Genes that increase the risk of uterine fibroids

Uterine fibroids are a problem for a lot of women, especially after age 30. Fibroids are benign tumors that grow in the muscle cells of the uterus. While estimates vary, at least half of American women who are of reproductive age have fibroids.[ref ]

This article digs into the causes of fibroids, explains how your genetic variants can add to the susceptibility, and offers solutions backed by research.

Uterine fibroids:

Symptoms of fibroids include:

  • painful or heavy periods
  • anemia
  • frequent need to urinate
  • painful sex
  • low back pain

Fibroids can also play a role in infertility for some women. But not all women have symptoms with fibroids – it depends on the location and size.

Uterine leiomyoma, another name for fibroids, means smooth muscle tumor.

Causes of fibroids

You would think that something that affects more than half of women would be well understood and have good solutions available. Oddly enough, there are still questions surrounding the causes of fibroids, and a lot of the solutions available are either ineffective or come with significant side effects.

Genetics plays a role in the susceptibility to fibroids, but, as you will see, lifestyle factors are also important.[ref ]

Stem cells and growth

Fibroids are medically classified as benign tumors, meaning they are nearly always non-cancerous growths.

Genetics studies show that a fibroid will arise from one cell that has somewhat unchecked growth. Stem cells are present in the muscles of the uterus, which need to be able to grow and change both monthly and during pregnancy.[ref ][ref ]

The stem cells in the uterine muscles are capable of replicating into more muscle tissue – that is their whole purpose. When there is DNA damage in a growth-related gene, the stem cells go on a growth spree and become a fibroid. Additionally, the conditions for growth and proliferation of the cells need to be right (see below). The body’s normal way of dealing with damaged DNA also needs to be overridden.[ref ]

Estrogen, progesterone, and growth

Estrogen and progesterone are involved in the formation and growth of fibroids, which occur mainly during the reproductive years when estrogen and progesterone levels are high. Fibroids usually decrease in size once a woman reaches menopause.

The cells in a fibroid have increased estrogen and progesterone receptors. Animal studies show that the addition of estrogen alone, or estrogen plus progesterone, can increase the size of fibroids.[ref ]

In the uterus, estrogen upregulates IFG-1 (insulin-like growth factor 1), EGFR, TGF-beta1. These are all growth-related molecules.[ref ]

Interleukin-1 is an inflammatory cytokine that can inhibit REST, which is a tumor suppressor. Interleukin-1 happens to also be upregulated in fibroid tissue.[ref ]

Environmental exposure

Adding fuel to the fibroid fire, exposure to endocrine-disrupting chemicals such as BPA and phthalates also increases the risk and growth of fibroids.

BPA is a component of plastics and a known endocrine disruptor, similar in structure to estrogen. A cell study shows that exposure to low levels of BPA increases the proliferation of fibroid cells. [ref ] A study of 495 women who were diagnosed with fibroids found that they had higher concentrations of BPA in them than women without fibroids.[ref ]

2-hydroxy-4-methoxybenzophenone, a UV filter found in sunscreens, has links to an increase in fibroids.[ref ]

Phthalates, found in plastics, vinyl, and fragrances, act as endocrine-disrupting chemicals and have links to an increased risk of fibroids. This was especially true in women who carried the GSTM1 null genotype.[ref ]

In-utero and infant exposures:

Early-onset fibroids are linked to exposure to diethylstilbestrol (DES) in-utero. DES, an estrogen medication, was used from 1940 to 1971 for pregnant women. The daughters of women who took DES were at a higher risk for fibroids and at a younger age.[ref ]

Infectious agents:

Infection with cytomegalovirus in the uterine tissue leads to an associated 6-fold increase in the risk of fibroids. On the other hand, Chlamydia trachomatis decreased the risk of fibroids.[ref ][ref ]


Genetic variants that increase the risk of fibroids:


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None of these genetic variants cause fibroids on their own. Instead, they all add to the susceptibility. You will notice these variants are involved in the vascular system (important for blood vessels for the fibroid), DNA repair pathways (important in proliferation), and estrogen pathways.

ACE gene: codes for the angiotensin-converting enzyme, which is important in vascular diseases.

Check your genetic data for rs4343  (23andMe v4, v5; AncestryDNA):

  • A/A: typical (ACE insertion/insertion)
  • A/G: increased risk of fibroids (ACE deletion/insertion)
  • G/G: increased risk of fibroids (ACE deletion/deletion)

Members: Your genotype for rs4343 is .

XPC gene: codes for part of the DNA repair pathway

Check your genetic data for rs2228000 (23andme v4, v5; AncestryDNA):

  • G/G: typical risk of fibroids
  • A/G: decreased risk of fibroids
  • A/A: decreased risk of fibroids[ref ]

Members: Your genotype for rs2228000 is .

XPG gene: codes for part of the DNA repair pathway

Check your genetic data for rs873601 (23andMe v5; AncestryDNA):

  • A/A: increased risk of fibroids[ref ]
  • A/G: typical risk of fibroids
  • G/G: typical risk of fibroids

Members: Your genotype for rs873601 is .

