Statistical models for analysis of cytogenetic biomarkers

Background: Bleomycin-induced chromosomal breaks (CB) and sister chromatid exchange (SCE) in peripheral blood lymphocytes have been shown to be sensit ive cytological markers for susceptibility to DNA damage in patients with v arious types of cancer and in healthy controls. Factors such as age, sex, s moking, and alcohol consumption could affect the values of some of these bi omarkers and should be considered as covariates when analyzing cytogenetic biomarkers because these factors can affect the frequency of CB and SCE. Methods: We propose a statistical method using negative binomial (NB) distr ibution to evaluate the numbers of CB and SCE. In order to determine the be st model to represent the frequency of CB and SCE, we compared the NE model with the widely used Poisson model and log-transformed normal model by usi ng generalized linear models. To demonstrate the better fit of the NE model , we analyzed three different data sets from studies conducted at The Unive rsity of Texas M.D. Anderson Cancer Center. The first set was a case-contro l study of lung cancer in a population of African Americans and Mexican Ame ricans (286 cases and 156 controls), the second set consisted of 311 head a nd neck cancer patients, and the third set consisted of 105 Hodgkin's disea se patients. Results: For CB, the estimates of the variability for Hodgkin's disease, he ad and neck, and lung cancers were 487.24, 502.82, and 520.15, respectively . For SCE, the estimates of the variability for Hodgkin's disease was 9777. 01. For CB, the dispersion estimates under the three models (Poisson, NE, a nd Normal) for Hodgkin's disease, head and neck, and lung cancers were: 12. 30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively. For SCE (Hodgkin's disease only), the dispersion estimates under the three mode ls (Poisson, Nh, and Normal) were 30.91, 1.11, 0.10, respectively. Conclusions: Our results demonstrate that the NE model provides a better in terpretation and fit for the frequency of CB and SCE in different cancer ty pes. Therefore, we recommend it as a model for the analysis of cytogenetic biomarkers.