Cell cycle checkpoints play critical roles in the maintenance of genomic integrity and inactivation of checkpoint genes and are frequently perturbed in most cancers. men. When the African American women were categorized into quartiles a significant reverse trend of decreased G2/M checkpoint function and increased lung cancer risk was present with lowest-vs-highest quartile OR of 13.72 (95% CI = 2.30 – 81.92 Ptrend < 0.01). Genotype-phenotype correlation analysis indicated that polymorphisms in and genes were significantly associated with the γ-radiation-induced G2/M arrest phenotype. This study provides evidence that a less efficient G2/M checkpoint is significantly associated with lung BMS-707035 cancer risk in African American women. The data also suggested that the function of G2/M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control. and (cellular response to carcinogen exposure (28;29). Previously we reported our initial findings that less efficient G2/M checkpoint function was associated with an increased risk of lung cancer in African Americans (28). Here we report the final results with a larger sample size (299 cases and 550 controls) and examined genotype-phenotype correlations using a multigenic pathway approach. We seek to test the hypothesis that deficiencies in response to DNA damage-induced cell cycle regulation contribute to the risk of developing lung cancer BMS-707035 and genetic polymorphisms in DNA repair and/or cell BMS-707035 cycle control genes affect G2/M checkpoint function. The study aims are: i) determine the association between γ-radiation-induced G2/M arrest and lung cancer risk; ii) examine the correlations between G2/M arrest phenotype and genetic polymorphisms in DNA repair and cell cycle control genes. Material and Methods Study population The study population accrual and eligibility criteria have been described previously (30). The 299 lung cancer patients were recruited from seven hospitals in the Baltimore Maryland metropolitan area between 1999 and 2004. All cases were histologically confirmed non-small cell lung cancer patients. Population controls (n =322) were recruited from the same Maryland counties of residence as the lung cancer cases by screening information obtained from the Maryland Department of Transportation (MDT) which allowed us to obtain a random sample of controls frequency-matched to the cases by age. African-American population controls were oversampled by design. Hospital controls (N = 228) were cancer-free patients recruited from the same hospital as cases and were frequency-matched to the cases by gender race age and smoking status. The overall participation rates of the study population for eligible subjects were 90% 88 and 88% for cases population- and hospital-controls respectively. Among the BMS-707035 cases the distribution of gender and race was similar between participants and non- participants and among the control groups the distribution of gender was also similar. However African American males were significantly more likely to be non- participants in both population and hospital control groups. Eligibility criteria Eligible subjects had to be either Caucasian or African American free of known diagnosis of HIV HCV and HBV; born in the United States; a resident of Baltimore City or its adjacent counties or counties of the Maryland Eastern Shore; able to speak English well enough to be interviewed; non-institutionalized; and currently not taking antibiotics or immunosuppressive medications (e.g. steroids). Subjects who had undergone surgery provided a blood sample either before the surgery or three months after the surgery. Subjects who had undergone chemotherapy or radiation therapy were excluded from CNOT10 this study. Chemotherapy radiation therapy and active infections are known to affect the growth potential of the lymphocytes and so we excluded such subjects to maximize the validity of the results. The study was approved by the Institutional Review Boards of the National Cancer Institute University of Maryland Baltimore the Johns Hopkins University School of Medicine Sinai Hospital MedStar Research Institute and the Research Ethics Committee of Bon Secours Baltimore Health System. After informed consent was obtained cases and controls received a structured in-person interview assessing prior medical and cancer history tobacco use alcohol use current medications occupational history family medical history reproductive history and estrogen use recent nutritional supplements and caffeine intake and socioeconomic characteristics. Blood was obtained by trained interviewers in.