Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.
JAMA Netw Open
; 7(5): e2413708, 2024 May 01.
Article
en En
| MEDLINE
| ID: mdl-38809553
ABSTRACT
Importance Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective:
To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, andParticipants:
This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures H pylori treatment and nutrition supplementation. Main Outcomes andMeasures:
Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk.Results:
Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100â¯228 participants (mean [SD] age, 53.69 [11.00] years; 57â¯357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Helicobacter pylori
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Infecciones por Helicobacter
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Predisposición Genética a la Enfermedad
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
JAMA Netw Open
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos