Association of breast cancer susceptibility variants with risk of pancreatic cancer.
Association of breast cancer susceptibility variants with risk of pancreatic cancer.
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DOI：
10.1158/1055-9965.epi-09-0306
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发表时间：
2009-11
期刊：
影响因子：
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通讯作者：
Petersen GM
中科院分区：
文献类型：
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作者：
Couch FJ;Wang X;McWilliams RR;Bamlet WR;de Andrade M;Petersen GM
许多易感基因是乳腺癌和胰腺癌共有的。最近，通过全基因组关联研究，已经确定了几个乳腺癌易感基因座。在这里，我们评估了这些单核苷酸多态性（SNPs）和胰腺癌风险之间的可能关联。在一项基于临床的胰腺癌病例对照研究中，对1143名患有胰腺癌的白人个体和1097名未受影响的对照进行基因分型后，研究了来自FGFR 2、TOX 3、MAP 3 K1、H19、LSP 1、染色体8 q24、CASP 8和LUM的10个SNP与胰腺癌风险的相关性。CASP 8 rs 1045485（比值比（OR）= 0.78; 95%置信区间（95%CI），0.65-0.9; p=0.005）和MAP 3 K1 rs 889312（OR= 0.85; 95%CI，0.74-0.97; p=0.017）显示与胰腺癌风险相关的证据。CASP 8 rs 1045485相关性在曾经吸烟者中明显（p=0.002），但在非吸烟者中不明显（p=0.55），并且在重度吸烟者中效果最强（OR，0.52; 95%CI，0.29- 0.93; p=0.03）。相比之下，MAP 3 K1 rs 889312相关性仅在非吸烟者中明显（OR，0.78; 95%CI，0.64-0.95; p=0.01）。此外，评估10个SNP对生存率的影响发现，局部晚期胰腺癌病例的结局与8 q rs6983561（p=0.045）和LUM rs 2268578（p=0.02）之间存在显著相关性。一项大型胰腺病例对照研究中的关联研究表明，与乳腺癌相关的SNP也可能与胰腺癌易感性和生存率相关。
A number of susceptibility genes are common to breast and pancreatic cancer. Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNPs) and pancreatic cancer risk. Ten SNPs from FGFR2, TOX3, MAP3K1, H19, LSP1, chromosome 8q24, CASP8 and LUM were investigated for associations with pancreatic cancer risk following genotyping in 1143 caucasian individuals with pancreatic adenocarcinoma and 1097 unaffected controls from a clinic-based pancreatic cancer case-control study. CASP8 rs1045485 (Odds ratio (OR)= 0.78; 95% confidence interval (95%CI), 0.65-0.9; p=0.005) and MAP3K1 rs889312 (OR= 0.85; 95%CI, 0.74-0.97; p=0.017)) showed evidence of association with risk of pancreatic cancer. The CASP8 rs1045485 association was evident in ever-smokers (p=0.002), but not in non-smokers (p=0.55), and the effect was strongest in heavy smokers (OR, 0.52; 95% CI, 0.29- 0.93; p=0.03). In contrast the MAP3K1 rs889312 association was only evident in non-smokers (OR, 0.78; 95%CI, 0.64-0.95; p=0.01). In addition, evaluation of the influence of the ten SNPs on survival detected significant associations between outcome for locally advanced pancreatic cancer cases and both 8q rs6983561 (p=0.045) and LUM rs2268578 (p=0.02). Association studies in a large pancreatic case-control study indicates that SNPs associated with breast cancer may also be associated with pancreatic cancer susceptibility and survival.