Noci S, Dugo M, Bertola F, Melotti F, Vannelli A, Dragani T A, Galvan A
Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Pharmacogenomics J. 2016 Apr;16(2):173-9. doi: 10.1038/tpj.2015.35. Epub 2015 May 12.
We investigated the possible influence of 86 single-nucleotide polymorphisms (SNPs), known to associate with the risk of colorectal cancer (CRC), on overall survival and time to recurrence (TTR) in 733 Italian CRC patients followed up for up to 84 months after surgery. In the Cox multivariate analysis, adjusted for gender, age, pathological stage and adjuvant chemotherapy (yes/no), the risk of death significantly increased by rare allele count (P<0.05) for rs1801133 (MTHFR), rs4939827 (SMAD7), rs2306283 (SLCO1B1) and rs12898159 (BMP4), whereas for rs736775 (GPX3) the opposite was observed. Two additional SNPs associated with TTR, namely rs16892766 (downstream of EIF3H) and rs10749971 (COLCA2). Our findings show that some genetic variants previously found to associate with CRC risk are also associated with survival after treatment. The identification of alleles defining subgroups of patients with worse clinical outcome may have application in developing pharmacogenetic strategies aimed at personalizing CRC treatment.
我们调查了已知与结直肠癌（CRC）风险相关的86个单核苷酸多态性（SNP）对733例意大利CRC患者总生存期和复发时间（TTR）的可能影响，这些患者术后随访长达84个月。在Cox多变量分析中，校正性别、年龄、病理分期和辅助化疗（是/否）后，rs1801133（MTHFR）、rs4939827（SMAD7）、rs2306283（SLCO1B1）和rs12898159（BMP4）的罕见等位基因计数使死亡风险显著增加（P<0.05），而rs736775（GPX3）则观察到相反情况。另外两个SNP与TTR相关，即rs16892766（EIF3H下游）和rs10749971（COLCA2）。我们的研究结果表明，一些先前发现与CRC风险相关的基因变异也与治疗后的生存相关。确定定义临床结局较差患者亚组的等位基因可能有助于制定旨在使CRC治疗个性化的药物遗传学策略。
