Date of Conferral





Public Health


Grace Lasker


Ovarian cancer is the deadliest gynecological malignancy affecting women. Diagnosis often occurs late due to non-specific symptoms, but if detected early, there is excellent chance for survival. One of the most important risk factors is family history. Up to 24% of cases are due to inherited loss-of-function mutations in genes involved in the DNA damage response. The theory underlying hereditary cancers is Knudson's two-hit theory of cancer causation, where two hits are necessary for cancer to occur in an individual: one in the germline and one in the tissue. The genes, CHEK1 and CHEK2, are modulators of the DNA damage response, and could be susceptible to a first hit. There is little to no evidence about whether loss-of-function mutations in either of these two genes can lead to ovarian cancer. Using a cohort of 587 ovarian cancer cases and 557 controls, this study sought to determine if CHEK1 and CHEK2 are associated with ovarian cancer. Applying Fisher's exact test to compare mutation rates and the t test to compare age at time of diagnosis, the alternative hypothesis about an association between disease and mutations in CHEK1 and CHEK2 was rejected, but an association between younger age at diagnosis in cases and mutations in either gene was confirmed. The association between age and mutations in either of these genes suggests that there is some influence of age on disease, but a clear association between development of disease and mutations cannot yet be established. This research has implications for social change: By recognizing the need to test earlier in women with mutations in CHEK1 and/or CHEK2, they will have a higher chance of survival and better health outcomes, not only for ovarian cancer but for related cancers as well.