Endometriosis may double the risk for ovarian cancer

Endometriosis may double the risk for ovarian cancer

By I. Soussis MD

Women with endometriosis are 1.9 times more likely to develop ovarian cancer, but are at no higher risk for endometrial and cervical cancers, a meta-analysis suggests.

The study, “Impact of endometriosis on risk of ovarian, endometrial and cervical cancers: a meta-analysis,” was published in the journal Archives of Gynecology and Obstetrics.

While endometriosis is considered a benign gynecologic disease, it displays features similar to those seen in malignant tumors, including:

  • the ability to invade other tissues

  • a high rate of new blood vessel formation

  • development of local and distant sites of lesions

These characteristics of endometriosis rendered its classification as behaving similar to tumor-like lesions by the World Health Organization, and growing evidence suggests that the condition may represent an initial stage of tumor progression.

While some studies have associated endometriosis with an increased risk for developing different gynecologic tumors, namely ovarian and endometrial cancers, the results are conflicting.

Therefore, a team of researchers in China performed a meta-analysis to investigate the link between endometriosis and the risk for three gynecological cancers: ovarian, endometrial, and cervical.

Out of 8538 studies retrieved from several databases, they analyzed 25 studies, which included 15 cohort and 10 case-control studies. These studies had been conducted in different countries, including Taiwan, the U.S., Australia, Sweden, Denmark, the Netherlands, Japan, Canada, and Spain, with one study involving joint participation of multiple countries.

The researchers evaluated the risk factor between endometriosis and ovarian cancer in 23 studies, between endometriosis and endometrial cancer in 9 studies, and between endometriosis and cervical cancer in 3 studies.

They found that endometriosis was associated with an increased risk (1.9 times) for developing ovarian cancer. In fact, the ovary is one of the major target organs for the malignant transformation of endometriosis. An integrated analysis of different studies revealed a great overlap between the genetic alterations of both endometriosis and ovarian cancer.

Of note, researchers found that endometriosis increased the risk for developing some subtypes of ovarian cancer: endometrioid and clear-cell type.

No clear evidence supports a link between endometriosis and the risk for endometrial cancer, and endometriosis was not associated with an increased risk for cervical cancer.

Despite the authors’ efforts in making a robust comparison of the different studies using rigorous selection criteria, they were limited to the number of available articles about each cancer type. There were more ovarian cancer studies available, which could have influenced the observations to some extent, the study noted.

There is insufficient evidence to support the theory of endometriotic lesions as a precancerous lesion,” the researchers wrote.

Their meta-analysis suggests that endometriosis is a potential risk factor for developing ovarian cancer, but additional studies are required to understand further if endometriotic lesions are precancerous.

If endometriosis is considered a precancerous lesion, the current treatment management needs to be modified,” the researchers concluded, noting that patients with endometriosis need to be closely observed and rechecked regularly to prevent malignant changes.

My opinion

The association between endometriosis and clear-cell cancer of the ovary and endometrioid ovarian cancer is well established. This meta-analysis confirms it and also clarifies that there is no increased risk between endometriosis and endometrial and cervical cancer.

Women with endometriosis should have life-long regular follow up by their doctors.



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Endometriosis and endometrial cancer have common genetic causes

Endometriosis and endometrial cancer have common genetic causes

By I. Soussis MD

Both endometriosis and endometrial cancer have a genetic component. Genome-wide association studies (GWAS) identifying single nucleotide polymorphisms (SNPs) -differences in a single DNA building block, called a nucleotide-  associated with either disease.

Endometriosis and endometrial cancer may be linked, as suggested by the fact that higher levels of estrogen increase the risk for both diseases, which, in turn, is lessened with treatments such as contraceptive pills and hormonal therapies.

Moreover, both disorders correlate with greater risk for uterine fibroids and ovarian cancer. Further suggesting the link, cancer-related genetic changes, including dysregulation of genes, have been reported in endometriosis.

The new study, “Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses,” appeared in the journal Cancer Medicine.

Epidemiological studies have led to conflicting data regarding this potential association, which may have been due to small sample sizes, underdiagnosis and misdiagnosis of endometriosis, and inability to adjust for variables such as oral contraceptives, the scientists said.

As such, they conducted a GWAS, using separate datasets for endometriosis and endometrial cancer to study the extent of a common genetic cause for both diseases. 

The team subsequently combined the datasets in a meta‐analysis – a statistical study that combines the results of various studies — to find genetic loci, or specific spots in chromosomes, potentially associated with risk for both disorders.

In total, the datasets for endometriosis included 3,194 cases and 5,330 controls, while those for endometrial cancer had 2,057 cases and 3,866 controls. Results of the meta‐analysis were compared with those from a dataset including 4,402 endometrial cancer cases and 28,758 controls.

The results revealed the presence of weak to moderate, but significant, genetic overlap between the  diseases, as well as significant SNP pleiotropy, which refers to disease-associated SNPs correlating with variation in gene expression and/or DNA methylation -the addition of a methyl chemical group to DNA, regulating gene expression- in both disorders.

Thirteen distinct loci were associated with the diseases, with one locus -SNP rs2475335- located within the PTPRD gene, associated at a significant level. PTPRD is a commonly inactivated gene across different types of cancer. Deletions and mutations in this gene have been detected in numerous tumor types, including endometrial cancer. The PTPRD protein regulates the activation of STAT3, a transcription factor -proteins that control gene expression- previously implicated in both endometriosis and endometrial cancer.

The other identified risk loci contain candidate genes such as SKAP1, associated with ovarian cancer, potentially relevant as causes and/or treatment targets of endometriosis and endometrial cancer, the investigators said.

“Our genetic study indicates that endometriosis and endometrial cancer have a moderate, but significant, shared genetic etiology,” the researchers said. Studies are now needed to better understand how the identified risk loci affect both diseases, the team stated.

“Our genetic correlation analysis supports recent large epidemiological studies indicating an increased risk of endometrial cancer in women previously diagnosed with endometriosis,” according to the researchers.

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