Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Cancer Epidemiol. 2013 Oct;37(5):619-24. doi: 10.1016/j.canep.2013.06.005. Epub 2013 Jul 11.
Angiogenesis and inflammation are implicated in breast cancer prognosis; however, the role of individual germline variation in related genes is unknown.
A two-stage candidate pathway association study was conducted among 6983 Chinese women. Stage 1 included 2884 women followed for a median of 5.7 years; Stage 2 included 4099 women followed for a median of 4.0 years. Cox proportional hazards regression was used to estimate the effects of genetic variants on disease-free survival (DFS) and overall survival (OS).
Stage 1 included genotyping of 506 variants in 22 genes; analysis was conducted for 370 common variants. Nominally significant associations with DFS and/or OS were found for 20 loci in ten genes in Stage 1; variants in 19 loci were successfully genotyped and evaluated in Stage 2. In analyses of both study stages combined, nominally significant associations were found for nine variants in seven genes; none of these associations surpassed a significance threshold level corrected for the total number of variants evaluated in this study.
No association with survival was found for 370 common variants in 22 angiogenesis and inflammation pathway genes among Chinese women with breast cancer.
Our data do not support a large role for common genetic variation in 22 genes in breast cancer prognosis; research on angiogenesis and inflammation genes should focus on common variation in other genes, rare host variants, or tumor alterations.
血管生成和炎症与乳腺癌的预后有关;然而,相关基因中个体种系变异的作用尚不清楚。
在中国 6983 名女性中进行了两阶段候选途径关联研究。第 1 阶段包括 2884 名中位随访时间为 5.7 年的女性;第 2 阶段包括 4099 名中位随访时间为 4.0 年的女性。使用 Cox 比例风险回归估计遗传变异对无病生存率(DFS)和总生存率(OS)的影响。
第 1 阶段包括 22 个基因中的 506 个变异的基因分型;对 370 个常见变异进行了分析。在第 1 阶段的 10 个基因中有 20 个位点的 DFS 和/或 OS 与名义上显著相关;在第 2 阶段成功对 19 个位点的变体进行了基因分型和评估。在两个研究阶段的综合分析中,在七个基因中的九个变体中发现了名义上显著的关联;这些关联中没有一个超过本研究中评估的总变异数量校正后的显著阈值水平。
在中国乳腺癌女性中,22 个血管生成和炎症途径基因的 370 个常见变异与生存无关。
我们的数据不支持在 22 个乳腺癌预后相关基因中的常见遗传变异在 370 个常见变异中起重要作用;对血管生成和炎症基因的研究应集中在其他基因的常见变异、罕见的宿主变异或肿瘤改变上。