在全球范围内，前列腺癌已经成为男性仅次于肺癌的第二常见恶性肿瘤。除了公认的年龄、种族以及家族
遗传史外，前列腺癌的相关危险因素目前尚不明确。尽管大量临床研究探究了饮食、生活习惯、各类药物以及环
境对前列腺癌的影响，研究结果仍存在争议。本文总结了当前有关前列腺癌相关危险因素的最新临床证据，以期
为未来前列腺癌的防治工作提供参考。
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[1]刘阳阳,王梁,刘志宇.前列腺癌相关危险因素的研究进展[J].泌尿外科杂志(电子版),2022,14(03):8-14.DOI:10.20020/j.CNKI.1674-7410.2022.03.03
前列腺癌是成年男性常见的泌尿系统恶性肿瘤 之一[1]，根据相关数据显示，2020年全球新发前列腺 癌病例 141.43万人，全球新发死亡病例 37.53万人， 前列腺癌已成为仅次于肺癌的第二大男性常见恶性 肿瘤，也是导致全球男性死亡的第五大原因[2]。随着 治疗模式的改变以及早期前列腺癌筛查对象标准的 调整，欧美等西方国家的前列腺癌发病率及死亡率 呈相对稳定趋势。而在亚洲地区，尤其是中国，前 列腺癌的发病率及死亡率逐年升高 [3]。年龄、种族及 家族史是目前比较明确的前列腺癌危险因素[4]，吸 烟、饮酒、饮食结构等因素与前列腺癌的关系尚不 明确。本综述旨在总结当前前列腺癌的相关危险因 素，为前列腺癌的防治工作提供参考。
1 种族与遗传因素
1.1 种族 在目前公认的前列腺癌危险因素中，种 族是其中之一。许多研究均表明黑人男性更容易被 诊断为患前列腺癌，较之非西班牙裔白人，黑人罹 患前列腺癌的风险高出 2.5倍，且更容易发生远处转 移[5]。Robert 等[6] 通过对 306 100 名成年男性随访研 究发现，黑人种族与前列腺癌特异性死亡率呈正相 关 （HR： 1.09， 95% CI： 1.04~1.15， P<0.01）。 2020年 JAMA 发表了关于种族与前列腺癌发生率的 相关文献[7]，通过对 2 280名非洲裔美国男性长达 7.6 年 （中位随访时间） 的随访研究发现，前列腺癌进 展发生率分别为 59.9%与 48.3%，差异有统计学意 义 （P<0.01）。而不同种族间前列腺癌远处转移 率 （P=0.49） 及前列腺癌特异性死亡率之间并无统 计学差异 （P=0.82）。
1.2 家族史 此外，家族史与前列腺癌具有明确的 相关性。Barber等[8]对 37 002名美国男性进行的一项 随访时间长达 16年的前瞻性研究结果显示，具有前 列腺癌家族史的成年男性，其本人前列腺癌发病率 增加 68% （95%CI：1.53~1.83）。另一项研究也表 明，当一名成年男性的兄弟或父亲被诊断患有前列 腺癌时，该男子本人罹患前列腺癌的风险比正常成 年男性高出 2~4倍[9]。Michał等[10] 研究结果显示，当 一级家属患前列腺癌时，本人患前列腺癌的风险增 加了 1.48 倍 （RR：2.48，95%CI：2.25~2.74），而 当有两个或两个以上一级家属患前列腺癌时，本人 患前列腺癌的风险升高 3.39倍 （RR：4.39，95%CI： 2.61~7.39）。因此对于有前列腺癌家族史，尤其是 一级亲属罹患前列腺癌的成年男性，更应该注重前 列腺癌筛查及定期随访。
1.3 分子水平 目前已发现多个基因突变与前列腺 癌相关。研究发现具有 BRCA1、BRCA2、MMR、 HOXB13、CHEK2 和 NBS1 等胚系突变的成年男 性，其前列腺癌发病风险明显升高[11]。在 2021 年颁 布的前列腺癌筛查中国专家共识中，也建议对携带 BRCA2基因突变且年龄>40岁的成年男性行前列腺 癌早期筛查[12]。Liang等[13]对 100名汉族人 DNA 进行 了全外显子组基因测序 （whole exome sequencing， WES），在 29%的患者中发现了 36个有害种系突变， 包括 DNA 甲基化、DNA 损伤修复 （DNA Damage Repair，DDR）以及酪氨酸-蛋白激酶途径等。此外还 发现了12个非DDR的新型潜在易感基因（ADGRG1、 CHD4、 DNM T3A、 ERBB3、 GRHL1、HMBS， LDLR、MYH7、MYO6、NT5C2、NUP98 和 SUGCT），这些潜在的靶点基因为未来前列腺癌的个体化 治疗提供了新思路。 单核苷酸多态性 （single nucleotide polymorphism，SNP） 也与前列腺癌密切相关，前列腺癌全 基因组关联分析 （genome- wide association study， GWAS） 发 现 了 77 个 SNP 与 前 列 腺 癌 相 关 [14]。 9q31.2 （rs817826） 跟 19q13.4 是两个与中国前列腺 癌患者相关性最强的 SNP[15]。Yasmine等[16] 对比分析 186 例前列腺癌患者及 180 名前列腺增生患者后发 现，HSD3B1基因 （rs33937873、rs6203） 是前列腺 癌的潜在影响因素 （OR：2.7，95% CI：1.2~5.5， P=0.01；OR：1.8，95% CI：1.3~2.4，P=0.0003）。 HSD3B1 可抑制泛素化和蛋白酶降解，促使大量睾 酮及二氢睾酮在细胞内积累，从而引起前列腺组织 的癌变。
众所周知，探究前列腺癌的影响因素对未来前 列腺癌的防治意义深远。近些年，越来越多的研究 开始聚焦于前列腺癌的相关危险因素。通过对既往 文献总结我们发现，尽管人们做了大量研究，目前 比较明确的影响因素仅有年龄、种族及家族遗传 史。其他影响因素譬如饮酒、肥胖、炎症、膳食结 构、环境等与前列腺癌的关系仍不是很明确，部分 临床研究甚至得出了相互矛盾的结论。此外前列腺 癌相关危险因素的研究已经从个体水平发展为分子 水平。因此，在以后的研究中，我们不仅需要大样 本多中心的前瞻性研究来探究前列腺癌的相关影响 因素，更需要从分子水平出发，譬如基因组学、蛋 白组学、代谢组学等方面探究前列腺癌的相关危险 因素。
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