Analysis of common variations in tumor-suppressor genes on chr1p36 among Caucasian women with endometriosis

ObjectiveEpidemiological data indicate that endometriosis increases the risk of epithelial ovarian cancer (EOC), but the mechanism of cancer transition is unknown. Results from genome-wide association studies (GWAS) and transcriptome sequencing have demonstrated that genes located in the 1p36 region are important in both endometriosis and endometriosis-associated cancer development. Therefore, we tested the hypothesis that SNPs in two tumor-suppressor genes (CHD5 and ARID1A) in the 1p36 region are associated with endometriosis.MethodsAllele frequencies of SNPs were investigated in 1685 Caucasian women consisting of 947 women with endometriosis and 738 controls. Peripheral blood samples were retrieved, DNA extracted and allelic frequencies of SNPs in two tumor-suppressor genes (CHD5 and ARID1A) were analyzed using TaqMan Open Array technique.ResultsAssociations were observed for 3 SNPs in the CHD5 gene: rs1883603 (OR 1.31, 95% CI 1.00–1.71), rs9434741 (OR 1.41, 95% CI 1.16–1.71) and rs17436816 (OR 1.24, 95% CI 1.02–1.50). After correction for multiple comparisons, rs9434741 (CHD5) remained significantly associated with endometriosis (p < 0.01). No associations were detected for ARID1A.ConclusionsIn this Caucasian population, endometriosis seems to be associated with the tumor-suppressor gene CHD5. Our findings support recent data, suggesting that the 1p36 region plays an important role in endometrios. To validate these data, replication in an independent population is warranted.

► Endometriosis-associated ovarian cancer is associated with mutations in the chr. 1p36 region.
► Analysis of common genetic variants in two chr. 1p36 genes demonstrates an association between endometriosis and the tumor-suppressor CHD5.
► Genetic changes in the 1p36 region may play an important role in the transformation of endometriosis into ovarian cancer.