Elevated serum triglyceride levels may be a key independent predicting factor for gallbladder cancer risk in gallbladder stone disease patients: a case–control study

Abstract

Background Gallbladder stone diseases (GSD) is a main risk factor of gallbladder cancer (GBC). This study aimed to reveal their bridge to metabolic syndrome. Material/method The clinical and experimental data of 2210 GBC patients, from 3524 Chinese patients, in our hospital from Jan. 2009 to Dec. 2020 were summarized. The metabolic syndrome indexes, influencing factors for both GBC and GSD, were analyzed by unconditional logistic regression in this case–control study. Result There were significantly higher morbidity of GBC in the overall, GSD and non-GSD with hypertriglyceridemia patients versus non-hypertriglyceridemia ones (P < 0.001, all). In GSD patients, univariate regression showed a significantly positive correlation between serum triglyceride (TG), low density lipoprotein cholesterol (LDL-c), fasting insulin (FINS) levels, Homeostasis model assessment-insulin resistance (HOMA-IR), female being, body mass index, hypertriglyceridemia and hazard of GBC with GSD (P < 0.001, all), and a significantly negative correlation to systolic pressure (SBP), diastolic pressure (DBP), hypertension and high-density lipoprotein cholesterol (HDL-c), fasting blood glucose (FBG) (P < 0.05, all); multivariate regression showed that serum triglyceride was the most significantly positive factor associated to GBC (P < 0.001, all) among the hazard factors including serum TG, LDL-c levels, HOMA-IR. In non-GSD ones, multivariate regression showed that HOMA-IR was the most significantly positive factor associated to GBC among the hazard factors including serum TG, LDL-c levels, HOMA-IR, female being, while DM had a significantly inversion negative association (P < 0.001). Conclusion We found initially that elevated serum TG levels could be the most remarkable independent predicting factor for GBC risk with GSD, while insulin resistance might act as the first one in non-GSD. More importantly, we advocated initially the sharp rise of serum TG levels as the potential of a candidate diagnostic or prognostic biomarker of GBC with GSD. Trial registration The study may be performed in accordance with the ethical standards provided by the responsible committee of our institution (First Affiliated Hospital of Xi’an Jiaotong University. XJTU1AF2020LSK-160) at which the work was carried out an in accordance with the Declaration of Helsinki. The ethics committee of our institution strictly comply with the requirements of ICH-GCP、GCP and relevant regulations to construct, operate and implement operating procedures.

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses

“…Although molecular interactions between LDL-C and stomach cancer among participants aged 60 years or older have not been ascertained, we could speculate that estrogen benefits female participants by anti-inflammatory properties [ 38 ], as well as suppressing proliferation and promoting apoptosis of gastric cancer cells [ 39 ]. What’s more, with regard to gallbladder cancer, a previous observational analysis preliminarily revealed that elevated TG concentration was independently positively correlated with the high risk of gallbladder cancer [ 35 ], which was consistent with our study. Despite the fact of insufficient MR evidences to support the linear causal effect of TG concentration on the risk of gallbladder cancer, the category of TG ≥ 2.2 mmol/L could be perceived as the robust risk biomarker for male participants and participants aged 60 years or older with sufficient phenotypic and stratified MR evidences.…”

“…A meta-analysis showed that HDL-C and TG concentrations were independently correlated with the risk of colorectal cancer in linearly positive and negative manners [ 9 ]. TG concentration has been reported as an independent risk factor for gallbladder cancer in Chinese populations [ 35 ]. Though our study extended primary observational results to phenotypic pattern evidences, and supported remarkable independent linear associations between HDL-C and the risk of stomach cancer, suggestive independent linear associations between HDL-C and the risk of colorectal cancer, and between TG concentration and the risk of gallbladder cancer, nonlinear and linear MR-based evidences with non-confounding interferences determined no genetic associations between them.…”

“…Table 1 shows statistical comparisons of signature lipidomic biomarkers and demographic characteristics between participants with and without DSCs. Median HDL-C and LDL-C concentrations were significantly lower in participants with DSCs than in those without DSCs (1.358 vs. 1.410 mmol/L, 3.508 vs. 3.536 mmol/L, P trend < 0.001), whereas a significant opposite tendency was observed for median TG concentration (1.621 vs. 1.478 mmol/L, P trend < 0.001), age (62.000 vs. 58.000 years, P trend = 0.000), BMI (27.367 vs. 26.638 kg/m 2 , P trend < 0.001), TDI (-2.283 vs. -2.305, P trend = 0.023), ALT (24.900 vs. 24.300 U/L, P trend < 0.001), AST (20.740 vs. 19.990 U/L, P trend < 0.001), SBP (143.000 vs. 138.000 mmHg, P trend < 0.001), DBP (83.000 vs. 82.000 mmHg, P trend < 0.001), and HbA1c (36.050 vs. 35.100 mmol/mol, P trend < 0.001). Meanwhile, DSCs were more common in male participants, previous or current smokers, never or previous alcohol drinkers, none-employed participants, and participants taking given medications, lacking physical activity, as well as with cerebral infarction, ischaemic heart disease, primary hypertension, diabetes, and family cancer history.…”

Biomarker Discovery for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Using Untargeted Metabolomics and Lipidomics Studies

“…The increased levels of circulatory TGs are a well-known biomarker of liver dysfunction and are reported to have a positive correlation with multiple liver diseases, including cholestasis, ALD, NAFLD, HBV, and HCC [39]. Higher levels of TG are also found in numerous other cancers like gallbladder, cervical, colon, and respiratory cancers [40], while a few studies have reported a negative correlation of TG with prostate and breast cancers [41,42]. According to Liu et al, TG upregulation was observed in HCC patients who had no cirrhosis [43].…”