Uterine Fibroids

Uterine fibroids — also called uterine leiomyomata — are benign (non-cancerous) growths of the muscular wall of the uterus. They are the most common tumor of the female reproductive tract and the leading cause of hysterectomy, and two genome-wide association studies have mapped part of the genetics behind them.

Three loci, then twenty-nine

The first genome-wide study, Cha et al. 2011, tested 1,607 people with clinically diagnosed fibroids against 1,428 without, replicated in a further 3,466 cases and 3,245 controls, and found three genome-wide-significant loci. One of them, near TNRC6B on chromosome 22, is rs12484776 on this page, with an odds ratio around 1.23.

A much larger 2019 study, combining 35,474 people with fibroids and 267,505 without, found 8 new loci and confirmed 21 already known, bringing the total to 29. This page holds 14 of that study's loci.

A real link to a very differently-diagnosed condition

The 2019 study's most notable finding was not another locus — it was that 4 of the fibroid loci are also associated with endometriosis risk, a condition where tissue similar to the uterine lining grows outside the uterus. The two conditions are diagnosed differently and can look clinically distinct, but a separate analysis of 402,868 women found that a history of endometriosis was associated with at least double the risk of a later uterine fibroid diagnosis. Shared genetic loci plus a real epidemiological association, in the same study, is a stronger case for common biological ground than either finding would be alone.

The same study also looked specifically at heavy menstrual bleeding — one of the most disruptive symptoms fibroids can cause — by comparing 3,409 people with that symptom against 199,171 without it. Three of the 29 fibroid loci, near TERT, FGFR4 and ATM, were specifically associated with heavy bleeding rather than with having fibroids at all. That is a distinction worth having: not every fibroid-associated gene affects the disease the same way, and at least three affect a specific, clinically important symptom rather than fibroid risk in general.

A third study belongs here too. Rafnar et al. 2018 meta-analysed two GWAS in 16,595 cases and 523,330 controls, all European women, finding 21 variants at 16 loci. Five were already known cancer-risk variants — in TP53, TERT, ATM (twice), and OBFC1 — and four more sat at established hormone-related-trait loci shared with endometriosis and breast cancer risk. A polygenic score built from the findings correlated with broader cancer risk in an independent population, reinforcing the same fibroid-cancer genetic overlap the 2019 study above found through endometriosis specifically. This page's rs141379009, in ATM, matches this paper's own tumor-risk-gene theme directly. Seven more of this page's variants — three in GABRG1 and one each in CWH43, SPATA18, SCFD2, and TNFSF12-TNFSF13 — come from this same 16-locus set, though the paper's own abstract does not detail each individually.