Are fibroids genetic

Are Fibroids Genetic?

We're often asked if fibroids are genetic, and even more often, women with fibroids ask themselves "why me?" Generally speaking, uterine fibroids do not have a single identifiable cause, but are often attributed to family history, genetics, age, and/or race as contributing factors. To provide more clarity on what we know and what we don't know, we draw on commonly cited research to explain the genetic basis of fibroids.

Are Fibroids Hereditary?

Research has shown that genetics can contribute to the development of uterine fibroids, although genetics may not be the primary nor the singular cause. Rare genetic syndromes provide evidence supporting the idea that uterine fibroids have a genetic basis. For example, in Reed’s Syndrome, which is also called multiple cutaneous and uterine leiomyomatosis (MCUL), affected females show a higher prevalence of fibroids at an earlier age of onset with more severe symptoms [1]. In hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome, germline mutations in the Fumarate hydratase gene cause affected patients to develop benign tumors on the skin and in the uterus. Affected individuals are also at increased risk for kidney cancer [1, 6]. 

Studies of twins also point to genetics as a contributing factor in the development of uterine fibroids.

Monozygotic (identical) twins with uterine fibroids, who share all of their genes, are twice as likely to undergo hysterectomy when compared with dizygotic (fraternal) twins who share half of their genes. This observation is consistent with the expected rates for a genetically influenced trait [1].

The exact causes of uterine fibroid formation are not yet known but genetic differences and abnormalities are associated with increased risk of developing fibroids. Many epidemiological, molecular, and cytogenetic studies support this conclusion.

Do Fibroids Run in Your Family?

In addition to genetics, it's important to consider the role of other known risk factors.

Family History

Having a mother or grandmother with fibroids can certainly increase your risk for developing uterine fibroids. However, it does not guarantee you will have them. Statistically, if a woman's mother had fibroids, her risk of having them is about three times higher than average [2].

Genetics

Studies show that women with early onset uterine fibroids that develop before the age of 30 are more likely to have been genetically predisposed. Genetically influenced traits generally manifest at an earlier age of onset [1].

Diet

Poor diet can increase your risk for uterine fibroids--for example, frequent consumption of red meat and lack of fruits and vegetables [2]. Fatty foods that increase your likelihood for obesity also play a role in the potential development of fibroids. This is because fats can be used to make the steroid hormones, such as estrogen, which is linked to the growth of uterine fibroids [2,3].

Age

If you started your menstrual period at or before the age of 10, you are at increased risk for developing uterine fibroids. One explanation for this is the increased number of cell divisions that can occur and the higher probability of mutation or uncontrolled proliferation during a longer reproductive age window [3].

Uterine fibroids are most likely to develop when women are in their 30s to 40s. Some women may develop fibroids as early as their 20s. After menopause, uterine fibroids typically shrink. Benign uterine tumors are extremely common in women of reproductive age.

Race

Fibroids are more prevalent in Black women than White women, even after adjustment for other known risk factors. In fact, the prevalence of uterine fibroids is 3 to 9 times higher in Black women than in White women [2,5].

Fibroids Genetic Predisposition

There are several genes that are associated with uterine leiomyoma development. In one multi-ethnic study, 14 loci, or physical locations of genes/other DNA sequences on a chromosome, were identified as controlling or containing plausible uterine fibroid predisposition genes. These genes include: TERT, TERC, OBFC1 (which are all involved in regulating telomere length, as uterine fibroid cells have shortened telomeres), ATM and TP53 (which guard stability of the genome through their involvement in DNA damage response), as well as ESR1, GREB1, WT1, MED12, WNT4, FOXO1, DMRT1, SALL1, and CD44 (which play a role in genitourinary development) [6]. Mutations in these genes or their regulation could contribute to the development of uterine fibroids.

A genome-wide association study showed that genes previously associated with endometriosis and involved in hormone-signaling pathways are also associated with uterine leiomyoma. When examining the co-occurence of endometriosis and uterine fibroid across three independent study groups, it was found that women with a history of endometriosis are at elevated risk for reporting uterine fibroids [6, 7].

Genetics and the Development of Fibroids

 

Benign tumors within the same uterus can have different genetic mutations. On the other hand, uterine fibroids from two unrelated patients may have nearly identical defects.

