Association Between Pre-diagnostic Dietary Supplements Intake and Ovarian Cancer Survival: Findings From a Prospective Cohort Study in Chinese Women

Background: As a result of a limited number of studies and inconsistent findings, there remains uncertainty in whether pre-diagnostic dietary supplements intake affects survival after ovarian cancer (OC) diagnosis.Methods: The association between pre-diagnostic dietary supplements intake and all-cause OC mortality was examined in the OC follow-up study, which included a hospital-based cohort (n = 703) of Chinese women diagnosed with OC between 2015 and 2020. Pre-diagnostic dietary supplements information was collected using self-administered questionnaires. Deaths were ascertained up to March 31, 2021, via death registry linkage. Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the aforementioned association.Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7–50.2 months). We found no evidence that any pre-diagnostic dietary supplements intake compared with never is associated with OC survival (HR = 0.75, 95%CI: 0.47–1.18). Furthermore, our study suggested no association for ever supplements intakes of vitamin A (HR = 0.48, 95%CI: 0.07–3.46), vitamin C (HR = 0.64, 95%CI: 0.27–1.54), vitamin D (HR = 1.19, 95%CI: 0.28–5.03), vitamin E (HR = 0.47, 95%CI: 0.06–3.87), multivitamin (HR = 0.49, 95%CI: 0.14–1.67), calcium (HR = 0.96, 95%CI: 0.53–1.72), and fish oil/DHA (HR = 0.31, 95%CI: 0.04–2.37) with OC survival. Interestingly, we only found a detrimental effect of vitamin B supplementation intake (HR = 3.78, 95%CI: 1.33–0.69) on OC survival.Conclusions: We found no evidence that any pre-diagnostic dietary supplements intake is associated with OC survival. Considering lower exposure of dietary supplements before OC diagnosis in the present study, further studies are warranted to confirm these findings.

Genome-wide association and functional interrogation identified a variant at 3p26.1 modulating ovarian cancer survival among Chinese women

Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (Pcombined = 8.90 × 10−10). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.

1466Vitamin D status before, during and after treatment and ovarian cancer survival

Background Previous work found higher serum 25-hydroxyvitamin D (25(OH)D) [circulating form of vitamin D] concentrations at diagnosis were associated with longer survival in patients with ovarian cancer (OvCa). There was no evidence for an association with 25(OH)D after primary treatment, but power was limited. Our aim was to reassess this association in a larger sample, including measures collected during treatment and using techniques to deseasonalise 25(OH)D. Methods Participants were diagnosed between 2002-2006 and 2012-2015 from the Australian Ovarian Cancer Study (AOCS) and the Ovarian Cancer, Prognosis and Lifestyle (OPAL) study, respectively. 25(OH)D concentrations were available for 676 at diagnosis (AOCS), 805 during treatment (AOCS:208; OPAL:597) and 861 after completion of primary treatment and before recurrence (AOCS:342; OPAL:519); 1006 AOCS samples were included in the previous analysis. Sociodemographic, diet and lifestyle data came from questionnaires self-completed at recruitment, and clinical/survival data from medical records, supplemented with National Death Index linkage. We will use Cox regression and non-parametric models to examine associations with survival. Results Median 25(OH)D concentrations were lowest during treatment, intermediate at diagnosis and highest after treatment (AOCS 51, 64, and 71 nmol/L, respectively). 5-year survival was 50% in AOCS and 59% in OPAL. Updated survival results will be presented. Conclusions If the association is confirmed in this updated analysis, then increasing vitamin D concentrations may provide a way to improve survival following OvCa. Key messages Higher circulating vitamin D concentrations may improve survival in OvCa.