Association Of Genetic Polymorphisms In Cdh1 And Ctnnb1 With Breast Cancer Susceptibility And Patients' Prognosis Among Chinese Han Women
PLOS ONE(2015)
摘要
This study aims to investigate whether the germline variants in CDH1 and CTNNB1 would affect breast cancer susceptibility and patients' prognosis among Chinese Han women using a haplotype-based association analysis. We genotyped 12 haplotype-tagging single nucleotide polymorphisms (htSNPs) in CDH1 and CTNNB1 among 1,160 BC cases and 1,336 age-matched cancer-free controls using the TaqMan (R) Genotyping Assay. For association analyses of germline variants with breast cancer susceptibility, the results showed that rs7200690, rs7198799, rs17715799, rs13689 and diplotype CGC/TGC (rs7200690 + rs12185157 + rs7198799) in CDH1 as well as rs2293303 in CTNNB1 were associated with increased breast cancer risk. In addition, the Generalized Multifactor Dimensionality Reduction (GMDR) and logistic regression analysis predicted an interaction on breast cancer risk between rs17715799 and rs13689 as well as rs13689 and menarche-FFTP (First Full-Term Pregnancy) interval. For survival analyses, the results demonstrated that the minor allele homozygotes of rs13689 and haplotype TGC in CDH1 were linked with unfavorable event-free survival of breast cancer, whereas, rs4783689 of CDH1 showed the opposite effect under dominant model. Notably, the stratified analysis revealed that rs7186053 was associated with favorable event-free survival among patients with estrogen receptor (ER)-positive, progesterone receptor (PR)-positive or lymph node metastasis negative patients. Moreover, rs7200690 and rs7198799 in CDH1 as well as rs4533622 in CTNNB1 were associated with worse event-free survival among patients with clinical stage 0-I tumors. This study indicated that the genetic polymorphisms of CDH1 and CTNNB1 were associated with breast cancer susceptibility and patients' prognosis.
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Cancer Risk
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