Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
08
10
2021
revised:
28
01
2022
accepted:
16
06
2022
pubmed:
29
7
2022
medline:
9
9
2022
entrez:
28
7
2022
Statut:
ppublish
Résumé
Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses. The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined. In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer. Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
Sections du résumé
BACKGROUND
Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.
METHODS
The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.
RESULTS
In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.
CONCLUSIONS
Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer.
IMPACT
The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
Identifiants
pubmed: 35900194
pii: 707316
doi: 10.1158/1055-9965.EPI-21-1176
pmc: PMC9437565
mid: EMS146283
doi:
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1839-1848Subventions
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C864/A14136
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A29019
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M012190/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8221/A29017
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A14136
Pays : United Kingdom
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
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