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降低遗传性乳腺癌卵巢癌综合征突变携带者患妇科癌症的风险:道德困境与双重效应原则

Reducing the Risk of Gynecologic Cancer in Hereditary Breast Ovarian Cancer Syndrome Mutation Carriers: Moral Dilemmas and the Principle of Double Effect.

作者信息

Casey Murray Joseph, Salzman Todd A

机构信息

Creighton University, Omaha, NE, USA.

出版信息

Linacre Q. 2018 Aug;85(3):225-240. doi: 10.1177/0024363918788340. Epub 2018 Jul 20.

DOI:10.1177/0024363918788340
PMID:30275608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6161234/
Abstract

Hereditary breast ovarian cancer (HBOC) syndrome is an autosomal dominant disease linked to mutations in the and genes in 90 percent of affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives (COCs). Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification of prophylactic surgery and the use of COC to reduce the risk of gynecologic cancer in HBOC syndrome mutation carriers. Hereditary breast ovarian cancer syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in most affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives. Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification for those unfavorable effects.

摘要

遗传性乳腺癌卵巢癌(HBOC)综合征是一种常染色体显性疾病,在90%的受影响家族中与BRCA1和BRCA2基因的突变有关。女性突变携带者极易患侵袭性、通常会扩散、往往致命的盆腔腹部癌。在40岁之前通过手术切除内生殖器以及使用作为复方口服避孕药(COC)已销售多年的雌激素 - 孕激素制剂,可显著降低这种癌症风险。这两种降低风险的方法都有不良影响。基于双重效应原则,本文论证了预防性手术以及使用复方口服避孕药以降低HBOC综合征突变携带者患妇科癌症风险的伦理合理性。遗传性乳腺癌卵巢癌综合征是一种常染色体显性疾病,在大多数受影响家族中与BRCA1和BRCA2基因的突变有关。女性突变携带者极易患侵袭性、通常会扩散、往往致命的盆腔腹部癌。在40岁之前通过手术切除内生殖器以及使用作为复方口服避孕药已销售多年的雌激素 - 孕激素制剂,可显著降低这种癌症风险。这两种降低风险的方法都有不良影响。基于双重效应原则,本文论证了这些不良影响的伦理合理性。

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10

本文引用的文献

1
Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers.卵巢切除术后激素替代疗法与 BRCA1 突变携带者的乳腺癌风险。
JAMA Oncol. 2018 Aug 1;4(8):1059-1065. doi: 10.1001/jamaoncol.2018.0211.
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Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.应用卵巢癌风险算法和频繁 CA125 检测对家族性卵巢癌风险升高的女性进行卵巢癌早期检测:两项筛查试验的联合结果。
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The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation.生殖生活对有家族病史或携带BRCA突变的女性患乳腺癌风险的影响。
Oncotarget. 2017 Feb 7;8(6):9144-9154. doi: 10.18632/oncotarget.13423.
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Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas.子宫外 Müller 氏癌分子改变的形态学关联
Mod Pathol. 2016 Aug;29(8):893-903. doi: 10.1038/modpathol.2016.82. Epub 2016 May 6.
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Müllerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery.遗传性乳腺癌卵巢癌综合征中的苗勒管腹腔内癌转移:对降低风险手术的影响
Fam Cancer. 2016 Jul;15(3):371-84. doi: 10.1007/s10689-016-9878-4.
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Mean Age of Mothers is on the Rise: United States, 2000-2014.母亲平均年龄呈上升趋势:美国,2000 - 2014年。
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Epidemiology of Patients with Ovarian Cancer with and Without a BRCA1/2 Mutation.携带和不携带BRCA1/2基因突变的卵巢癌患者的流行病学。
Mol Diagn Ther. 2015 Dec;19(6):351-64. doi: 10.1007/s40291-015-0168-x.
9
Should risk-reducing surgery in women from hereditary breast ovarian cancer families be confined to removal of the fallopian tubes with ovarian conservation?
Womens Health (Lond). 2015 Jul;11(4):423-7. doi: 10.2217/whe.15.26. Epub 2015 Aug 6.
10
Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.TP53的分子改变是卵巢高级别浆液性癌的一个决定性特征:对癌症基因组图谱卵巢研究中缺乏TP53突变病例的重新审视。
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