ObjectiveBlood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited.MethodsWe conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis.ResultsABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60–0.93) or all non-A (HR: 0.77, 95% CI: 0.63–0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25–0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39–0.99) in unadjusted models.ConclusionsBlood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.

INTRODUCTION: In addition to a fundamental role in transfusion, blood type is also implicated in disease. Blood type antigens on red blood cells are determined by genetic variants in the ABO gene; both phenotype and genotype have been significantly associated with ovarian cancer risk. Meta–analysis of eight case–control studies indicated that women with genetic variants corresponding to blood type A had 9% greater ovarian cancer risk than women with variants corresponding to blood type O. Only one study to date has evaluated ovarian cancer prognosis; among 256 Chinese women, cases with blood type A had more than two–fold worse survival than cases with other blood types (B, AB, and O). AIMS: To evaluate blood type phenotype and genotype in relation to overall ovarian cancer survival in a predominantly Caucasian study population. APPROACH: Tumor registry confirmed ovarian or fallopian tube primary malignancies were identified from the Synthetic Derivative, a de–identified mirror of electronic medical records (EMR) from the Vanderbilt University Medical Center (VUMC). Blood type was ascertained from EMR linked laboratory reports. Ten common variants (minor allele frequency ≥0.05) in the ABO gene were ascertained using the Illumina Exome BeadChip. Subject vital status was determined from EMR and linkage to the National Death Index. Associations with overall survival were evaluated with proportional hazards regression in multivariable models that included adjustment for age, stage, grade, histologic subtype of disease, and year of diagnosis. RESULTS: Blood type phenotype and genotype were available for 556 and 154 tumor registry confirmed ovarian cancer cases, respectively. Among all women, cases with blood type A had significantly better overall survival compared to either blood type O (Hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.63–0.99) or to cases with any blood type other than A (HR: 0.80, 95% CI: 0.65–0.98). A missense variant in exon 7 (rs1053878) with moderate linkage to a variant corresponding to the A phenotype was also associated with better overall survival in a dominant manner (HR: 0.50, 95% CI: 0.25–0.99). While our phenotype association differed by race (p–interaction=0.049) and was evident only among Caucasian cases (HR: 0.75, 95% CI: 0.60–0.93), our genotype association did not vary by race (p–interaction=0.279). CONCLUSIONS: Women with blood type A had better overall ovarian cancer survival, regardless of whether blood type was directly assayed, or inferred by genotype. These findings contradict the only existing ovarian cancer survival study to date, but include a larger, and predominantly Caucasian study population. Additional research is needed to either replicate or refute our ovarian cancer survival finding, and to determine if ABO variants and blood type are causally related to cancer development and progression. Citation Format: Hilary Toole, Rebecca T. Levinson, Gabriella D. Cozzi, Angie Deng, Jason T. Fromal, Malcolm–Robert Snyder, Dineo Khabele, Alicia Beeghly–Fadiel . BLOOD TYPE, ABO GENETIC VARIANTS, AND OVARIAN CANCER SURVIVAL [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-046.