Chen Lan, Ambrosone Christine B, Lee Jihyun, Sellers Thomas A, Pow-Sang Julio, Park Jong Y
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
J Urol. 2006 Jan;175(1):108-12; discussion 112. doi: 10.1016/S0022-5347(05)00042-X.
XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks and base damage that arise from various endogenous and exogenous oxidants. We determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate cancer.
We performed a case-control study in 228 white American men, 124 black American men, and 335 age, sex and race matched controls. Polymorphisms at codon 399 in XRCC1, and at codons 51 and 148 in APE1 were determined using an restriction fragment length polymorphism method. Frequencies were compared between cases and controls.
A significantly increased risk of prostate cancer was observed in white men with the XRCC1(399Gln) allele (OR 1.6, 95% CI 1.1 to 2.4). When APE1 and XRCC1 polymorphisms were evaluated together, we found an increased risk of the XRCC1(399Arg/Gln+Gln/Gln)/APE1(51Gln/Gln) (OR 4.0, 95% CI 1.3 to 12.5) and XRCC1(399Arg/Gln+Gln/Gln)/APE1(148Asp/Asp) (OR 2.9, 95% CI 1.4 to 6.1) genotypes in white men. Significant associations were found between combined genotypes and prostate cancer risk with a dose-effect relationship in white men (trend test p = 0.035 and 0.039, respectively). No significant associations were observed between polymorphisms in these genes and prostate cancer risk in black men.
Our results suggest that inherited variability in DNA repair capacity, as reflected by polymorphisms in XRCC1 and APE1, is a risk factor for prostate cancer.
XRCC1和APE1是参与修复因各种内源性和外源性氧化剂导致的DNA链断裂和碱基损伤的酶。我们确定XRCC1和APE1基因多态性是否会增加前列腺癌风险。
我们对228名美国白人男性、124名美国黑人男性以及335名年龄、性别和种族匹配的对照者进行了病例对照研究。采用限制性片段长度多态性方法确定XRCC1基因第399密码子、APE1基因第51和148密码子的多态性。比较病例组和对照组的基因频率。
携带XRCC1（399Gln）等位基因的白人男性患前列腺癌的风险显著增加（比值比1.6，95%可信区间1.1至2.4）。当同时评估APE1和XRCC1基因多态性时，我们发现白人男性中XRCC1（399Arg/Gln+Gln/Gln）/APE1（51Gln/Gln）（比值比4.0，95%可信区间1.3至12.5）和XRCC1（399Arg/Gln+Gln/Gln）/APE1（148Asp/Asp）（比值比2.9，95%可信区间1.4至6.1）基因型的风险增加。在白人男性中，联合基因型与前列腺癌风险之间存在显著关联，并呈剂量效应关系（趋势检验p值分别为0.035和0.039）。在黑人男性中，未观察到这些基因的多态性与前列腺癌风险之间存在显著关联。
我们的结果表明，XRCC1和APE1基因多态性所反映的DNA修复能力的遗传变异性是前列腺癌的一个风险因素。
