Background: While extant research has shown that physical activity increases survival, improves quality of life, and reduces chemotherapy-related adverse effects, previous literature on physical activity and ovarian cancer has been inconsistent. In this dissertation, the association between physical inactivity and the risk of developing invasive EOC was evaluated in distinct subgroups: highly fatal invasive EOC and women aged 75 or above, and younger women aged younger than 45, diagnosed with invasive Epithelial Ovarian Cancer (EOC). This dissertation also included an evaluation of physical inactivity’s influence on the CD8+ TILs expression level among women who participated in both the Ovarian Cancer Consortium Association (OCAC) and Ovarian Tissue Tumor Analysis Consortium (OTTA). Methods: Data from several case-control studies that participated in OCAC were pooled, in order to provide information on the relationship between physical inactivity and invasive EOC risk in distinct subgroups. To assess the risk of developing highly fatal invasive EOC, the first study compared 300 women who died within 12 months after receiving their diagnosis, matched on the basis of age and study site, to 1,216 controls. And 453 cases matched to age and study site were compared to 681 controls; 822 older women with invasive EOC were matched on age and study site to 1,189 controls for the second study. These populations’ risk of developing invasive EOC was assessed using a pooled analytic technique, in which multivariable logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). To evaluate the influence of prediagnostic physical inactivity on the CD8+ TILs expression level, Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% CIs for the last study in this dissertation. Results: The results indicate a statistically significant elevation in the risk of developing both highly fatal invasive EOC and EOC in older women aged 75 or above, compared to physically active women. Also, the results show an increased mortality risk among physically inactive women with negative CD8+ TILs upon primary debulking surgery. The elevation in the mortality rates increased as the level of CD8+ TILs expression decreased, showing a dose-response relationship, observed from low to moderate CD8+ TILs expression. Conclusion: This dissertation’s findings suggest that not engaging in a regular recreational physical activity is associated with increased risk of distinctive EOC subgroup. The results indicate a strong relationship between physical inactivity and developing a highly fatal type of invasive EOC. Further, physical inactivity increases the risk of invasive EOC among women aged 75 or above. The observations for this age group are more distinct than those observed among the general population of EOC patients. Further, a similar pattern occurred for the distributions of the CD8+ TILs among active versus inactive groups, but there was a profound elevation in the mortality risk among inactive women. Consequently, our observations suggest that physical activity status may play a role in CD8+ TILs activation. Further research is needed at the mechanistic level to evaluate the effect of physical inactivity on the immune systems of EOC patients.
|Commitee:||Buas, Matt, O’Connor, Richard, Cannioto, Rikki|
|School:||State University of New York at Buffalo|
|Department:||Roswell Park . Cancer Sciences|
|School Location:||United States -- New York|
|Source:||DAI-B 82/3(E), Dissertation Abstracts International|
|Subjects:||Epidemiology, Oncology, Immunology|
|Keywords:||Physical inactivity, Cancer risk, Survival , Unique ovarian cancer subgroups|
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