CYP1B1 gene: estrogen metabolism

Check your genetic data for rs1056827 A119S (23andMe v4 only):

  • C/C: typical
  • A/C: somewhat increased risk of uterine fibroids
  • A/A: increased risk of breast cancer[ref ] increased risk of uterine fibroids[ref ]

Members: Your genotype for rs1056827 is .

ESR1 gene: estrogen alpha receptor 1

Check your genetic data for rs2234693 Pvull (23andMe v4, v5; AncestryDNA):

  • T/T: slightly lower risk of fibroids[ref ]
  • C/T: typical risk of fibroids
  • C/C: typical risk of fibroids

Members: Your genotype for rs2234693 is .

CCND1 gene: cell cycle regulatory protein

Check your genetic data for rs9344 (AncestryDNA only):

  • G/G: typical risk of fibroids
  • A/G: slightly increased risk of fibroids
  • A/A: increased risk of fibroids[ref ]

Members: Your genotype for rs9344 is .

FASN gene: fatty acid synthase

Check your genetic data for rs4247357 (23andMe v4; AncestryDNA):

  • T/T: increased risk of fibroids[ref ]
  • G/T: increased risk of fibroids
  • G/G: typical risk of fibroids

Members: Your genotype for rs4247357 is .

GSTM1 gene: glutathione-S transferase, part of phase II detoxification

Check your genetic data for rs366631 (23andMe v4 only):

  • A/A: deletion (null) GSTM1 gene. Five-fold increased risk of fibroids with higher phthalate exposure[ref ] (This is actually the most common genotype in most populations.)
  • A/G: GSTM1 present
  • G/G: GSTM1 present

Members: Your genotype for rs366631 is .

 


Lifehacks for fibroids:

Dietary associations:

Women eating more than 2 servings of fruits per day had a slightly decreased risk of uterine fibroids compared to women eating less than 2 servings per week.  A higher intake of animal sources of vitamin A seems linked to a slightly decreased risk of uterine fibroids.[ref ]

Another study found that frequent milk and soybean use was linked with an increased risk of fibroids.[ref ] Unfortunately, the study lumped both of those together as a category, so I’m not sure which one was important. The implication here is that additional phytoestrogens or bovine hormones could increase fibroids.

Food additives, sweeteners, and preserved foods have links to an increased risk of fibroids. (Not really helpful since the study doesn’t really narrow down or define those terms.)[ref ]

Oral contraceptive use has links to an increased risk of fibroids.[ref ] Alternatively, some types of oral contraceptives can also be used to slow menstrual bleeding and decrease the symptoms of fibroids.

Flavonoids:

The fact that increased fruit intake and decreased preserved foods are linked to fewer fibroids leads one to think that natural polyphenols in fruits and vegetables may be good for fibroids.

EGCG:  A randomized controlled trial of green tea extract (800 mg, 45% EGCG) found that the women consuming the green tea extract had a reduction in fibroid size and a decrease in blood loss. The women in the placebo arm of the trial had an increase in fibroid size.[ref ] You can get green tea extract at your local health food store. Be sure to read the label to determine the amount and percentage EGCG.

Kaempferol is a flavonoid that in cell culture studies seems to inhibit the proliferation of fibroid cells.  It also decreased IGF1 and VEGF, both of which are thought to be involved in the growth of fibroids.[ref ]

Resveratrol in a cell study reduced the growth of fibroids.[ref ]

Curcumin has also been shown in tissue studies to stop the growth of fibroid tissue.[ref ]

Avoid phthalates and BPA:

Phthalates are a chemical found in plastics, vinyl, and artificial fragrances (personal care products, air fresheners, and laundry products). They act as estrogen mimics in the body. The level of phthalate metabolites is associated with the size of fibroids – more phthalates in the body = bigger fibroids.[ref ][ref ]

Similarly, higher BPA levels have links to increased odds of fibroids. BPA can be found in some plastics, household dust, and thermal printed receipts.

What can you realistically do to avoid phthalates and BPA? Check your personal care products for phthalates, and look for laundry products without artificial fragrances included. Dusting and vacuuming regularly have been shown to decrease BPA. Handling thermal printed receipts, especially with wet hands, increases BPA fairly significantly in the body.

NSAIDs and aspirin:

While not without potential long-term side effects drawbacks, using anti-inflammatory drugs, such as ibuprofen, can be effective for reducing heavy menstrual flow.[ref ] Aspirin in cell studies reduced fibroid proliferation.[ref ]

 


Related Genes and Topics:

Thyroid Genes: Autoimmunity and Hypothyroidism
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Detoxifying Phthalates: Genes and Diet
Plastics are everywhere – and a source of the chemicals that we are exposed to on a daily basis. One component of plastics is a class of compounds referred to as phthalates, which can act as an endocrine disruptor and mimic estrogen.