Effects of genetic polymorphisms in INTS10 and their interaction with environmental factors on progression from persistent HBV infection to hepatocellular carcinoma

Abstract

Genome‐wide association study recently identified a novel antiviral gene INTS10 (index rs7000921) in suppression of hepatitis B virus (HBV) replication. However, data were lacking on single nucleotide polymorphisms (SNPs) of INTS10 in the context of hepatocellular carcinoma (HCC) induced by HBV infection. Herein, we conducted a case‐control study, including 737 HBV‐related HCC cases and 750 persistently HBV‐infected controls, to investigate the effect of INTS10 SNPs and their gene–environment interactions on HBV‐related HCC. In multivariate analysis, the CT genotype of rs7000921 conferred a decreased risk of HBV‐related HCC compared to the TT genotype (adjusted odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64–0.98, p for permutation test = .038). Among the 12 tagSNPs, the rs4268139 yielded a borderline significant association with disease risk under the additive model (adjusted OR = 0.80, 95% CI = 0.63–1.00, p for permutation test = .061). Random forest model further suggested the rs7000921 and rs7822495 as the two‐top ranked important SNPs, and thus a weighted genetic risk score (wGRS) was generated from these two SNPs plus rs4268139. The highest tertile of wGRS was associated with an increased risk, with an adjusted OR of 1.36 (95% CI = 1.05–1.75, p for permutation test = .016) compared to the lowest wGRS. Furthermore, an additive interaction was seen between wGRS and drinking (attributable proportion due to interaction [AP] = 0.21, 95% CI = 0.02–0.43, p = .016). The additive interaction between wGRS and smoking approached near significance (AP = 0.15, 95% CI = 0.00–0.32, p = .045). INTS10 polymorphisms may contribute to the progression from HBV infection to HCC. More importantly, INTS10 polymorphisms interact with drinking and smoking to affect the progression.

Comprehensive analysis of INTS family related to expression, prognosis, diagnosis and immune features in hepatocellular carcinoma

“…However, in colorectal cancer, INTS6 was found higher expression in cancer tissues and it promoted the growth of tumor cells by facilitating G1/S cell cycle transition [ 11 ]. Other INTS family members also contribute to cancer progression; for example, INTS3 has been shown to promote HCC development [ 12 ], and genetic polymorphisms in INTS10 are implicated in the progression from persistent hepatitis B virus (HBV) infection to HCC [ 13 ]. Moreover, INTS8 has been found to accelerate HCC cell growth by upregulating the TGF-β signaling pathway [ 14 ].…”

Early essential newborn care for cesarean section newborns in China: study protocol for a multi-centered randomized controlled trial

“…Deaths before 5 years of age have been estimated to 5.3 million globally in 2018, 47% of which occurred in the neonatal period (the first 28 days of life) [1]. In China, the neonatal mortality rate has been estimated at 4.5‰, accounting for nearly half of the under-five deaths [2].…”