A Functional Insertion/Deletion Polymorphism in the Promoter of PDCD6IP Is Associated with the Susceptibility of Hepatocellular Carcinoma in a Chinese Population

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Apart from environmental factors such as hepatitis B virus (HBV) or hepatitis C virus, alcohol abuse, and exposure to dietary aflatoxin, genetic factors are also involved in the pathogenesis of HCC. By analyzing 390 HCC cases and 431 healthy controls in a Chinese population, we used a candidate gene approach to evaluate the association between a 15-bp insertion/deletion (indel) polymorphism (rs28381975) in the promoter region of the programmed cell death 6 interacting protein (PDCD6IP) gene and HCC susceptibility. Logistic regression analysis demonstrated that subjects carrying ins/del or ins/ins genotypes had significantly increased risk for HCC than individuals carrying del/del genotypes (adjusted odds ratio=1.39, 95% confidence interval=1.01-1.91, p=0.033]. Carrying the 15-bp insertion allele was associated with a 1.26-fold risk for HCC (95% CI=1.04-1.54, p=0.018). Moreover, significant differences were observed within HCC patients concerning genotypic frequencies of rs28381975 after stratifying by tumor stages and HBV infection. Computational modeling suggests that rs28381975 could disrupt the binding patterns of c-rel, a key subunit of nuclear factor-kappaB transcription factor. Further luciferase-based transient transfection assays revealed that rs28381975 can affect the promoter activity of PDCD6IP, indicating its possible functional significance. Taken together, our data suggest that common genetic variations in PDCD6IP may influence HCC risk, possibly through promoter activity-mediated regulation. Replication of our studies in other populations and further functional analysis will strengthen our understanding of this association.

An integrated package for bisulfite DNA methylation data analysis with Indel-sensitive mapping

“…Insertions and deletions (indels) are the second most common type of human genetic variants after single nucleotide polymorphisms (SNP) [19]. Many human inherited diseases have been reported to be related to indels [20, 21]. Recent results show that the indel rate in the human genome is approximately 1 in 3000 bp [22].…”

Pan-Cancer Analysis Reveals the Functional Importance of Protein Lysine Modification in Cancer Development

“…Specifically, in liver cancer, we predicted 41 driver proteins that were significantly mutated at lysine modification motifs. Eight (19.5%) of these proteins were reported previously as cancer drivers (Friedenson, 2005 ; Silvera et al, 2010 ; Zhou et al, 2011 ; Chang et al, 2013 ; Yu et al, 2013 ; Pandey et al, 2016 ; Miao et al, 2017 ; Tang et al, 2017 ). In particular, HOXC10 was known to be associated with a decrease in the overall survival rate of liver cancer (Tang et al, 2017 ).…”

Association between Programmed Cell Death 6 Interacting Protein Insertion/Deletion Polymorphism and the Risk of Breast Cancer in a Sample of Iranian Population

“…To date, there have only been two reports that investigated the association between PDCD6IP 15 bp I/D and cancer risk. Yu et al [ 22 ] evaluated the possible association between the PDCD6IP 15 bp I/D polymorphism and hepatocellular carcinoma (HCC). They found that subjects carrying I/D or I/I genotype had a significantly increased risk for HCC compared to individuals carrying the D/D genotype (OR = 1.39, 95% CI = 1.01–1.91, p = 0.033).…”

“…Currently, little information is available regarding the association between PDCD6IP polymorphisms and cancer risk [ 9 , 22 ]. To the best of our knowledge, there are no reports regarding the association between the 15 bp I/D variant within the PDCD6IP promoter and BC susceptibility.…”