Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Abstract

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

“…23 Quality control was as per previous work, with related individuals and ancestry outliers removed. 4 We excluded 13 studies of individuals of nonEuropean ancestry 4 ; the remaining studies that contributed to our analysis are listed in Supplementary Table 4 (available as Supplementary data at IJE online). For examination of all histotypes of ovarian cancer combined, we had 10 065 cases and 21 654 controls for analysis.…”

“…2,3 The most common histological subtype is serous carcinoma (further classified into high-grade serous and low-grade serous); other subtypes include mucinous, clear cell and endometrioid carcinomas. 4 Higher parity and oral contraceptive use reduce risk whereas established risk factors include a history of endometriosis, obesity and family history of ovarian or breast cancer. 5 Several recent studies have examined whether or not serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with ovarian cancer risk or mortality.…”

‘Omic’ high-throughput technologies in research on pathogenesis of endometriosis: a Review

“…Исследования по-казали, что эндометриоидные очаги при эндометри-озассоциированном раке яичников проходят много-ступенчатую трансформацию от типичного к ати-пичному эндометриозу, а затем к раку [51]. Относи-тельно частоты некоторые авторы оценивают риск в 1% для развития опухолей из эндометриальной тка-ни [51][52][53].…”

“…Предполагается, что эпигенети-ческие процессы и соматические генетические изме-нения могут инициировать онкогенез [51][52][53]. J. Gogusev и соавт.…”

Complex trait genetics: mapping, correlation and causation

“…One of our previous studies [342] estimated the array heritability (i.e., heritability explained by about 200,000 genotyped SNPs but not all the genome) of all EOC to be 5.6%, and 8.8% for the most common EOC subtype, high-grade serous.…”