A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
25
11
2022
revised:
25
02
2023
accepted:
24
05
2023
medline:
3
8
2023
pubmed:
30
5
2023
entrez:
30
5
2023
Statut:
ppublish
Résumé
Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
Identifiants
pubmed: 37249599
pii: 727007
doi: 10.1158/0008-5472.CAN-22-3713
pmc: PMC10391330
doi:
Substances chimiques
GREM1 protein, human
0
Intercellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2572-2583Subventions
Organisme : NIH HHS
ID : S10 OD028685
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008I
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201700006I
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201407
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164930
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA059045
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA137088
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG018033
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA086308
Pays : United States
Organisme : NIA NIH HHS
ID : HHSN271201100004C
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100004C
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100003C
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100002C
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100046C
Pays : United States
Organisme : NCI NIH HHS
ID : K05 CA154337
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR000421
Pays : United States
Organisme : NCI NIH HHS
ID : K05 CA152715
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA153323
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA097325
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004446
Pays : United States
Organisme : NCI NIH HHS
ID : Z01 CP010200
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA074783
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034987
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA066635
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197350
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA081488
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA063464
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA033619
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA054281
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136726
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA072520
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA042182
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197735
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA151993
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA137178
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197735
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA151993
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA137178
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA055075
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA084968
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA048998
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES013678
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201407
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA196569
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197350
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA081488
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148107
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Organisme : NCI NIH HHS
ID : R01 CA076366
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA074794
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA074794
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008I
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148107
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA081488
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148107
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA114347
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA122839
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
Références
PLoS Genet. 2007 Jul;3(7):e115
pubmed: 17658951
Science. 2007 May 11;316(5826):889-94
pubmed: 17434869
Cell Mol Gastroenterol Hepatol. 2021;12(1):181-197
pubmed: 33601062
Cancer Res. 2012 Apr 15;72(8):2036-44
pubmed: 22367214
Nat Commun. 2021 Jul 28;12(1):4579
pubmed: 34321471
Exp Cell Res. 2006 Apr 15;312(7):1119-26
pubmed: 16480715
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
PLoS One. 2016 Jul 05;11(7):e0157521
pubmed: 27379672
Nature. 1990 Aug 30;346(6287):850-3
pubmed: 2392150
Lancet. 2014 Aug 30;384(9945):727-8
pubmed: 25129326
Mol Aspects Med. 2019 Oct;69:2-9
pubmed: 31233770
PLoS One. 2007 Dec 26;2(12):e1361
pubmed: 18159244
Gastroenterology. 2013 Apr;144(4):799-807.e24
pubmed: 23266556
Bone. 2020 Aug;137:115455
pubmed: 32473315
Int J Mol Sci. 2020 Sep 29;21(19):
pubmed: 33003475
Nat Genet. 2023 Jan;55(1):89-99
pubmed: 36539618
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Genet Epidemiol. 2013 Sep;37(6):603-13
pubmed: 23873611
Gut. 2015 Oct;64(10):1623-36
pubmed: 26187503
Nat Med. 2015 Jan;21(1):62-70
pubmed: 25419707
Nat Commun. 2019 May 14;10(1):2154
pubmed: 31089142
Am J Epidemiol. 2017 Oct 1;186(7):762-770
pubmed: 28978192
Carcinogenesis. 2016 Jun;37(6):547-556
pubmed: 27207650
Gastroenterology. 2021 Jul;161(1):239-254.e9
pubmed: 33819486
Dev Cell. 2012 Jan 17;22(1):183-96
pubmed: 22227309
Am J Med Genet A. 2019 Feb;179(2):266-279
pubmed: 30569497
Am J Epidemiol. 2013 Jul 1;178(1):144-52
pubmed: 23821317
CA Cancer J Clin. 2018 Jan;68(1):31-54
pubmed: 29160902
J Med Genet. 2015 May;52(5):317-21
pubmed: 25676610
Front Endocrinol (Lausanne). 2020 Apr 09;11:165
pubmed: 32328030
Lancet. 2016 Apr 2;387(10026):1377-1396
pubmed: 27115820
Am J Epidemiol. 2019 Apr 1;188(4):760-767
pubmed: 30649161
Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1824-33
pubmed: 24994789
J Natl Cancer Inst. 2021 Jan 4;113(1):38-47
pubmed: 32324875
Lancet. 2016 Aug 20;388(10046):776-86
pubmed: 27423262
BMJ. 2019 Jul 3;366:l4067
pubmed: 31270083
Nat Genet. 2019 Jan;51(1):76-87
pubmed: 30510241
Nat Genet. 2008 May;40(5):623-30
pubmed: 18372905
Science. 2002 Jul 26;297(5581):612-5
pubmed: 12052901
Oncotarget. 2019 Jul 23;10(45):4630-4639
pubmed: 31384391
Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):70-81
pubmed: 21071539
Mol Cell. 2004 Feb 27;13(4):511-22
pubmed: 14992721
Stem Cell Res Ther. 2018 May 2;9(1):125
pubmed: 29720241
Mol Biol Cell. 2005 Jan;16(1):1-13
pubmed: 15509653
J Natl Cancer Inst. 2019 Feb 1;111(2):146-157
pubmed: 29917119
Expert Rev Gastroenterol Hepatol. 2015;9(11):1339-42
pubmed: 26366838
Cells. 2021 Sep 27;10(10):
pubmed: 34685534
Hum Mol Genet. 2019 Jan 1;28(1):166-174
pubmed: 30239722
Nat Genet. 2009 Jan;41(1):18-24
pubmed: 19079260
Sci Rep. 2015 May 20;5:10442
pubmed: 25990418
Dev Cell. 2013 Sep 30;26(6):629-44
pubmed: 24091014