Use of Twins as Mutual Proxy Respondents in a Case-Control Study of Breast Cancer: Effect of Item Nonresponse and Misclassification 

American Journal of Epidemiology Vol. 152, No. 11 : 1093-1103 1dec00

Ann S. Hamilton and Thomas M. Mack

From the Department of Preventive Medicine, Keck School of Medicine at the University of Southern California, Los Angeles, CA.

Full Article

A case-control study of breast cancer in twins diagnosed before 1988 was used to characterize the effects on odds ratios when proxy responses from co-twins are used. North American disease-discordant pairs were ascertained through advertisements, and mailed questionnaires were returned from both members of 671 pairs and from one member of 391 pairs. Biases from the proxy response were attributed to nonresponse or misclassification. Nonresponse varied according to type of exposure variable, depth of detail requested, joint exposure status of the pair, respondent's case-control status, zygosity, and social closeness of the pair. Misclassification was minimal, generally nondifferential, and a high degree of reliability between the proxy and self-report was indicated by the kappa statistic and the intraclass correlation coefficient. By using double-respondent pairs, a method was developed to adjust proxy responses for both sources of bias. These adjustments resulted in minor changes to the odds ratios for the variables studied (age at menarche, reproductive factors, and hormone use). A larger difference was observed between the odds ratios based on all pairs and those based on double-respondent pairs only. These findings demonstrate that, for these variables in this population, twins are reliable proxies for each other and that results from single-respondent pairs should be included.

Key Words: breast neoplasms • case-control studies • proxy • reproducibility of results • twins

Abbreviations: ERT, estrogen replacement therapy • FFTP, first full-term pregnancy • ICC, intraclass correlation coefficient • OR_{all pairs}, odds ratio for all twin pairs • OR_proxy(0), odds ratio based on self-report from the case versus her proxy report about her co-twin • OR_proxy(1), odds ratio based on self-report from the control versus her proxy report about her co-twin • OR_self, odds ratio based on self-report from the case versus self-report from the control • OR_self(0), odds ratio based on self-report from the subset of pairs in which the case provided proxy information about the control • OR_self(1), odds ratio based on self-report from the subset of pairs in which the control provided proxy information about the case.