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1. A General formulation for standardization of rates as a method to control confounding by measured and unmeasured disease risk factors

Author

Mark, Steven D.

Subjects
Statistics - Applications
Abstract

Standardization, a common approach for controlling confounding in population-studies or data from disease registries, is defined to be a weighted average of stratum specific rates. Typically, discussions on the construction of a particular standardized rate regard the strata as fixed, and focus on the considerations that affect the specification of weights. Each year the data from the SEER cancer registries are analyzed using a weighting procedure referred to as ``direct standardization for age.'' To evaluate the performance of direct standardization, we define a general class of standardization operators. We regard a particular standardized rate to be the output of an operator and a given data set. Based on the functional form of the operators, we define a subclass of standardization operators that controls for confounding by measured risk factors. Using the fundamental disease probability paradigm for inference, we establish the conclusions that can be drawn from year-to-year contrasts of standardized rates produced by these operators in the presence of unmeasured cancer risk factors. These conclusions take the form of falsifying specific assumptions about the conditional probabilities of disease given all the risk factors (both measured and unmeasured), and the conditional probabilities of the unmeasured risk factors given the measured risk factors. We show the one-to-one correspondence between these falsifications and the inferences made from the contrasts of directly standardized rates reported each year in the Annual Report to the Nation on the Status of Cancer., Comment: Published in at http://dx.doi.org/10.1214/08-AOAS170 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Published
2008
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9. A Pooled Analysis of Thyroid Cancer Studies. V. Anthropometric Factors

Author

Maso, Luigino Dal, La Vecchia, Carlo, Franceschi, Silvia, Preston-Martin, Susan, Ron, Elaine, Levi, Fabio, Mack, Wendy, Mark, Steven D., McTiernan, Anne, Kolonel, Laurence, Mabuchi, Kiyohiko, Jin, Fan, Wingren, Gun, Galanti, Maria Rosaria, Hallquist, Arne, Glattre, Eystein, Lund, Eiliv, Linos, Dimitrios, and Negri, Eva

Published
2000

20. Hepatitis C virus infection, Linxian, China (1)

Author

Zhang, Mingdong, Sun, Xiu-Di, Mark, Steven D., Chen, Wen, Wong, Lara, Dawsey, Sanford M., Qiao, You-Lin, Fraumeni, Joseph F., Jr., Taylor, Philip R., and O'Brien, Thomas R.

Subjects
Blood-borne diseases -- Development and progression, Blood-borne diseases -- Diagnosis, Hepatitis C virus -- Development and progression, Hepatitis C virus -- Diagnosis
Abstract

Bloodborne viruses may have spread in rural China during the past 25 years, but population-based prevalence estimates are lacking. We examined the frequency of hepatitis C virus (HCV) and HIV [...]

Published
2005

22. A pooled analysis of case-control studies of thyroid cancer¶ III. Oral contraceptives, menopausal replacement therapy and other female hormones

Author

Vecchia, Carlo La, Ron, Elaine, Franceschi, Silvia, Maso, Luigino Dal, Mark, Steven D., Chatenoud, Liliane, Braga, Claudia, Preston-Martin, Susan, McTiernan, Anne, Kolonel, Laurence, Mabuchi, Kiyohiko, Jin, Fan, Wingren, Gun, Galanti, Maria Rosaria, Hallquist, Arne, Lund, Eiliv, Levi, Fabio, Linos, Dimitrios, and Negri, Eva

Published
1999
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30. Serum concentrations of 1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) and 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (DDE) and risk of primary liver cancer

Author

McGlynn, Katherine A., Abnet, Christian C., Zhang, Mingdong, Sun, Xiu-Di, Fan, Jin-Hu, O'Brien, Thomas R., Wei, Wen-Qiang, Ortiz-Conde, Betty A., Dawsey, Sanford M., Weber, Jean-Philippe, Taylor, Philip R., Katki, Hormuzd, Mark, Steven D., and Qiao, You-Lin

Subjects
Insecticides -- Influence, Insecticides -- Case studies, Liver tumors -- Causes of, Liver tumors -- Case studies, Health
Abstract

