The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study
Abstract Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumpt...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-53926-z |
| _version_ | 1797275099396571136 |
|---|---|
| author | Jie Yang Xiang Qu An-jie Zheng Fan Jiang Hui Chang Jin-ru zhang Li-juan Yan Peng Ning |
| author_facet | Jie Yang Xiang Qu An-jie Zheng Fan Jiang Hui Chang Jin-ru zhang Li-juan Yan Peng Ning |
| author_sort | Jie Yang |
| collection | DOAJ |
| description | Abstract Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41–0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38–0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40–4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1. |
| first_indexed | 2024-03-07T15:09:31Z |
| format | Article |
| id | doaj.art-cd8cdb8e2e65482a84055e852899fd40 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:09:31Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cd8cdb8e2e65482a84055e852899fd402024-03-05T18:45:39ZengNature PortfolioScientific Reports2045-23222024-02-0114111010.1038/s41598-024-53926-zThe causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization studyJie Yang0Xiang Qu1An-jie Zheng2Fan Jiang3Hui Chang4Jin-ru zhang5Li-juan Yan6Peng Ning7Department of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalDepartment of Oncology, Baoji Gaoxin HospitalAbstract Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41–0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38–0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40–4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.https://doi.org/10.1038/s41598-024-53926-zAlcohol consumptionMendelian randomizationEndometrial cancerCausal inferenceProtective factors |
| spellingShingle | Jie Yang Xiang Qu An-jie Zheng Fan Jiang Hui Chang Jin-ru zhang Li-juan Yan Peng Ning The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study Scientific Reports Alcohol consumption Mendelian randomization Endometrial cancer Causal inference Protective factors |
| title | The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study |
| title_full | The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study |
| title_fullStr | The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study |
| title_full_unstemmed | The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study |
| title_short | The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study |
| title_sort | causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a mendelian randomization study |
| topic | Alcohol consumption Mendelian randomization Endometrial cancer Causal inference Protective factors |
| url | https://doi.org/10.1038/s41598-024-53926-z |
| work_keys_str_mv | AT jieyang thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT xiangqu thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT anjiezheng thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT fanjiang thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT huichang thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT jinruzhang thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT lijuanyan thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT pengning thecausaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT jieyang causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT xiangqu causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT anjiezheng causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT fanjiang causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT huichang causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT jinruzhang causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT lijuanyan causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy AT pengning causaleffectsofgeneticallypredictedalcoholconsumptiononendometrialcancerriskfromamendelianrandomizationstudy |