Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk.
Gene
; 927: 148732, 2024 Nov 15.
Article
de En
| MEDLINE
| ID: mdl-38945312
ABSTRACT
BACKGROUND:
Soy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer.METHODS:
A two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk.RESULTS:
A nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model adjusted OR = 0.69, 95 %CI = 0.57-0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008).CONCLUSIONS:
We identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Glycine max
/
Glucuronosyltransferase
/
Prédisposition génétique à une maladie
/
Polymorphisme de nucléotide simple
/
Isoflavones
/
Tumeurs du poumon
Limites:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Langue:
En
Journal:
Gene
Année:
2024
Type de document:
Article
Pays de publication:
Pays-Bas