Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study.
Adult
Colorectal cancer
Early life
Mendelian randomization
Obesity
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
04 01 2023
04 01 2023
Historique:
received:
18
07
2022
accepted:
09
12
2022
entrez:
4
1
2023
pubmed:
5
1
2023
medline:
7
1
2023
Statut:
epublish
Résumé
Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
Sections du résumé
BACKGROUND
Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.
METHODS
We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.
RESULTS
Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05).
CONCLUSIONS
Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
Identifiants
pubmed: 36600297
doi: 10.1186/s12916-022-02702-9
pii: 10.1186/s12916-022-02702-9
pmc: PMC9814460
doi:
Types de publication
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA244588
Pays : United States
Organisme : Diabetes UK
ID : 17/0005587
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA071789
Pays : United States
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA272529
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Organisme : Cancer Research UK
ID : PPRCPJT\100005
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Genet Epidemiol. 2016 May;40(4):304-14
pubmed: 27061298
Am J Epidemiol. 2018 Dec 1;187(12):2681-2685
pubmed: 30188969
PLoS One. 2015 Apr 21;10(4):e0120758
pubmed: 25898129
JAMA. 2010 Jan 20;303(3):242-9
pubmed: 20071470
Int J Epidemiol. 2019 Jun 1;48(3):713-727
pubmed: 30535378
Int J Epidemiol. 2016 Aug;45(4):1103-1112
pubmed: 27466312
Nat Genet. 2019 Jan;51(1):76-87
pubmed: 30510241
J Clin Oncol. 2010 Sep 10;28(26):4052-7
pubmed: 20644083
Cancer Epidemiol Biomarkers Prev. 2015 Apr;24(4):690-7
pubmed: 25777804
Stat Med. 2017 May 20;36(11):1783-1802
pubmed: 28114746
Gut. 2016 Aug;65(8):1289-95
pubmed: 25986947
Pediatrics. 2005 Aug;116(2):473-80
pubmed: 16061606
Hum Mol Genet. 2021 Feb 25;29(24):3966-3973
pubmed: 33276378
Gut. 2021 Jul;70(7):1325-1334
pubmed: 33632709
Int J Epidemiol. 2003 Feb;32(1):1-22
pubmed: 12689998
BMJ. 2021 Oct 26;375:n2233
pubmed: 34702754
J Natl Cancer Inst. 2022 Sep 9;114(9):1296-1300
pubmed: 35438160
BMJ. 2020 May 06;369:m1203
pubmed: 32376654
Int J Epidemiol. 2013 Oct;42(5):1497-501
pubmed: 24159078
Int J Epidemiol. 2021 Nov 10;50(5):1580-1592
pubmed: 33783488
JAMA. 2021 Oct 26;326(16):1614-1621
pubmed: 34698778
N Engl J Med. 2017 Jul 6;377(1):13-27
pubmed: 28604169
Am J Clin Nutr. 2010 May;91(5):1499S-1505S
pubmed: 20335542
Am J Epidemiol. 2015 Feb 15;181(4):251-60
pubmed: 25632051
Genet Epidemiol. 2016 Nov;40(7):597-608
pubmed: 27625185
Int J Epidemiol. 2011 Jun;40(3):755-64
pubmed: 21414999
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Curr Epidemiol Rep. 2018;5(3):214-220
pubmed: 30148040
Cancer. 2017 Oct 15;123(20):4022-4030
pubmed: 28736986
Stat Med. 2008 Apr 15;27(8):1133-63
pubmed: 17886233
N Engl J Med. 2007 Dec 6;357(23):2371-9
pubmed: 18057339
Int J Epidemiol. 2017 Dec 1;46(6):1734-1739
pubmed: 28398548
PLoS Genet. 2022 Jul 18;18(7):e1010290
pubmed: 35849575
Stat Med. 2017 Dec 20;36(29):4705-4718
pubmed: 28960498
Int J Cancer. 2021 Oct 1;149(7):1421-1425
pubmed: 34004046
Int J Cancer. 2018 Feb 15;142(4):729-740
pubmed: 29023686
Rev Panam Salud Publica. 2019 Jan 04;43:e3
pubmed: 31093227
BMC Med. 2020 Dec 17;18(1):396
pubmed: 33327948