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Folate metabolism genes, vegetable intake and renal cancer risk in central Europe
Author(s) -
Moore Lee E.,
Hung Rayjean,
Karami Sara,
Boffetta Paolo,
Berndt Sonya,
Hsu Charles C.,
Zaridze David,
Janout Vladimir,
Kollarova Helen,
Bencko Vladmir,
Navratilova Marie,
SzeszeniaDabrowska N.,
Mates Dana,
Mukeria Anush,
Holcatova Ivana,
Yeager Meredith,
Chanock Stephen,
GarciaClosas Montse,
Rothman Nat,
Chow WongHo,
Brennan Paul
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23318
Subject(s) - mtrr , methylenetetrahydrofolate reductase , odds ratio , medicine , confidence interval , single nucleotide polymorphism , renal cell carcinoma , genotype , allele , case control study , gastroenterology , oncology , endocrinology , genetics , biology , gene
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. © 2007 Wiley‐Liss, Inc.