Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response.
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:
06 03 2023
06 03 2023
Historique:
received:
06
07
2022
revised:
19
09
2022
accepted:
19
12
2022
pubmed:
29
12
2022
medline:
8
3
2023
entrez:
28
12
2022
Statut:
ppublish
Résumé
Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. These findings can guide potential prevention treatments.
Sections du résumé
BACKGROUND
Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.
METHODS
A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.
RESULTS
Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).
CONCLUSIONS
Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.
IMPACT
These findings can guide potential prevention treatments.
Identifiants
pubmed: 36576985
pii: 712418
doi: 10.1158/1055-9965.EPI-22-0763
pmc: PMC9992283
mid: NIHMS1861189
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
315-328Subventions
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 : K05 CA154337
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164930
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
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Pays : United States
Organisme : NHLBI NIH HHS
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Organisme : NHLBI NIH HHS
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Organisme : NCI NIH HHS
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Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA048998
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA137088
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100003C
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 CP010200
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Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008C
Pays : United States
Organisme : NCI NIH HHS
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Pays : United States
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Pays : United States
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ID : U01 CA086308
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Pays : United States
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Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES013678
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136726
Pays : United States
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UM1 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : K05 CA152715
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA122839
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Organisme : NHLBI NIH HHS
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Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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