Kittles R A, Panguluri R K, Chen W, Massac A, Ahaghotu C, Jackson A, Ukoli F, Adams-Campbell L, Isaacs W, Dunston G M
National Human Genome Center at Howard University, Washington, DC 20059, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Sep;10(9):943-7.
Androgens play an important role in the etiology of prostate cancer. The CYP17 gene encodes the cytochrome P450c17alpha enzyme, which is the rate-limiting enzyme in androgen biosynthesis. A T to C polymorphism in the 5' promoter region has recently been associated with prostate cancer. However, contradictory data exists concerning the risk allele. To investigate further the involvement of the CYP17 variant with prostate cancer, we typed the polymorphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotyped the CYP17 polymorphism in Nigerian (n = 56), European-American (n = 74), and African-American (n = 111) healthy male volunteers, along with African-American men affected with prostate cancer (n = 71), using pyrosequencing. Genotype and allele frequencies did not differ significantly across the different control populations. African-American men with the CC CYP17 genotype had an increased risk of prostate cancer (odds ratio, 2.8; 95% confidence interval, 1.0-7.4) compared with those with the TT genotype. A similar trend was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was significantly associated with higher grade and stage of prostate cancer (odds ratio, 7.1; 95% confidence interval, 1.4-36.1). The risk did not differ significantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prostate cancer risk and clinically advanced disease in African Americans.
雄激素在前列腺癌的病因学中起着重要作用。CYP17基因编码细胞色素P450c17α酶，它是雄激素生物合成中的限速酶。最近发现5'启动子区域的一个T到C多态性与前列腺癌有关。然而，关于风险等位基因存在相互矛盾的数据。为了进一步研究CYP17变体与前列腺癌的关系，我们在三个不同人群中对该多态性进行了分型，并评估了其与非裔美国人前列腺癌及临床表现的关联。我们使用焦磷酸测序技术对尼日利亚（n = 56）、欧美裔美国人（n = 74）和非裔美国人（n = 111）的健康男性志愿者以及患有前列腺癌的非裔美国男性（n = 71）的CYP17多态性进行了基因分型。不同对照组人群的基因型和等位基因频率没有显著差异。与TT基因型的非裔美国男性相比，CC CYP17基因型的非裔美国男性患前列腺癌的风险增加（优势比，2.8；95%置信区间，1.0 - 7.4）。在非裔美国前列腺癌患者的纯合变异基因型与临床表现之间也观察到了类似趋势。CC基因型与前列腺癌的更高分级和分期显著相关（优势比，7.1；95%置信区间，1.4 - 36.1）。风险在家族史或年龄方面没有显著差异。我们的结果表明，CYP17多态性的C等位基因与非裔美国人前列腺癌风险增加及临床晚期疾病显著相关。
