Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer.
Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer.
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DOI：
10.1016/j.ijrobp.2010.07.036
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Rosenstein BS
中科院分区：
文献类型：
--
作者：
Kerns SL;Ostrer H;Stock R;Li W;Moore J;Pearlman A;Campbell C;Shao Y;Stone N;Kusnetz L;Rosenstein BS
在接受外照射放射治疗（EBRT）的非洲裔美国人前列腺癌患者中，确定与勃起功能障碍（艾德）相关的单核苷酸多态性（SNP）。采用男性性健康量表（SHIM）五项问卷，对接受EBRT治疗的非裔美国前列腺癌患者队列进行艾德发展随访。最终分析包括27例病例（治疗后SHIM评分≤ 7）和52例对照（治疗后SHIM评分≥ 16）。使用Affymetrix 6.0阵列上基因分型的1909，000个SNP进行了全基因组关联研究。我们确定了位于促卵泡激素受体（FSHR）基因的SNP rs 2268363，在校正多重比较后与艾德显著相关（未校正p值= 5.46×10−8; Bonferroni p值= 0.028）。我们确定了另外四个SNP，它们倾向于与未调整的p值< 10 - 06显著相关。人群亚结构的推断显示，与对照组相比，病例的非洲血统比例更高（77%比60%，p=0.005）。与仅包括临床变量的模型相比，将估计的祖先和四个排名靠前的SNP合并的多变量逻辑回归模型是更准确的艾德分类器。据我们所知，这是第一个全基因组关联研究，以确定与放疗引起的不良反应相关的SNP。值得注意的是，被证明与艾德显著相关的SNP位于其编码产物在雄性性腺发育和功能中起作用的基因内。该项目的另一个关键发现是，与艾德最密切相关的四个SNP特异于非洲血统的人，因此如果筛查欧洲血统的队列，则不会被识别。本研究证明了全基因组方法研究辐射损伤遗传易感性的可行性。
To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African American prostate cancer patients treated with external beam radiation therapy (EBRT). A cohort of African American prostate cancer patients treated with EBRT was followed for development of ED using the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score ≤ 7) and 52 controls (post-treatment SHIM score ≥ 16). A genome-wide association study was performed using ∼909,000 SNPs genotyped on Affymetrix 6.0 arrays. We identified SNP rs2268363, located in the follicle stimulating hormone receptor (FSHR) gene, as significantly associated with ED after correcting for multiple comparisons (unadjusted p-value = 5.46×10−8; Bonferroni p-value = 0.028). We identified four additional SNPs that tended toward significant association with unadjusted p-value < 10−06. Inference of population substructure revealed that cases had a higher proportion of African ancestry compared to controls (77% compared to 60%, p=0.005). A multivariate logistic regression model that incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate classifier of ED than a model that included only clinical variables. To the best of our knowledge, this is the first genome wide association study to identify SNPs associated with adverse effects resulting from radiotherapy. It is important to note that the SNP that proved significantly associated with ED is located within a gene whose encoded product plays a role in male gonad development and function. Another key finding of this project is that the four SNPs most strongly associated with ED were specific to people of African ancestry and would therefore not have been identified had a cohort of European ancestry been screened. This study demonstrates the feasibility of a genome-wide approach to investigate genetic predisposition to radiation injury.
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影响因子：
45.3
作者：
Talcott, JA;Manola, J;D'Amico, AV
通讯作者：
D'Amico, AV
DOI：
10.1016/s0360-3016(01)02690-6
发表时间：
2002-01-01
影响因子：
7
作者：
Safwat, A;Bentzen, SM;Hendry, JH
通讯作者：
Hendry, JH
DOI：
10.1016/j.ijrobp.2007.04.012
发表时间：
2007-11-01
影响因子：
7
作者：
Ho, Alice Y.;Fan, Grace;Rosenstein, Barry S.
通讯作者：
Rosenstein, Barry S.
影响因子：
7
作者：
Robbins, Christiane;Torres, Jada Benn;Carpten, John
通讯作者：
Carpten, John
影响因子：
9.8
作者：
Montana, G;Pritchard, JK
通讯作者：
Pritchard, JK