Abstract
We evaluated the association of 56 candidate SNPs identified in two published genome-wide association studies (GWAS) of uterine leiomyoma (UL), or fibroids, with the risk and tumor size in the multi-ethnic uterine fibroid study (NIEHS-UFS). The selected SNPs were genotyped in 916 premenopausal women of African American (AA) and European American (EA) descents and their association with the outcomes was evaluated in race-stratified models and in meta-analysis of risk in NIEHS-UFS and discovery and replication GWAS in the Japanese population. We report moderate associations of variant rs4954368 in THSD7B (thrombospondin, type I, domain containing 7B) with tumor size in pooled analysis of AA and EA samples (P = 0.004), and at TNRC6B (trinucleotide repeat containing 6B) variants rs138039 and rs139909 in EA (P = 0.001 and 0.008, respectively). The most significant associations with risk in meta-analysis were observed at TNRC6B variants rs739182 (P = 3.7 × 10−10) and rs2072858 (P = 1.1 × 10−9) and were stronger than those reported in the discovery GWAS (P = 2.01 × 10−8 and 2.58 × 10−8, respectively). The present study failed to replicate the associations reported for CCDC57 and FASN in a discovery GWAS in populations of European descent. Consistent with previous replication studies in the Right From the Start Study (RFTS) and the BioVU DNA repository, we provide independent evidence for association of TNRC6B with both risk and size of UL. The present study is the first to report a replicated association of THSD7B with UL, albeit with tumor size and not with risk.
Highlights
Uterine leiomyoma (UL), or fibroids, are common hormone-dependent tumors that arise in the smooth muscle cells of the uterus
Age, menopause, and African American (AA) ethnicity, which was originally tested in NIEHS-UFS (National Institute of Environmental Health Sciences-Uterine Fibroid Study) (Baird et al, 2003) are established risk factors
Among the 1045 typed samples, 42 (4.0%) with call rates
Summary
Uterine leiomyoma (UL), or fibroids, are common hormone-dependent tumors that arise in the smooth muscle cells of the uterus. No convergent views on a potential mechanism of pathogenesis have emerged from the genome linkage scans and genome-wide association studies (GWAS) reported to date (Gross et al, 2004; Cha et al, 2011; Eggert et al, 2012; Wise et al, 2012) These GWA studies pointed to TNRC6B (trinucleotide repeat containing 6B) and BET1L (Bet golgi vesicular membrane trafficking protein-like) as the most significant candidate genes in the Japanese population (Cha et al, 2011) and to FASN (fatty acid synthase) and the nearby CCDC57 (coiled-coil domain containing 57) gene in the European American population of the WGHS (Women Genome Health study) (Eggert et al, 2012) and Australian populations. We report double-sided pvalues uncorrected for multiple testing from meta-analyses and from race-stratified analyses for the two predominant AA (393 cases and 132 controls) and EA (195 cases and 196 controls) ethnic groups from logistic regression models with or without adjustment for covariates
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
