Genetic variations in apoptosis pathway and the risk of ovarian cancer

Hui Xie; Wade Tao; Xifeng Wu; Jian Gu

doi:10.18632/oncotarget.10772

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Research Papers:

Genetic variations in apoptosis pathway and the risk of ovarian cancer

Hui Xie, Wade Tao, Xifeng Wu and Jian Gu _

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Oncotarget. 2016; 7:56737-56745. https://doi.org/10.18632/oncotarget.10772

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Abstract

Hui Xie1,2, Wade Tao2, Xifeng Wu2, Jian Gu2

1Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

2Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence to:

Jian Gu, email: [email protected]

Keywords: single nucleotide polymorphism, apoptosis pathway, ovarian cancer, risk

Received: May 05, 2016 Accepted: June 09, 2016 Published: July 22, 2016

ABSTRACT

Background: Apoptosis is a highly conserved form of cell death and aberrant regulation of apoptotic cell death mechanisms leads to variety of major human diseases, especially tumor formation. Genetic variations in apoptosis genes may increase susceptibility to ovarian cancer.

Results: In individual SNP analysis, 12 SNPs in 5 apoptosis pathway genes were significantly associated with ovarian cancer risk after adjustment for multiple comparisons at q-value <0.05. The most significant SNP was rs11152377 in the Bcl-2 gene. The homozygous variant TT genotype was associated with a significantly decreased risk of ovarian cancer (odds ratio [OR] =0.53; 95% confidence interval [CI], 0.37-0.77, P<0.001). Cumulative effect analysis showed joint effects of increased risk of ovarian cancer with increasing number of unfavorable genotypes in patients. Classification and regression tree (CART) analysis further revealed high-order gene-gene interactions and categorized the study subjects into low-, medium-, and high-risk groups. Compared with the low-risk group, medium-risk group and high-risk group conferred 1.76-fold (95% CI: 1.06–2.90) and 3.64-fold (95% CI: 2.37–5.59) increased risk of ovarian cancer (P for trend <0.001)

Materials and Methods: In a case-control study of 417 ovarian cancer patients and 417 matched controls, we evaluated the associations of 587 single nucleotide polymorphisms (SNPs) from 65 genes of the apoptosis pathway with the risk of ovarian cancer.

Conclusions: Our results suggest that genetic variations in apoptosis pathway genes modulate the risk of ovarian cancer individually and jointly.

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Research Papers:

Genetic variations in apoptosis pathway and the risk of ovarian cancer

Abstract