RGD Reference Report - Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. - Rat Genome Database

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Folate metabolism genes, vegetable intake and renal cancer risk in central Europe.

Authors: Moore, LE  Hung, R  Karami, S  Boffetta, P  Berndt, S  Hsu, CC  Zaridze, D  Janout, V  Kollarova, H  Bencko, V  Navratilova, M  Szeszenia-Dabrowska, N  Mates, D  Mukeria, A  Holcatova, I  Yeager, M  Chanock, S  Garcia-Closas, M  Rothman, N  Chow, WH  Brennan, P 
Citation: Moore LE, etal., Int J Cancer. 2008 Apr 15;122(8):1710-5.
RGD ID: 6893654
Pubmed: PMID:18098291   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.23318   (Journal Full-text)

In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53-0.83; p-trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 -391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8-62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2-405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8+227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls genotyped in this study. Having at least 1 variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17-1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p-trend = 0.001), but not among those in the highest tertile (p-interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 -405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.57-0.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p-interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma susceptibilityIAGP 6893654DNA:missense mutation:cds:p.A222V (rs1801133) (human)RGD 
renal cell carcinoma susceptibilityISOMTHFR (Homo sapiens)6893654; 6893654DNA:missense mutation:cds:p.A222V (rs1801133) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal renal morphology susceptibilityIAGP 6893654DNA:missense mutation:cds:p.A222V (rs1801133)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Mus musculus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Homo sapiens)
MTHFR  (methylenetetrahydrofolate reductase)


Additional Information