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Folate metabolism genes, vegetable intake and renal cancer risk in central Europe.
Int J Cancer 2008; 122(8):1710-5IJ

Abstract

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.

Authors+Show Affiliations

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. moorele@mail.nih.gov

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

18098291

Citation

Moore, Lee E., et al. "Folate Metabolism Genes, Vegetable Intake and Renal Cancer Risk in Central Europe." International Journal of Cancer, vol. 122, no. 8, 2008, pp. 1710-5.
Moore LE, Hung R, Karami S, et al. Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer. 2008;122(8):1710-5.
Moore, L. E., Hung, R., Karami, S., Boffetta, P., Berndt, S., Hsu, C. C., ... Brennan, P. (2008). Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. International Journal of Cancer, 122(8), pp. 1710-5.
Moore LE, et al. Folate Metabolism Genes, Vegetable Intake and Renal Cancer Risk in Central Europe. Int J Cancer. 2008 Apr 15;122(8):1710-5. PubMed PMID: 18098291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. AU - Moore,Lee E, AU - Hung,Rayjean, AU - Karami,Sara, AU - Boffetta,Paolo, AU - Berndt,Sonya, AU - Hsu,Charles C, AU - Zaridze,David, AU - Janout,Vladimir, AU - Kollarova,Helen, AU - Bencko,Vladmir, AU - Navratilova,Marie, AU - Szeszenia-Dabrowska,N, AU - Mates,Dana, AU - Mukeria,Anush, AU - Holcatova,Ivana, AU - Yeager,Meredith, AU - Chanock,Stephen, AU - Garcia-Closas,Montse, AU - Rothman,Nat, AU - Chow,Wong-Ho, AU - Brennan,Paul, PY - 2007/12/22/pubmed PY - 2008/3/7/medline PY - 2007/12/22/entrez SP - 1710 EP - 5 JF - International journal of cancer JO - Int. J. Cancer VL - 122 IS - 8 N2 - 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. SN - 1097-0215 UR - https://www.unboundmedicine.com/medline/citation/18098291/Folate_metabolism_genes_vegetable_intake_and_renal_cancer_risk_in_central_Europe_ L2 - https://doi.org/10.1002/ijc.23318 DB - PRIME DP - Unbound Medicine ER -