Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer.
Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer.
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DOI：
10.1093/jncics/pkac061
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发表时间：
2022-09-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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生殖系变异rs 1047303（HSD 3B 1 [1245 A/C]）限制或促进肾上腺前体产生强效雄激素和雌激素，影响去势抵抗性前列腺癌的结局，并与绝经后乳腺癌的雌激素受体阳性相关。与乳腺癌一样，子宫内膜癌是另一种恶性肿瘤，具有子宫内膜依赖性和子宫内膜非依赖性亚型。我们假设肾上腺限制性HSD 3B 1基因型与非肿瘤依赖性癌症亚型相关。我们采用了先前描述的癌症基因组图谱中的肿瘤分类为基因组簇。我们通过子宫内膜癌基因组簇确定了HSD 3B 1基因型频率，并计算了每个肾上腺限制性A等位基因在很大程度上不依赖于基因组拷贝数（CN）的高亚型与其他亚型的比值。对基因组相似的非乳腺癌依赖性基底乳腺癌亚型进行了等效分析。最后，我们对患有子宫内膜癌的英国生物样本库参与者进行了生存分析。所有统计检验均为双侧检验。肾上腺限制性HSD 3B 1（1245 A）等位基因与CN高子宫内膜癌亚型相关（比值比[OR] = 1.63，95%置信区间[CI] = 1.14至2.32; P = 0.007）。同样，HSD 3B 1（1245 A）与基底层乳腺癌亚型相关（OR = 1.54，95%CI = 1.13 - 2.08; P = 0.006）。在英国生物样本库中，HSD 3B 1（1245 A）纯合子的子宫内膜癌患者总体上更差，（风险比[HR] = 1.39，95% CI = 1.16至1.68; P < .001）和癌症特异性（HR = 1.39，95% CI = 1.14至1.70; P = .001）生存率，与A等位基因在更具侵袭性的CN-高亚型中富集一致。这些发现表明，通过rs 1047303基因型，肾上腺限制性与肾上腺允许性类固醇生成在至少3种常见乳腺癌相关类型的癌症（前列腺癌、乳腺癌和子宫内膜癌）的发展和/或结局中的作用。
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. 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. 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. 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.
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影响因子：
11.5
作者：
Ricciardelli, Carmela;Bianco-Miotto, Tina;Tilley, Wayne D.
通讯作者：
Tilley, Wayne D.
影响因子：
64.5
作者：
Chang KH;Li R;Kuri B;Lotan Y;Roehrborn CG;Liu J;Vessella R;Nelson PS;Kapur P;Guo X;Mirzaei H;Auchus RJ;Sharifi N
通讯作者：
Sharifi N
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
通讯作者：
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