Relationship between functional polymorphism in the Aurora A gene and susceptibility of hepatocellular carcinoma

Abstract

Aurora A is considered a potential cancer susceptibility gene owing to overexpression or amplification of Aurora A gene that causes centrosome dysfunction, chromosome instability, tumourigenic transformation and checkpoint abnormalities. Functional coding region polymorphism F31I in the Aurora A gene has recently been shown to be associated with several human cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. Genetic polymorphism of Aurora A was investigated in 128 confirmed subjects with HCC and 128 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Allele and genotype associations of Aurora A F31I polymorphism with HCC susceptibility were observed in comparisons between the patient and control samples (respectively; P = 0.005, P = 0.012). The proportion of the genotypes containing I31 allele in patients with HCC (39.8%) was significantly higher than that in patients without HCC (22.7%) (P = 0.003). The distribution F31I genotype was significantly associated with increased risk of HCC (P = 0.003, odds ratio = 2.26, 95% confidence interval = 1.31-3.90 for FI + II genotypes vs FF genotype). Our results suggest for the first time that the Aurora A F31I polymorphism may be a genetic susceptibility factor for HCC.

Association between the STK15 F31I Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 43,626 Subjects

“…Among the 27 case-control studies, ten investigated breast cancer [8,9,14-21], four investigated colorectal cancer [10,22-24], and three investigated esophageal cancer [11,25,26]. The other studies investigated gastric cancer, lung cancer, renal cell carcinoma, bladder cancer, glioblastoma, hepatocellular carcinoma, and ovarian cancer [27-36]. As for subjects in these studies, 11 were Asian [9,11,19-21,23,25-29] and 16 were Caucasian [8,10,14-18,22,24,30-36].…”

“…The other studies investigated gastric cancer, lung cancer, renal cell carcinoma, bladder cancer, glioblastoma, hepatocellular carcinoma, and ovarian cancer [27-36]. As for subjects in these studies, 11 were Asian [9,11,19-21,23,25-29] and 16 were Caucasian [8,10,14-18,22,24,30-36]. Characteristics of populations and cancer types in each individual study recruited in the meta-analysis are listed in Table 1 .…”

No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: A case-control study

“…As in many cancers, genetic polymorphisms of the genes involved in multistage of hepatocarcinogenesis may determine an individual's susceptibility to the development of HCC (Akkız et al, 2010(Akkız et al, , 2011. The identification of SNPs that affect gene function or expression and contribute to HCC susceptibility is important as it may help to predict individual and population risk and clarify pathophysiologic mechanisms relevant to HCC.…”

“…The study population and subject characteristics were previously described elsewhere (Akkız et al, 2010(Akkız et al, , 2011. This is an ongoing molecular epidemiologic study of HCC conducted in Adana, Turkey and the subject recruitment was approved by the Committee for Ethics of Medical Experiment on Human Subjects, Faculty of Medicine, Çukurova University.…”

Physiological Relevance of Cell Cycle Kinases

“…However, perhaps the most interesting information about Aurora A and tumor development was generated in a genetic screen for skin tumor susceptibility genes in the mouse. Aurora A was identified as a low-penetrance tumor susceptibility gene in mouse and human tumors (85), and specific polymorphisms for Aurora A have been later described in multiple tumor types such as hepatocarcinoma and prostate, pancreas, colorectal, lung, gastric, breast, and esophageal cancer (5,54,61,86,160,173,199,224,230,316). A polymorphism in Aurora B may also modulate tumor outcome in breast tumor patients (322).…”