Gaudet Mia M, Hunter Kent, Pharoah Paul, Dunning Alison M, Driver Kristy, Lissowska Jolanta, Sherman Mark, Peplonska Beata, Brinton Louise A, Chanock Stephen, Garcia-Closas Montserrat
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Int J Cancer. 2009 Apr 1;124(7):1716-20. doi: 10.1002/ijc.23919.
Genetic variation in SIPA1, signal-induced proliferation-associated gene 1, has been proposed to be associated with aggressive breast tumor characteristics related to metastasis and worse prognosis in humans and rodents. To test this hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at -3092 (A<G, rs931127), exon 3-135 (C>T, rs3741378), and exon 14 + 14 (C>T, rs746429), and examined them in relation to breast cancer risk and overall survival, stratified by tumor characteristics in 2 independent case-control studies conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases, 2,257 controls). Vital status (n = 396 deaths) was available for 911 Polish and 1,919 British breast cancer cases with an average follow-up time of 5.5 years. Overall, we found no significant associations between genetic variants of SIPA1 SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals (CI): rs931127-0.99, 0.93-1.06; rs3741378-1.03, 0.94-1.13; and, rs74642-0.98, 0.92-1.04). In both studies, SIPA1 polymorphisms were not related to overall mortality (per allele hazard ratios, 95% CI: 1.02, 0.88-1.17; 0.90, 0.72-1.11; 1.04, 0.90-1.21, respectively). Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival.
信号诱导增殖相关基因1（SIPA1）的基因变异被认为与人类和啮齿动物中与转移相关的侵袭性乳腺肿瘤特征以及较差的预后有关。为了验证这一假设，我们对位于-3092（A<G，rs931127）、外显子3-135（C>T，rs3741378）和外显子14 + 14（C>T，rs746429）的3个单核苷酸多态性（SNP）进行了基因分型，并在波兰（1995例病例，2296例对照）和英国（2142例病例，2257例对照）进行的2项独立病例对照研究中，根据肿瘤特征对它们与乳腺癌风险和总生存期的关系进行了研究。911例波兰乳腺癌病例和1919例英国乳腺癌病例的生命状态（n = 396例死亡）可查，平均随访时间为5.5年。总体而言，我们发现SIPA1 SNP的基因变异与乳腺癌风险之间无显著关联（每个等位基因的优势比，95%置信区间（CI）：rs931127为0.99，0.93 - 1.06；rs3741378为1.03，0.94 - 1.13；rs74642为0.98，0.92 - 1.04）。在两项研究中，SIPA1多态性均与总死亡率无关（每个等位基因的风险比，95% CI分别为：1.02，0.88 - 1.17；0.90，0.72 - 1.11；1.04，0.90 - 1.21）。我们的结果不支持SIPA1多态性与乳腺癌风险或后续生存期之间存在关联。
