A common 8q24 variant in prostate and breast cancer from a large nested case-control study
A common 8q24 variant in prostate and breast cancer from a large nested case-control study
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DOI：
10.1158/0008-5472.can-06-3591
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发表时间：
2007-04-01
期刊：
影响因子：
11.2
通讯作者：
Hunter, David J.
中科院分区：
文献类型：
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作者：
Schumacher, Fredrick R.;Feigelson, Heather Spencer;Hunter, David J.
最近的两项研究独立地发现了8q24区域的多态，包括单核苷酸多态(Rsl447295)，与前列腺癌风险密切相关。在这里，我们复制了来自国家癌症研究所乳腺癌和前列腺癌队列联合会的一项大型嵌套病例对照研究中的总体关联，该研究使用了6637例前列腺癌病例和7361例匹配对照。我们还在2,604例高加索人乳腺癌病例和3,118名匹配对照中检验了该基因多态是否与乳腺癌有关。在高加索人群中，rs1447295标记与前列腺癌密切相关(P=1.23×10(-13))。当我们排除Freedman等人以前报告的多种族队列样本时，这种相关性仍然非常显著(P=8.64×10(-13))。与野生型纯合子相比，携带一个小等位基因的携带者ORAC=1.34(99%可信区间1.19-1.50)，携带两个小等位基因的携带者ORAC=1.86(99%可信区间1.30-2.67)。在非裔美国人中，在早期被诊断为前列腺癌的男性中，这种基因关联具有统计学意义(P=0.011)，而在较晚被诊断为前列腺癌的男性中，这种关联没有统计学意义(P=0.924)。在高加索人中，确诊时不同年龄的风险差异不存在。我们发现，当肿瘤按Gleason评分、分期或死亡率进行分类时，风险没有统计学上的显著差异。我们发现rs1447295与乳腺癌风险没有关联(P=0.590)。尽管导致前列腺癌的基因尚未确定，但这一标记在前列腺癌大样本中的验证几乎没有留下假阳性结果的可能性。
Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rsl447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 X 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an ORAC = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an ORAA = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result.