Common polymorphisms in D12S1034 flanking genes RASSF8 and BHLHB3 are not associated with lung adenocarcinoma risk
Common polymorphisms in D12S1034 flanking genes RASSF8 and BHLHB3 are not associated with lung adenocarcinoma risk
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DOI：
10.1016/j.lungcan.2006.11.008
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发表时间：
2007-04-01
期刊：
影响因子：
5.3
通讯作者：
Dragani, Tommaso A.
中科院分区：
文献类型：
--
作者：
Falvella, F. Stefania;Spinola, Monica;Dragani, Tommaso A.
D12 S1034与肺腺癌（ADCA）风险之间的相关性[Yanagitani N，Kohno T，Sunaga N，et al. Localization of a human lung adenocarcinoma susceptibility locus，possibly syntenic to the mouse Pas 1 locus，in nearby of the D12 S1034 locus on chromosome 12p11.2-p12.1.致癌作用。二○ ○二年; 23：1177-83]促使我们在肺ADCA和健康对照受试者中进行病例对照研究，以测试D12 S1034侧翼基因RASSF 8和BHLHB 3中单核苷酸多态性（SNP）的可能参与，其与D12 S1034的最小距离类似于16-24 kb。RASSF 8含有RAS相关结构域，是一种候选的肿瘤抑制因子，而BHLHB 3是一种含有碱性螺旋-环-螺旋结构域的蛋白质，起转录抑制因子的作用。我们观察到RASSF 8（3 '-UTR中的rs 1546550和3个内含子SNP）和BHLHB 3（3'-UTR中的Ala 298 Val和rs 1048155）中的常见SNP与肺ADCA风险之间没有显著关联。然而，携带一个或两个BHLHB 3 Val 298变异拷贝的患者组（即，Ala/瓦尔或瓦尔/瓦尔基因型）与携带Ala/Ala基因型的患者相比，短期存活者的比例更高（风险比，1.8; 95%置信区间，1.2-2.7）。在一个独立的挪威肺癌人群中进行的一项多癌组织型的复制研究未能复制BHLHB 3 Ala 298 Val与生存率的显著相关性;然而，这种相关性仅通过两个人群的ADCA分析得到证实。我们的研究结果表明，BHLHB 3变异可能会影响肺ADCA预后。(c)2006爱思唯尔爱尔兰有限公司rights reserved.
The reported association between D12S1034 and lung adenocarcinoma (ADCA) risk [Yanagitani N, Kohno T, Sunaga N, et al. Localization of a human lung adenocarcinoma susceptibility locus, possibly syntenic to the mouse Pas1 locus, in the vicinity of the D12S1034 locus on chromosome 12p11.2-p12.1. Carcinogenesis. 2002;23:1177-83] prompted us to carry out a case-control study in lung ADCA and healthy control subjects to test possible involvement of single-nucleotide polymorphisms (SNPs) in D12S1034 flanking genes RASSF8 and BHLHB3, whose minimal distances from D12S1034 are similar to 16-24 kb. RASSF8 contains a RAS-associated domain and is a candidate tumor suppressor, whereas BHLHB3 is a basic helix-loop-helix domain-containing protein that functions as a transcriptional repressor. We observed no significant association between common SNPs in RASSF8 (rs1546550 in the 3'-UTR and 3 intronic SNPs) and BHLHB3 (Ala298Val and rs1048155 in the 3'-UTR) with lung ADCA risk. However, patient groups carrying one or two copies of the BHLHB3 Val298 variation (i.e., Ala/Val or Val/Val genotypes) had a higher proportion of short-term survivors (hazard ratio, 1.8; 95% confidence interval, 1.2-2.7) compared with those carrying the Ala/Ala genotype. A replication study in an independent Norwegian lung cancer population of multiple cancer histotypes failed to replicate the significant association of BHLHB3 Ala298Val with survival; such association, however, was confirmed by analysis of ADCA only from both populations. Our results suggest that BHLHB3 variants may affect lung ADCA prognosis. (c) 2006 Elsevier Ireland Ltd. All. rights reserved.