HSD3B1 genetic research shows an association between the genotype and endometrial cancer

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The HSD3B1 gene could hold clues to predicting and treating endometrial cancer, according to a new discovery from the Lerner Research Institute at the Cleveland Clinic.

The researchers found that the HSD3B1 genotype was more common in women with type 2 Endometrial cancerAccording to the results published in JNCI . Cancer Spectrum. These patients show lower survival rates than those diagnosed with type 1 endometrial cancer, likely due to the fact that the patient’s type 2 cells are less hormonally dependent.

The findings are the latest step in untangling the role that the HSD3B1 genotype plays in hormone-driven cancers, as previous research has revealed its association with breast cancer and prostate cancer. This working group has been led in part by Cleveland Clinic researchers, clinicians, and scientists, and continues today with translational research and clinical trials.

HSD3B1 researchers are building a foundation for future options to treat and prevent cancer subtypes with a lower survival rate, says Niama Sharifi, MD, author of the research paper and director of the Lerner Institute for Genitourinary Malignancy Research Center.

Despite being one of the most common types of cancer among women, there is no test or screening test for endometrial cancer. Rates of this “underfunded and understudied” disease are rising in the United States, says Roberto Vargas, MD, co-author and associate staff member of the department of gynecological oncology at the Cleveland Clinic.

“For the past three decades, we have not moved the outcome standard,” says Dr. Vargas. “The discovery of the interaction between this gene and endometrial cancer could pave a way to more effectively screen and treat it.”

HSD3B1 is a gene that regulates androgens and estrogens by producing the enzyme that converts adrenal steroid precursors to androgens and estrogens. The HSD3B1 genotype is either adrenal permissive, which amplifies the process, or adrenal-restrictive, which limits it.

Dr. Sharifi likens the role of HSD3B1 in the adrenal pathway to how a dam controls water. The opening of the gates causes the water to rush in, but when the dam is closed, this flow is stopped.

Previous research has demonstrated how HSD3B1 genetics works and links it to hormone-related cancers, starting with castration-resistant prostate cancer. When a patient undergoes chemical or surgical castration to treat prostate cancer, the procedure stops one of the body’s pathways to produce androgens.

Dr. Sharifi says that when the body stops producing androgens or estrogens through the sex organs, the body can still produce these hormones through the adrenal pathway.

Castration aims to stop androgen production when tumors grow in response to the hormone. When the adrenal pathway begins to produce androgens, this can lead to a recurrence. Previous research links permissive adrenal HSD3B1 to worse outcomes in Castration-resistant prostate cancer across multiple individual groups.

Dr. Sharifi says HSD3B1 could act as a biomarker for breast and endometrial cancer subtypes because the ovaries stop producing estrogen after menopause. It can initiate the adrenal gland’s pathway to start producing those hormones. The average age of an endometrial cancer patient is 60 years, and the main symptom is irregular bleeding after menopause.

Recent research has investigated the possible association between the HSD3B1 genotype and types of postmenopausal breast cancer and endometrial cancer, in which cancer grows in response to estrogen.

Previous research linked to ER+ cancer in Postmenopausal women With the HSD3B1 genotype allowing adrenal gland. Sharifi’s research team, by analyzing the TCGA data, added to this finding by showing an association between the opposite HSD3B1 genotype, adrenal restriction, and a specific ER breast cancer subtype.

In endometrial carcinoma, the serous subtype has lower ER expression and is associated with a worse prognosis. According to the study, the adrenal-restricted HSD3B1 genotype was more associated with serous-type endometrial carcinoma. In addition, in an analysis of UK Biobank data, an adrenal-restrictive genotype was shown to be associated with worse outcomes among patients with endometrial cancer.

Jeff McManus, PhD, first author and research associate in the Department of Cancer Biology, says researchers will now need to validate the findings with much larger cohorts. This will involve examining the associations of HSD3B1 with survival rates within different cancer subtypes.

Ongoing collaborations with HSD3B1 include further research on the relationship of HSD3B1 to breast and endometrial cancer, as well as investigation of how HSD3B1 relates to response to radiotherapy. Clinical trials of Prostate cancer Held at the Cleveland Clinic, it will test how people with certain HSD3B1 genotypes respond to treatments.

The authors note that black women are more likely to inherit adrenal-restricting HSD3B1 and that some types of breast cancer and endometrial cancer have worse outcomes—both of which are more common in black women. Black women were twice as likely to die of uterine cancer than other racial groups in a study released in May from the National Cancer Institute.

“Reducing this difference in outcomes and trying to understand the genetic basis will be crucial to reducing (or eliminating) the differences that exist,” Vargas says.


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more information:
Jeffrey M McManus et al, Association between the heritability of adrenal-restrictive HSD3B1 and the hormone-independent subtypes of uterine and breast cancer, JNCI . Cancer Spectrum (2022). DOI: 10.1093/jncics/pkac061

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the quote: HSD3B1 gene search shows association between genotype and endometrial cancer (2022, September 12) Retrieved on September 12, 2022 from https://medicalxpress.com/news/2022-09-hsd3b1-gene-association-genotype-endometrial. html

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