| Title: | Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer |
| Journal: | JNCI Cancer Spectrum |
| Published: | 10 Aug 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35947687/ |
| DOI: | https://doi.org/10.1093/jncics/pkac061 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475354 |
| Citations: | 4 (2 in last 2 years) as of 8 Aug 2024 |
Publication 12278
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Abstract
BACKGROUND: The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes of castration-resistant prostate cancer and is associated with estrogen receptor positivity in postmenopausal breast cancer. Like breast cancer, endometrial cancer is another malignancy with hormone-dependent and hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate with hormone-independent cancer subtypes.</p>
METHODS: We employed a previously described classification of tumors in The Cancer Genome Atlas into genomic clusters. We determined HSD3B1 genotype frequencies by endometrial cancer genomic cluster and calculated the odds per adrenal-restrictive A allele for the largely hormone-independent copy-number (CN) high subtype vs other subtypes. An equivalent analysis was performed for the genomically similar, hormone-independent basal breast cancer subtype. Last, we performed survival analyses for UK Biobank participants with endometrial cancer by HSD3B1 genotype. All statistical tests were 2-sided.</p>
RESULTS: The adrenal-restrictive HSD3B1(1245A) allele was associated with the CN-high endometrial cancer subtype (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.14 to 2.32; P = .007). Similarly, HSD3B1(1245A) was associated with the basal breast cancer subtype (OR = 1.54, 95% CI = 1.13 to 2.08; P = .006). In the UK Biobank, endometrial cancer patients homozygous for HSD3B1(1245A) had worse overall (hazard ratio [HR] = 1.39, 95% CI = 1.16 to 1.68; P < .001) and cancer-specific (HR = 1.39, 95% CI = 1.14 to 1.70; P = .001) survival, consistent with the A allele being enriched in the more aggressive CN-high subtype.</p>
CONCLUSIONS: These findings suggest roles for adrenal-restrictive vs adrenal-permissive steroidogenesis, by way of rs1047303 genotype, in the development of and/or outcomes from at least 3 commonly hormone-associated types of cancer: prostate, breast, and endometrial.</p>
9 Keywords
- Androgen Antagonists
- Androgens
- Breast Neoplasms
- Endometrial Neoplasms
- Female
- Humans
- Multienzyme Complexes
- Progesterone Reductase
- Steroid Isomerases
5 Authors
- Jeffrey M McManus
- Roberto Vargas
- Peter S Bazeley
- Fredrick R Schumacher
- Nima Sharifi
1 Application
| Application ID | Title |
|---|---|
| 44578 | Phenotypic characterization of genetic variants associated with sex steroid differences |
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