RGD Reference Report - Gene polymorphism of cytochrome P450 significantly affects lung cancer susceptibility. - Rat Genome Database

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Gene polymorphism of cytochrome P450 significantly affects lung cancer susceptibility.

Authors: Li, Meng  Li, Anqi  He, Ruiqing  Dang, Wenhui  Liu, Xinyu  Yang, Tian  Shi, Puyu  Bu, Xiang  Gao, Dan  Zhang, Ning  Du, Shuli  Jin, Tianbo  Chen, Mingwei 
Citation: Li M, etal., Cancer Med. 2019 Aug;8(10):4892-4905. doi: 10.1002/cam4.2367. Epub 2019 Jul 1.
RGD ID: 151665340
Pubmed: PMID:31264381   (View Abstract at PubMed)
PMCID: PMC6712450   (View Article at PubMed Central)
DOI: DOI:10.1002/cam4.2367   (Journal Full-text)


BACKGROUND: Cytochrome P450 (CYPs) are heme proteins involved in the metabolism of a variety of endogenous and exogenous substances and play an important role in the carcinogenesis mechanisms of environmental and hereditary factors. The objective of this study was to investigate how polymorphisms of CYPs correlate with lung cancer (LC) susceptibility.
METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped in this study. The chi-square test and unconditional logistic regression model were used to evaluate the correlation between SNPs and LC susceptibility. The expressions and survival data of genes in patients with LC were mined using Oncomine and Kaplan-Meier Plotter database.
RESULTS: Four SNPs were found to be significantly associated with the risk of LC development (P < 0.05). The most significant correlation was that the A allele and AA genotype of CYP2D6 rs1065852 were associated with increased risk of LC development (adjusted odds ratio [OR] = 1.35, 95% confidence interval [95%CI] = 1.13-1.60, P = 9.04e-4; OR = 1.83, 95%CI = 1.29-2.59, P = 0.001 respectively). Similar association of this variant was also found in the subgroups of male patients, cases in III-IV stages, positive lymph node, squamous cell carcinomas and adenocarcinomas. Whereas rs1065852 was considered as protective factor in females (adjusted OR = 0.33, 95% CI = 0.16-0.70, P = 0.004). In stratified analyses, the association of CYP24A1 rs2762934, CYP24A1 rs6068816, CYP20A1 rs2043449 polymorphism with LC risk appeared stronger in some subgroups. CYP2D6, CYP24A1 and CYP20A1 are overexpressed in some pathological types of LC (P < 0.05), and high levels of CYP2D6 and CYP20A1 indicate poor and good prognosis of LC, respectively.
CONCLUSION: This study revealed that rs1065852, rs2043449, rs2762s934, and rs6068816 of CYPs were associated with LC susceptibility in the Northwestern Chinese Han population; CYP2D6 and CYP20A1 were overexpressed and correlated with prognosis of LC.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP24A1Humanlung cancer sexual_dimorphism IAGP DNA:SNP:intron: (rs2765934) (human)RGD 
Cyp24a1Ratlung cancer sexual_dimorphism ISOCYP24A1 (Homo sapiens)DNA:SNP:intron: (rs2765934) (human)RGD 
Cyp24a1Mouselung cancer sexual_dimorphism ISOCYP24A1 (Homo sapiens)DNA:SNP:intron: (rs2765934) (human)RGD 
CYP24A1Humanlung small cell carcinoma susceptibilityIAGP DNA:SNP:CDS: (rs6068816) (human)RGD 
Cyp24a1Ratlung small cell carcinoma susceptibilityISOCYP24A1 (Homo sapiens)DNA:SNP:CDS: (rs6068816) (human)RGD 
Cyp24a1Mouselung small cell carcinoma susceptibilityISOCYP24A1 (Homo sapiens)DNA:SNP:CDS: (rs6068816) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP24A1HumanNeoplasm of the lung sexual_dimorphism IAGP DNA:SNP:intron: (rs2765934) RGD 
CYP24A1HumanSmall cell lung carcinoma susceptibilityIAGP DNA:SNP:CDS: (rs6068816) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cyp24a1  (cytochrome P450, family 24, subfamily a, polypeptide 1)

Genes (Mus musculus)
Cyp24a1  (cytochrome P450, family 24, subfamily a, polypeptide 1)

Genes (Homo sapiens)
CYP24A1  (cytochrome P450 family 24 subfamily A member 1)


Additional Information