Background: 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) exposure has been demonstrated to cause liver tumors in laboratory rodents. DDT's persistent metabolite and environmental degradation product, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has also been associated with liver tumors in laboratory animals. Whether DDT and DDE are associated with hepatocarcinogenesis in humans is not clear. Methods: We carried out a nested case-control study among the participants of the Nutritional Intervention Trials in Linxian, China. The case group included 168 individuals who developed liver cancer during the trials, and the control group included 385 individuals frequency-matched on age and sex who were alive and well at the end of the study. Serum concentrations of DDT and DDE were measured by gas chromatography--mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable analysis. Results: In multivariable-adjusted models, the risk of developing liver cancer increased with increased serum DDT concentration (OR for quintile 1 versus quintile 5 = 3.8, 95% CI = 1.7 to 8.6, [P.sub.trend] = .0024). In contrast, there was no statistically significant association between liver cancer and serum DDE concentration. The association between high serum DDT concentration and liver cancer was stronger among individuals with DDE concentrations below the median value (odds ratio for tertile 3 versus tertile 1 = 3.55, 95% CI = 1.45 to 8.74) than those with concentrations above the median (OR = 1.70, 95% CI = 0.97 to 2.98). A calculation of crude liver cancer risk found that there would be 26 liver cancers per 100000 persons per year in the lowest quintile of DDT exposure versus 46 liver cancers per 100000 persons per year in the highest quintile of DDT exposure. Conclusions: DDT may be a risk factor for liver cancer, particularly among persons with lower DDE concentrations. Risk may be particularly increased among persons exposed directly to DDT (resulting in a higher ratio of DDT to DDE) or, alternatively, risk may be associated with individual ability to metabolize DDT to DDE.

Published
2006

40. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia

Author

Li Jun-Yao, Taylor, Philip R., Li Bing, Dawsey, Sanford, Wang Guo-Qing, Ershow, Abby G., Guo Wande, Liu Shu-Fan, Yang, Chung S., Shen Qiong, Wang Wen, Mark, Steven D., Zou Xiao-Nong, Greenwald, Peter, Wu Yang-Ping, and Blot, William J.

Subjects
China -- Health aspects, Esophageal cancer -- Prevention, Dietary supplements -- Health aspects, Dysplasia -- Health aspects, Health
Abstract

Background: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia. Purpose: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian. Methods: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years. Results: A total of 324 deaths occurred during the 6-year intervention period: 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P>.10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P>.10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P>.10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P>.10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. Conclusions: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus. Implications. Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia. [J Natl Cancer Inst 85:1492-1498, 1993]

Published
1993

41. Flow cytometric analysis of nuclear DNA content in ovarian tumors: association of ploidy with tumor type, histologic grade, and clinical stage

Author

Lage, Janice M., Weinberg, David S., Huettner, Phyllis C., and Mark, Steven D.

Subjects
Ovarian tumors -- Genetic aspects, Flow cytometry -- Diagnostic use, Ploidy -- Physiological aspects, Ovarian cancer -- Prognosis, DNA -- Measurement, Health
Abstract

The authors undertook a prospective, flow cytometric study of nuclear DNA ploidy in 140 fresh ovarian tumors. There were 43 benign tumors, 27 borderline tumors, and 70 malignant tumors. Results of DNA ploidy analysis were compared to age at diagnosis, menopausal status, tumor size, histologic type, grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Although the majority of benign tumor were diploid, 19% were aneuploid. Among the benign tumors, DNA ploidy was significantly associated with tumor type and tumor size. All borderline tumors were diploid. Of the 70 malignant tumors, 64% were aneuploid. In the malignant tumors, DNA aneuploidy has significant univariate associations with histologic type, grade, and FIGO stage. By multivariate analysis, DNA aneuploidy remained significantly associated with stage and grade, both known predictors of survival in ovarian cancer. These results indicate that DNA ploidy varies with the aggressive potential of an ovarian cancer and may, at the time of initial diagnosis, provide additional information about tumor prognosis. Cancer 1992; 69:2668-2675.

Published
1992

49. Squamous dysplasia is the histologic precursor of invasive esophageal squamous cell carcinoma: results from a 13-year prospective follow-up study in a high-risk population

Author

Wang, Guo-Qing, primary, Abnet, Christian C., additional, Liu, Fu-Sheng, additional, Lewin, Klaus J., additional, Sun, Xiu-Di, additional, Roth, Mark J., additional, Qiao, You-Lin, additional, Mark, Steven D., additional, Fan, Jin-Hu, additional, Taylor, Philip R., additional, Dong, Zhi-Wei, additional, and Dawsey, Sanford M., additional

Published
2003
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