Mendelian randomization study of interleukin (IL)-1 family and lung cancer.
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ABSTRACT:
SUBMITTER: Yang Z
PROVIDER: S-EPMC8413403 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Family socioeconomic position (SEP) in childhood is an important factor to predict some chronic diseases. However, the association between family SEP in childhood and the risk of lung cancer is not clear. Methods A systematic search was performed to explore their relationship. We selected education level, socioeconomic positions of parents and childhood housing conditions to represent an individual family SEP. Hazard ratios (HRs) of lung cancer specific-mortality were synthesized using a random effects model. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SEP to assess the possible causal relationship of SEP and risk of lung cancer. Results Through meta-analysis of 13 studies, we observed that to compared with the better SEP, the poorer SEP in the childhood was associated with the increased lung cancer risk in the adulthood (HR: 1.25, 95% CI: 1.10 to 1.43). In addition, the dose-response analysis revealed a positive correlation between the poorer SEP and increased lung cancer risk. Same conclusion was reached in MR [(education level) OR 0.50, 95% CI: 0.39 to 0.63; P < 0.001]. Conclusion This study indicates that poor family socioeconomic position in childhood is causally correlated with lung cancer risk in adulthood. Systematic Review Registration identifier: 159082.
| S-EPMC9207765 | biostudies-literature
Project description:BackgroundObservational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method.MethodsWith a two-sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer.ResultsOur results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01-fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34-3.01; P = 7.40 × 10-4 ). Additionally, lung cancer was not a causal factor for DPA. The results of MR-Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy.ConclusionsGenetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.
| S-EPMC6488117 | biostudies-literature
Project description:Multidimensional sleep trait, which is related to circadian rhythms closely, affects some cancers predominantly, while the relationship between sleep and lung cancer is rarely illustrated. We aimed to investigate whether sleep is causally associated with risk of lung cancer, through a two-sample Mendelian randomization study. The main analysis used publicly available GWAS summary data from two large consortia (UK Biobank and International Lung Cancer Consortium). Two-sample Mendelian randomization (MR) analysis was used to examine whether chronotype, getting up in the morning, sleep duration, nap during the day, or sleeplessness was causally associated with the risk of lung cancer. Additionally, multivariate MR analysis was also conducted to estimate the direct effects between sleep traits and lung cancer risks independent of smoking status including pack years of smoking or current tobacco smoking. There was no evidence of causal association between chronotype, getting up in the morning, or nap during the day and lung cancer. Sleeplessness was associated with higher risk of lung adenocarcinoma (odds ratio 5.75, 95% confidence intervals 2.12-15.65), while sleep duration played a protective role in lung cancer (0.46, 0.26-0.83). In multivariate MR analysis, sleeplessness and sleep duration remained to have similar results. In conclusion, we found robust evidence for effect of sleeplessness on lung adenocarcinoma risk and inconsistent evidence for a protective effect of sleep duration on lung cancer risk.
| S-EPMC8238591 | biostudies-literature
Project description:BackgroundThere has been no study systematically assessing the causal effects of putative modifiable risk factors on lung cancer. In this study, we aimed to construct a modifiable risk factors atlas of lung cancer by using the two-sample Mendelian randomization framework.MethodsWe included 46 modifiable risk factors identified in previous studies. Traits with p-value smaller than 0.05 were considered as suggestive risk factors. While the Bonferroni corrected p-value for significant risk factors was set to be 8.33 × 10-4 .ResultsIn this two-sample Mendelian randomization analysis, we found that higher socioeconomic status was significantly correlated with lower risk of lung cancer, including years of schooling, college or university degree, and household income. While cigarettes smoked per day, time spent watching TV, polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid in blood were significantly associated with higher risk of lung cancer. Suggestive risk factors for lung cancer were found to be serum vitamin A1, copper in blood, docosahexaenoic acid in blood, and body fat percentage.ConclusionsThis study provided the first Mendelian randomization assessment of the causality between previously reported risk factors and lung cancer risk. Several modifiable targets, concerning socioeconomic status, lifestyle, dietary, and obesity, should be taken into consideration for the development of primary prevention strategies for lung cancer.
