Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: Results from the colon cancer family registry
Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: Results from the colon cancer family registry
复制标题
DOI：
10.1158/0008-5472.can-07-3239
复制
发表时间：
2007-12-01
期刊：
影响因子：
11.2
通讯作者：
Le Marchand, Loic
中科院分区：
文献类型：
--
作者：
Poynter, Jenny N.;Figueiredo, Jane C.;Le Marchand, Loic
最近的出版物报道了8q24的常见变异与前列腺癌和结直肠癌（CRC）有关。此外，其中一项研究（北极研究）最初观察到与9p24上的单核苷酸多态性（SNP）有关，但在一些验证数据集中未得到证实。在本文描述的研究中，我们使用来自结肠癌家族登记处（Colon CFR）的基于人群和临床的不一致兄弟姐妹（N = 1567名兄弟姐妹）进行了病例未影响的兄弟姐妹分析，以调查9p24和8q24常见变异与CRC风险之间的关系。我们还评估了这些关联是否因年龄、家族史和肿瘤特征（包括微卫星不稳定性和肿瘤部位）而异。使用条件逻辑回归估计关联，将兄弟姐妹作为匹配因素。分析根据年龄和性别进行调整，并根据确定的来源（人群与诊所）进行分层。在基于人群的研究中，我们观察到9p24 (rs719725) SNP与结直肠癌风险之间存在关联（AA与CC：比值比为1.46；95%可信区间为1.06-2.02；AC与CC：比值比为1.50；95%可信区间为1.14-1.98；2 df时P = 0.011）。在基于人群的序列中，我们还发现8q24上的两个snp rs10505477和rs6983267与CRC风险之间存在统计学意义上的相关性（P = 0.005和P = 0.002）。在诊断年龄、CRC家族史、微卫星不稳定性或任一位点的肿瘤部位方面，没有统计学上显著的异质性证据，也没有证据表明8q24和9p24上的snt之间存在相互作用。这些数据表明，常见变异可能在结直肠癌的风险中起重要作用。
Recent publications have reported that common variants on 8q24 are associated with both prostate and colorectal cancers (CRC). In addition, one of these studies (the ARCTIC study) initially observed an association with a single nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their validation data sets. In the research described here, we conducted a case-unaffected sibling analysis using population- and clinic-based discordant sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR) to investigate the associations between common variants at 9p24 and 8q24 and risk of CRC. We also evaluated whether these associations differed by age, family history, and tumor characteristics, including microsatellite instability and tumor site. Associations were estimated using conditional logistic regression, treating sibship as the matching factor. Analyses were adjusted for age and sex, and stratified by ascertainment source (population versus clinic). We observed an association between a SNP on 9p24 (rs719725) and risk of CRC in the population-based series (AA versus CC: odds ratios, 1.46; 95% confidence interval, 1.06-2.02; AC versus CC: odds ratios, 1.50; 95% confidence interval, 1.14-1.98; P = 0.011 on 2 df). In the population-based series, we also detected statistically significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of statistically significant heterogeneity by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locus and no evidence of interaction between SNTs on 8q24 and 9p24. These data suggest that common variants may play important roles in the risk of CRC.