Abstract
BackgroundWe identified rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C gene polymorphisms of SERPINB5 (mammary serine protease inhibitor) that are specific to patients with oral cancer susceptibility and their clinicopathological status.Methodology/Principal findingsIn total, 1342 participants, including 601 healthy controls and 741 patients with oral cancer, were recruited for this study. Allelic discrimination of rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C of the SERPINB5 gene was assessed by a real-time PCR with a TaqMan assay. We found that individuals carrying the polymorphic rs17071138 and rs8089104 are more susceptible to oral cancer (OR, 1.57; 95% CI, 1.07~2.31 and OR, 1.58; 95% CI, 1.04~2.39, respectively). Among oral cancer-related risk factor exposures, the individuals carrying the polymorphic rs17071138 had 4.26- (95% CI: 1.65~11.01; p = 0.002), 2.34- (95% CI: 1.19~4.61; p = 0.01), and 2.34-fold (95% CI: 1.38~3.96; p = 0.001) higher risks of developing oral cancer.ConclusionsHeterozygous TC of the SERPINB5 rs17071138 polymorphism may be a factor that increases susceptibility to oral cancer. Interactions of gene-to-gene and gene-to-oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.
Highlights
SERPINB5, a 42-kDa cytoplasmic protein that belongs to the serine family of protease inhibitors is expressed in normal human mammary epithelial cells and has a protective role in the oncogenic process by inhibiting cell proliferation, development, invasion, angiogenesis, and metastasis [1,2,3,4,5,6,7].Oral cancer is one of the most common malignancies in the world [8]
It was reported that repression of premalignant cell proliferation can be triggered by oncogene-induced senescence (OIS), and SERPINB5 was suggested to be an effector of oncogene-induced senescence, which acts as a natural barrier against transformation from a premalignant lesion to carcinoma in oral leukoplakia with dysplasia [12]
The individuals who are heterozygous for a rs17071138 TC polymorphism and with CC homozygotes of the SERPINB5 rs8089104 polymorphism had 1.57- and 1.58-fold greater risks of developing oral cancer, respectively, compared to those with wild-type homozygotes of SERPINB5 rs17071138 TT and SERPINB5 rs8089104 TT after adjusting for confounding factors
Summary
SERPINB5 (a mammary serine protease inhibitor), a 42-kDa cytoplasmic protein that belongs to the serine family of protease inhibitors (serpins) is expressed in normal human mammary epithelial cells and has a protective role in the oncogenic process by inhibiting cell proliferation, development, invasion, angiogenesis, and metastasis [1,2,3,4,5,6,7].Oral cancer is one of the most common malignancies in the world [8]. SERPINB5 (a mammary serine protease inhibitor), a 42-kDa cytoplasmic protein that belongs to the serine family of protease inhibitors (serpins) is expressed in normal human mammary epithelial cells and has a protective role in the oncogenic process by inhibiting cell proliferation, development, invasion, angiogenesis, and metastasis [1,2,3,4,5,6,7]. A loss of SERPINB5 expression was correlated with an increased invasive potential in a human oral squamous cell carcinoma (OSCC) cell line [1, 4]. Tumor cells lacking SERPINB5 expression tend to have lymph node metastasis and invasive progression of OSCC, and patients with high levels of SERPINB5 gene expression have better survival rates than those with low expression levels of SERPINB5 [1, 2, 4]. We identified rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C gene polymorphisms of SERPINB5 (mammary serine protease inhibitor) that are specific to patients with oral cancer susceptibility and their clinicopathological status
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