RGD Reference Report - CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility. - Rat Genome Database

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CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility.

Authors: Hirata, H  Hinoda, Y  Okayama, N  Suehiro, Y  Kawamoto, K  Kikuno, N  Rabban, JT  Chen, LM  Dahiya, R 
Citation: Hirata H, etal., Cancer. 2008 May 1;112(9):1964-73.
RGD ID: 2301040
Pubmed: PMID:18318428   (View Abstract at PubMed)
DOI: DOI:10.1002/cncr.23392   (Journal Full-text)

BACKGROUND: In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and activation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer. METHODS: DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1. RESULTS: A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35-8.93). CONCLUSIONS: This is the first report on the combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer that suggests a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial cancer  IAGP 2301040DNA:SNP:CDS:rs4646903 T/T genotype more ...RGD 
endometrial cancer  ISOCYP1A1 (Homo sapiens)2301040; 2301040 RGD 
endometrial cancer  IAGP 2301040DNA:SNP:haplotype:rs3736599 (GA+AA) combined with SULT1A1 SNP rs9282861 (GA + AA) or with CYP1A1 SNP rs4646903 (TT)RGD 
endometrial cancer  ISOSULT1E1 (Homo sapiens)2301040; 2301040 RGD 
Endometrial Neoplasms  IAGP 2301040DNA:SNP:CDS more ...RGD 
Endometrial Neoplasms  ISOSULT1A1 (Homo sapiens)2301040; 2301040 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)
Sult1a1  (sulfotransferase family 1A member 1)
Sult1e1  (sulfotransferase family 1E member 1)

Genes (Mus musculus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)
Sult1a1  (sulfotransferase family 1A, phenol-preferring, member 1)
Sult1e1  (sulfotransferase family 1E, member 1)

Genes (Homo sapiens)
CYP1A1  (cytochrome P450 family 1 subfamily A member 1)
SULT1A1  (sulfotransferase family 1A member 1)
SULT1E1  (sulfotransferase family 1E member 1)


Additional Information