| S-EPMC8267159 | biostudies-literature
Project description:Interleukin-6 (IL-6) plays a contributory role in the progression and severity of many forms of cancer; it however remains unclear whether the relevance between circulating IL-6 and cancer is causal. We therefore meta-analyzed published articles in this regard using IL-6 gene -174G/C variant as an instrument. Seventy-eight and six articles were eligible for the association of -174G/C variant with cancer and circulating IL-6, respectively. Overall analyses failed to identify any significance between -174G/C and cancer risk. In Asians, carriers of the -174CC genotype had an 1.95-fold increased cancer risk compared with the -174GG genotype carriers (P = 0.009). By cancer type, significance was only attained for liver cancer with the -174C allele conferring a reduced risk under allelic (odds ratio or OR = 0.74; P = 0.001), homozygous genotypic (OR = 0.59; P = 0.029) and dominant (OR = 0.67; P = 0.004) models. Carriers of the -174CC genotype (weighted mean difference or WMD = -4.23 pg/mL; P < 0.001) and -174C allele (WMD = -3.43 pg/mL; P < 0.001) had circulating IL-6 reduced significantly compared with the non-carriers. In further Mendelian randomization analysis, a reduction of 1 pg/mL in circulating IL-6 was significantly associated with an 12% reduced risk of liver cancer. Long-term genetically-reduced circulating IL-6 might be causally associated with a lower risk of liver cancer.
| S-EPMC4476043 | biostudies-literature
Project description:The phrase "mendelian randomization" has become associated with the use of genetic polymorphisms to uncover causal relationships between phenotypic variables. The statistical methods useful in mendelian randomization are known as instrumental variable techniques. We present an approach to instrumental variable estimation that is useful in family data and is robust to the use of weak instruments. We illustrate our method to measure the causal influence of low-density lipoprotein on high-density lipoprotein, body mass index, triglycerides, and systolic blood pressure. We use the Framingham Heart Study data as distributed to participants in the Genetics Analysis Workshop 16.
| S-EPMC2795944 | biostudies-literature
Project description:BackgroundGrowing evidence suggests that female reproductive factors, like age at first birth (AFB), may play a potential role in the progression of lung cancer (LC). However, previous studies are susceptible to confounding factors, inadequate attention to variation by histology or reverse causality. Few studies have comprehensively evaluated their association and the causal effect remains unclear.MethodsWe aimed to determine whether AFB is causally correlated with the risk of LC, by means of utilizing aggregated data from the large genome-wide association studies conducted on AFB (251,151 individuals) and data of LC from International Lung and Cancer Consortium (ILCCO, 11,348 cases and 15,861 controls). We used 10 AFB-related single nucleotide polymorphisms as instrument variables and applied several two-sample Mendelian randomization (MR) methods. Secondary results according to different histological subtypes of lung cancer were also implemented.ResultsConventional inverse-variance weighted method indicated that genetic predisposition towards number unit (1 year) increase of AFB was associated with a 18% lower risk of LC [odds ratio (OR) =0.82, 95% confidence interval (CI): 0.69-0.97; P=0.029]. When results were examined by histotypes, an inverse association was observed between genetically predisposed number unit (1 year) increase of AFB and lung adenocarcinoma (OR =0.75, 95% CI: 0.59-0.97, P=0.017) but not with squamous cell lung cancer (OR =0.77, 95% CI: 0.57-1.05, P=0.103). The results demonstrated no association between number unit decrease of AFB and LC. Pleiotropy was not presented through sensitivity analyses including MR pleiotropy residual sum and outlier test (P=0.412). Genetic predisposition towards older AFB was additionally associated with longer years of schooling (OR =1.12, 95% CI: 1.08-1.16, P<0.001), lower body mass index (OR =0.93, 95% CI: 0.88-0.98, P=0.004) and less alcohol consumption (OR =0.99, 95% CI: 0.99-1.00, P=0.004).ConclusionsOur study suggested that older AFB was a causal protective factor in the progression of LC. Further studies elucidating the potential mechanisms are needed.
| S-EPMC8107761 | biostudies-literature
Project description:BackgroundThe objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer.MethodsPublic genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis.ResultsBased on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day.ConclusionsHabitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.
| S-EPMC7940946 | biostudies-literature
Project description:BackgroundGrowing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method.Materials and methodsWe conducted the MR study based on summary statistics from the genome-wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse-variance weighted (IVW), MR-Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis.ResultsThe results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85-0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91-1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96-1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82-1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results.ConclusionThe present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms.
| S-EPMC11224128 | biostudies-literature
Project description:Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n?=?13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p?=?0.03) and with obesity classes (Beta -6.91 •10-5; 95% CI -1.38•10-4, -5.49•10-7, p?=?0.048), but the magnitude of these effects was limited. Mendelian randomization showed no causal relation between H. pylori genetic risk score and BMI/obesity, nor between BMI or obesity genetic risk scores and H. pylori positivity. This study provides no evidence for a clinically relevant association between H. pylori and BMI/obesity.
| S-EPMC5663904 | biostudies-other