PubMed1991

A cohort study of stomach cancer in a high-risk American population.

Demographic, smoking and dietary information was obtained from a cohort of 17,633 white American men, largely of Scandinavian and German descent, who responded to a mailed questionnaire in 1966. After 20 years of follow-up, 50% to 90% increases in mortality from stomach cancer (75 deaths) were found among foreign-born, their children, and among residents of the North Central states. An association was seen with low educational attainment and laboring or semiskilled occupations, primarily among immigrants and their children. Risk was evaluated in subjects who regularly smoked cigarettes (RR = 2.6, 95% CI = 1.1 to 5.8). A significant dose-response trend was observed, with subjects who smoked 30 or more cigarettes per day having more than a five-fold increased risk compared with those who never smoked. Elevated risks were also found for pipe smoking and smokeless tobacco use, but not for alcohol consumption. Analysis of dietary consumption of nine food groups revealed no significant associations with stomach cancer. However, total carbohydrate intake and a few individual food items (salted fish, bacon, cooked cereal, milk, and apples) were associated with increased risk. The findings of this prospective study of a high-risk population add to the limited evidence relating tobacco consumption to stomach cancer risk and suggest clues to ethnic, geographic, and dietary risk factors.

Adult↗

PubMed1991

Cigarette smoking and leukemia: results from the Lutheran Brotherhood Cohort Study.

In a 20-year follow-up (1966-86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR] = 2.7), and other and unspecified leukemia (RR = 1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking.

Adult↗

PubMed1991

Bias despite masked assessment of clinical outcomes when an outcome is defined as one of several component events.

Hypothetical examples are presented that show that bias can result from misclassification of clinical outcomes defined as one of several events, even though the assessment of each component event was masked. In one example, the effect of the overall misclassification is to make a treatment that reduces the risk appear to increase it; in another example, misclassification causes the overall treatment effect to appear stronger than it actually is. These anomalies are due to the fact that the misclassification of the overall outcome can be differential, even though the misclassification of the individual components is nondifferential.

Acquired Immunodeficiency Syndrome↗