Evidence of a genetic link between endometriosis and ovarian cancer

Abstract

Objective: To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer.

Design: Pooled genetic analysis.

Setting: University hospital.

Patient(s): Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies.

Intervention(s): None.

Main outcome measure(s): Endometriosis-associated genetic variation and ovarian cancer.

Result(s): There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected.

Conclusion(s): By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.

Keywords: Endometriosis; SNPs; genetic variation; ovarian cancer.

Figure 1. Manhattan and linkage disequilibrium plots for Region P

These plots depict the results for all 184 SNPs in Region P (chromosome 9p21, position 22140648 – 22201586). The Manhattan plot includes ovarian cancer overall (“invasive”) and its four histotypes, with the x-axis corresponding to the chromosomal position (in Mb), the y-axis to the –log P, and the line to P=5.0 × 10⁻⁸. Rs1333052, the most significant SNP in the region (P=2.5 × 10⁻⁴ for ovarian cancer overall), is indicated. The linkage disequilibrium plot depicts pairwise correlation data from the 1000 Genomes CEU population. Epigenomic data from the ENCODE and Roadmap Epigenomics Consortia were obtained and visualized in the UCSC Genome Browser.