Constitutional Variants

Constitutional DNA refers to the genetic material from reproductive cells that is incorporated into the DNA of every cell in the body of the offspring. Genome-wide association studies have analyzed common variants in the constitutional human genome. In Japanese women, benign uterine tumors (leiomyomas) were associated with structural variants on chromosomes 10, 11, and 22. Another study of White women identified fatty acid synthase gene (FASN) on chromosome 17 as a candidate gene involved in predisposition to uterine fibroids [8].

Somatic Changes

A somatic alteration is a change to the DNA that occurs after conception, during or after cell division. Somatic mutations can occur in all cells of the body except sperm and egg cells. Because they don’t affect the sex cells, somatic mutations cannot be passed on to offspring. Cytogenetic studies have shown that approximately 40% of uterine leiomyomas have recurrent structural chromosome changes from somatic alterations such as rearrangements of chromosomes 12 and 6 and deletions on chromosome 7 [8].

The MED12 gene is located on the X chromosome and MED12 mutations are found in approximately 70% of benign uterine tumors [8].

Epigenetics

Changes that are independent from the DNA sequence, such as acetylation or methylation, can regulate the expression of genes. Genes can be activated or silenced as a result of epigenetic changes. Studies have shown that uterine fibroids are associated with the increased silencing of tumor suppressor genes, activation of oncogenes, or overexpression of genes that regulate estrogen [8,9]. 

FAQ

Do fibroids run in families?

Yes, uterine fibroids can run in families, especially if your mom or grandmother had them. However, a family history of uterine fibroids does not guarantee you will get them too.

What are the risk factors for developing uterine fibroids?

Some risk factors include a diet low in vegetables and fruits but high in red meats and fats, being of reproductive age, family history of fibroids, African American race, and genetic variants.

Are fibroids hereditary?

Yes, some fibroids develop as a result of inherited genetic mutations. However, not all uterine fibroids develop from hereditary reasons. Other lifestyle and environmental factors play a role too.

How do fibroids develop as a result of genetic factors?

You can inherit DNA mutations, acquire gene mutations as your body’s cells divide and replicate, and/or acquire gene mutations as a result of environmental factors and lifestyle choices.

References

[1] Jennelle C. Hodge, Cynthia C. Morton, Genetic heterogeneity among uterine leiomyomata: insights into malignant progression, Human Molecular Genetics, Volume 16, Issue R1, 15 April 2007, Pages R7–R13, https://doi.org/10.1093/hmg/ddm043

[2] https://www.womenshealth.gov/a-z-topics/uterine-fibroids

[3] Laganà AS, Vergara D, Favilli A, La Rosa VL, Tinelli A, Gerli S, Noventa M, Vitagliano A, Triolo O, Rapisarda AMC, Vitale SG. Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease. Arch Gynecol Obstet. 2017 Nov;296(5):855-867. doi: 10.1007/s00404-017-4515-5. Epub 2017 Sep 5. PMID: 28875276.

[4] Stewart, EA. Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas. UpToDate. Accessed February 2021. 

[5] Stewart, EA., Laughlin-Tommaso, SK. Patient education: Uterine fibroids (Beyond the Basics). UpToDate. Accessed February 2021. 

[6] Välimäki N, Kuisma H, Pasanen A, Heikinheimo O, Sjöberg J, Bützow R, Sarvilinna N, Heinonen HR, Tolvanen J, Bramante S, Tanskanen T, Auvinen J, Uimari O, Alkodsi A, Lehtonen R, Kaasinen E, Palin K, Aaltonen LA. Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. Elife. 2018 Sep 18;7:e37110. doi: 10.7554/eLife.37110. PMID: 30226466; PMCID: PMC6203434.

[7] Gallagher, C.S., Mäkinen, N., Harris, H.R. et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun 10, 4857 (2019). https://www.nature.com/articles/s41467-019-12536-4

[8] Ordulu Z. Fibroids: Genotype and Phenotype. Clin Obstet Gynecol. 2016 Mar;59(1):25-9. doi: 10.1097/GRF.0000000000000177. PMID: 26710305; PMCID: PMC4733577.

[9] Dvorská D, Braný D, Danková Z, Halašová E, Višňovský J. Molecular and clinical attributes of uterine leiomyomas. Tumour Biol. 2017 Jun;39(6):1010428317710226. doi: 10.1177/1010428317710226. PMID: 28653894.

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The Fibroid Specialists of University Vascular are leading providers of uterine fibroid embolization (UFE), the least invasive treatment option for women suffering from uterine fibroids. Our physicians have devoted their expertise to helping women overcome fibroids without hysterectomy or major surgery. 

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