A Case-Control Study On The Association Between Empirical Dietary Index For Insulin Resistance With Primary Liver Cancer

Objective:The occurrence of primary liver cancer is the sixth in the cancer spectrum and death is the second in the cancer spectrum.Lifestyle interventions such as diet as an important means of primary liver cancer prevention.Previous studies have shown that insulin resistance plays an important role in the disease progression of primary liver cancer,and diet can regulate the level of insulin resistance.Therefore,this study hypothesized that diet could influence primary liver carcinogenesis through the mechanistic pathway of insulin resistance.To test the hypothesis,this study intends to construct a new insulin-resistant dietary pattern empirical dietary index for insulin resistance（EDIR）that reflects the level of insulin resistance in humans,and to evaluate the association of EDIR with liver cancer in a case-control study.Methods:The EDIR construction and validation population was derived from a large-scale community-based cross-sectional survey in Anhui province.The construction set was selected from the cross-sectional survey site in Huoshan County,and the verification set was selected from the cross-sectional survey site in Shucheng County,The food frequency questionnaire was used to investigate the frequency and intake of each food item.In the control group,41 items of food or food groups were included as independent variables,and the ratio of triglyceride and high-density lipoprotein cholesterol（TG:HDL-C）was used as the response variable of insulin resistance.Down-rank regression and stepwise linear regression were used to construct EDIR.A higher EDIR score indicates a higher adherence to this dietary pattern.To evaluate the ability of EDIR to predict the level of insulin resistance,linear regression was used to calculate the relative concentration relationship between TG:HDL-C.This association study between EDIR and hepatocarcinogenesis used a case-control design.The case group was from patients with new primary liver cancer in the Anhui multicenter digestive cancer cohort,and the control group was obtained from patients with no history of chronic liver disease and normal liver function in a community-based cross-sectional survey in Anhui province.The diagnosis of primary liver cancer was based on the Standards for the Diagnosis and Treatment of Primary Liver Cancer（2019 edition）issued by the National Health Commission of the People’s Republic of China.Conditional Logistic regression was used to estimate the odds ratio（OR）and 95%confidence interval（95%CI）between EDIR scores and primary liver cancer risk.The increment of each EDIR score per standard deviation（SD）was included as a continuous variable in the model to test the linear trends.To reduce the effect of measurement error on the results of the analysis,a sensitivity analysis was performed on the EDIR score using the nutrient residual method.Furthermore,to evaluate the effect of each food component in the dietary pattern on primary liver cancer,the association of each additional SD in food intake with the risk of primary liver cancer was calculated using linear regression.Results:The EDIR contains 6 food items and food groups in the construct set.Food groups positively correlated with individual insulin resistance levels:other aquatic products,refined grains,frying,fungi and algae,and food groups negatively correlated with individual insulin resistance levels were fruit and soy drinks.Validation:Linear regression of the association between EDIR scores and TG:HDL-C in the validation set showed that the insulin resistance level（TG:HDL-C）in the highest tertile increased19%(OR=1.19,95%CI:1.04-1.37,P _trend<0.025)over the lowest EDIR scores,indicating that EDIR scores can better predict insulin resistance levels.In the case-control study of the relationship between EDIR and primary liver cancer,310 people from case group and control group were included.Among them,252（81.7%）were male and 58（18.7%）were female,aged 59.49±10.13 years old.After adjusting for confounding factors such as marital status,education status,annual household per capita income,alcohol status,physical activity,BMI,hypertension,diabetes mellitus,and total energy intake、HBV,conditional logistic regression showed that the odds ratio of primary liver cancer in the highest tertile was 1.49(OR=1.49,95%CI:0.39-5.70,P _trend=0.608),but not statistically significant.In the sensitivity analysis,the association between residual-adjusted EDIR scores and the risk of primary liver cancer was not significantly altered(OR=3.48,95%CI:0.76-16.00,P _trend=0.614).We found that no association between EDIR-related food components and the development of primary liver cancer was found.Conclusion:This study constructed dietary patterns which could reflect the level of insulin resistance in humans based on reduced-rank regression.This dietary pattern score（EDIR score）is a good predictor of insulin resistance in the body.The results of this study found that higher EDIR scores were associated with an increased risk of primary liver cancer,but we found no association of EDIR scores with the occurrence of primary liver cancer after adjusting for HBV infection.This study helps inform the development of dietary guidance for the development of primary liver cancer.