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PurposeThe incidence of primary liver cancer is increasing year by year, with environmental factors playing a non-negligible role. At present, many studies are still disputing whether air pollution is associated with primary liver cancer incidence, and it is difficult to draw causal inferences. Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5–10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1).Patients and methodsWe used large-scale publicly available genome-wide association studies (GWAS) summary data to conduct MR analyses of European and East Asian populations. Inverse variance weighted (IVW) method was used as the main analysis method, and weighted median model, MR-Egger, simple model and weighted model methods were selected for quality control. Heterogeneity was checked by the Cochran’s Q test. The MR-Egger regression and the MR-PRESSO global test detect pleiotropy. The sensitivity analysis was performed using the leave-one-out method.ResultsBetween air pollution and primary liver cancer in either European (PM2.5: p = 0.993; PM2.5–10: p = 0.833; PM10: p = 0.257; nitrogen dioxide: p = 0.215; nitrogen oxides: p = 0.614) or East Asian (PM2.5: p = 0.718; PM2.5–10: p = 0.362; PM10: p = 0.720; nitrogen dioxide: p = 0.101; nitrogen oxides: p = 0.760) populations were found no statistical association. Notably, there was a causal relationship between nitrogen oxides and Arginase-1, a biomarker associated with hepatocellular differentiation, statistically significant associations remained after deletion for single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency, Body mass index (BMI) and cancers (Beta: 4.46; 95%CI: 0.83–8.08; p = 0.015). There was no heterogeneity or pleiotropy in the results.ConclusionThis MR study found no evidence to support a causality between air pollution and primary liver cancer in European and East Asian populations, but nitrogen oxides may affect hepatocellular differentiation.

BackgroundLow birth weight (LBW) is one of the most common adverse pregnancy outcomes. Previous studies have consistently shown that maternal body mass index (BMI) status before and during pregnancy is associated with LBW. However, previous studies lacked an association between paternal BMI and the conjunction effect of a couple's BMI and LBW in the offspring. Therefore, we established a cohort of pre-pregnancy couples to prospectively assess the relationship between maternal and paternal pre-pregnancy BMI and offspring LBW, very low birth weight (VLBW), and extremely low birth weight (ELBW).MethodsA prospective cohort study was established in Central China. A total of 34,104 pregnant women with singleton pregnancies at 8–14 gestational weeks and their husbands were finally enrolled and followed to 3 months postpartum. The multivariate logistic regression and restrictive cubic spline model were used to explore the relationship between parental pre-pregnancy BMI and the risk of LBW, VLBW, and ELBW in offspring.ResultsOf the 34,104 participants, maternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.720, 95% CI = 1.533 ~ 1.930; obesity: OR = 1.710, 95% CI = 1.360 ~ 2.151), VLBW (overweight: OR = 2.283, 95% CI = 1.839 ~ 2.834; obesity: OR = 4.023, 95% CI = 2.855 ~ 5.670), and ELBW (overweight: OR = 3.292, 95% CI = 2.151 ~ 5.036; obesity: OR = 3.467, 95% CI = 1.481 ~ 8.115), while underweight was associated with a higher risk of LBW (OR = 1.438, 95% CI = 1.294 ~ 1.599) and a lower risk of ELBW (OR = 0.473, 95% CI = 0.236 ~ 0.946). Paternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.637, 95% CI = 1.501 ~ 1.784; obesity: OR = 1.454, 95% CI = 1.289 ~ 1.641) and VLBW (overweight: OR = 1.310, 95% CI = 1.097 ~ 1.564; obesity: OR = 1.320, 95% CI = 1.037 ~ 1.681), while underweight was associated with a lower risk of LBW (OR = 0.660, 95% CI = 0.519 ~ 0.839). Parents who were both excessive-weights in pre-pregnancy BMI, as well as overweight mothers and normal-weight fathers before pre-pregnancy, were more likely to have offspring with LBW, VLBW, and ELBW. Dose-response relationship existed between parental pre-pregnancy and LBW, VLBW, and ELBW, except for paternal BMI and ELBW.ConclusionsParental pre-pregnancy BMI was associated with the risk of LBW in offspring. Management of weight before pregnancy for couples might help reduce their adverse pregnancy outcomes in future intervention studies.