Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, whose diversified occurrence worldwide indicates a connection between genetic variations among individuals and the predisposition to such neoplasms. Mounting evidence has demonstrated that long non-coding RNA (lncRNA) H19 can have both promotive and inhibitory effects on cancer development, revealing a dual role in tumorigenesis. In this study, the link of H19 gene polymorphisms to hepatocarcinogenesis was assessed between 359 HCC patients and 1190 cancer-free subjects. We found that heterozygotes for the minor allele of H19 rs2839698 (T) and rs3741219 (G) were more inclined to develop HCC (OR, 1.291; 95% CI, 1.003–1.661; p = 0.047, and OR, 1.361; 95% CI, 1.054–1.758; p = 0.018, respectively), whereas homozygotes for the polymorphic allele of rs2107425 (TT) were correlated with a decreased risk of HCC (OR, 0.606; 95% CI, 0.410–0.895; p = 0.012). Moreover, patients who bear at least one variant allele (heterozygote or homozygote) of rs3024270 were less prone to develop late-stage tumors (for stage III/IV; OR, 0.566; 95% CI, 0.342–0.937; p = 0.027). In addition, carriers of a particular haplotype of three H19 SNPs tested were more susceptible to HCC. In conclusion, our results indicate an association between H19 gene polymorphisms and the incidence and progression of liver cancer.

Urothelial cell carcinoma (UCC) is one of the major malignancies of the genitourinary tract, and it is induced by carcinogenic epidemiological risk factors. H19 is one of the most crucial long noncoding RNAs (lncRNAs) and is involved in various types of bladder cancer. In this study, we examined H19 single-nucleotide polymorphisms (SNPs) to investigate UCC susceptibility and clinicopathological characteristics. Using real-time polymerase chain reaction, we analyzed five SNPs of H19 in 431 UCC patients and 431 controls without cancer. The results showed that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants had a high risk of developing muscle invasive tumors (pT2–T4) (p = 0.030; p = 0.025, respectively). With a median follow up of 39 months, CT+TT polymorphisms of rs2107425 were associated with worse disease-specific survival (adjusted hard ratio (AHR) = 2.043, 95% confidence interval (CI) = 1.029-4.059) in UCC patients aged older than 65 years. In conclusion, our results indicate that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants have a high risk of developing muscle invasive tumors. Thus, H19 polymorphisms may be applied as a marker or therapeutic target in UCC treatment.

A disintegrin and metalloprotease (ADAM) family proteins are type-I transmembrane glycoproteins with multiple functions in cell adhesion, migration, proteolysis and signaling. ADAM10 is a member of the ADAM family reportedly involved in cancer progression and has been shown to be overexpressed in hepatocellular carcinoma (HCC) tissues and significantly associated with tumor progression and shortened survival. This study investigated ADAM10's single nucleotide polymorphisms (SNPs) and their association to HCC development and regulation. Real-time polymerase chain reaction was used to analyze five SNPs of ADAM10 in 333 patients with HCC and 1196 controls without cancer. The results indicated that of the 333 patients with HCC, those who carried ADAM10 rs514049 (AC + CC) variants had a higher risk of developing lymph node metastasis (odds ratio [OR] = 5.087, p = 0.027), and those who carried ADAM10 rs653765 (GA + AA) variants had a higher risk of developing distant metastasis (OR = 3.346, p = 0.020) and higher levels of α-fetoprotein. In conclusion, our study demonstrated that the SNPs of ADAM10 are involved in HCC progression. ADAM10 SNPs may be used as therapeutic targets to evaluate poor prognoses for HCC.

Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics. Real-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis. Our results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

EGF-like domain 6 (EGFL6), a member of the epidermal growth factor (EGF) repeat protein superfamily, is a secreted protein that promotes endothelial cell migration and angiogenesis. The current study investigated the association between the clinicopathological characteristics and plasma level of EGFL6 in patients with oral squamous cell carcinoma (OSCC). We measured the plasma EGFL6 levels of 392 OSCC patients by using a commercial enzyme-linked immunosorbent assay. We also analyzed EGFL6 mRNA levels of 328 OSCC patients from The Cancer Genome Atlas (TCGA) dataset. The results showed that plasma EGFL6 levels were significantly higher in patients with OSCC than in healthy controls (p < 0.001). Similar results were observed for the TCGA bioinformatics database. Moreover, plasma EGFL6 levels were significantly higher in the patients with advanced T status (p = 0.002), distant metastasis (p = 0.001), and higher TNM stage (p=0.033). In conclusion, our results suggest that plasma level of EGFL6 may be useful to assess disease progression, and especially advanced T status and higher TNM stage in patients with OSCC.