Department of Medical Oncology, National Cancer Centre, Singapore.
Urol Oncol. 2013 Nov;31(8):1553-60. doi: 10.1016/j.urolonc.2012.02.009. Epub 2012 May 5.
Recently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.
We performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.
In the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥ 7 (OR = 1.76, 95% CI = 1.14-2.73) and prostate-specific antigen (PSA) levels of ≥ 10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01-2.63), as well as for rs6983267 GG with stage 3-4 CaPs (OR = 1.91, 95% CI = 1.01-3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10-4.32).
This exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.
最近，几项全基因组关联研究表明，染色体 8q24 和 17q 上的 5 个多态性变异与白种人前列腺癌（CaP）风险相关，特别是那些具有侵袭性临床病理特征的患者。本研究旨在评估这些变异在新加坡亚裔男性中对 CaP 易感性的影响。
我们在 289 名中国 CaP 患者和 412 名健康对照者（144 名中国人、134 名马来人和 134 名印度人）中进行了病例对照研究，并检测了这 5 个单核苷酸多态性（SNP）与 CaP 的关联。
在健康对照组中，rs16901979 A 等位基因频率在中国人中最高（0.32），而在马来人（0.13；P < 0.0001）或印度人（0.09；P < 0.0001）中最低；rs6983267 G 等位基因频率在印度人中最高（0.51），而在中国人中（0.42；P = 0.041）或马来人中（0.43；P = 0.077）最低；而 rs1859962 G 等位基因频率在印度人中最高（0.56），而在中国人中（0.40；P = 0.0002）或马来人中（0.38；P < 0.0001）最低。在中国人中，rs4430796 TT 基因型个体患 CaP 的风险增加，采用隐性模型（比值比（OR）= 1.56，95%置信区间（CI）= 1.04-2.33）。rs4430796 TT 与 Gleason 评分≥7（OR = 1.76，95% CI = 1.14-2.73）和诊断时前列腺特异性抗原（PSA）水平≥10ng/ml（OR = 1.63，95% CI = 1.01-2.63）显著相关，rs6983267 GG 与 3-4 期 CaP 显著相关（OR = 1.91，95% CI = 1.01-3.61）。还发现了这些基因相互作用对疾病风险的累积影响，具有至少 2 个易感基因型的个体风险约增加 1 倍（OR = 2.18，95% CI = 1.10-4.32）。
这项探索性分析表明，先前描述的 5 个遗传变异可能与新加坡男性的前列腺癌风险有关。
