| Many researchers are investigating modifiers that could cause the variation in cancer risks that are observed in BRCA1 and BRCA2 mutation carriers. This thesis was an exploratory study to investigate whether there were differences in cancer risks in female offspring depending on whether the BRCA1 or BRCA2 mutation was inherited from the mother or the father. Research shows that BRCA1 affects more molecular pathways than BRCA2. We hypothesized that BRCA1 mutation carriers would be more likely to show significant evidence of a parental origin effect. We hypothesized that due to a female's haplo-insufficiency, her offspring would have an altered in utero exposure that would increase the cancer risk associated with her offspring's inherited BRCA1 mutation.;300 females and 184 females with BRCA1 and BRCA2 mutations, respectively, and an identifiable parent of origin were analyzed using Pearson chi-square, two-sample t-tests and Kaplan-Meier survival curves. The majority of cancers were breast cancers. No parental origin effect was observed in BRCA1 mutation carriers (p-values from 0.414 to 0.768). For BRCA2 mutation carriers, the range of hazard ratios was 1.32 [95% Confidence Interval (CI) of 0.85-2.07] for breast cancer only, 1.42 (95% CI of 0.94-2.15) for breast or ovarian cancer, 1.43 (95% CI of 0.96-2.13) for all cancers, and 2.31 (95% CI of 0.74-7.23) for ovarian cancer only in our larger study sample, showing that inheriting the mutation from their fathers increases women's cancer risks. Additional studies with larger sample sizes and adjusting for other confounders, such as preventative cancer treatments, are needed. |
