Variants in blood pressure genes and the risk of renal cell carcinoma

Gabriella Andreotti, Paolo Boffetta, Philip S. Rosenberg, Sonja I. Berndt, Sara Karami, Idan Menashe, Meredith Yeager, Stephen J. Chanock, David Zaridze, Vsevolod Matteev, Vladimir Janout, Hellena Kollarova, Vladimir Bencko, Marie Navratilova, Neonilia Szeszenia-Dabrowska, Dana Mates, Nathaniel Rothman, Paul Brennan, Wong Ho Chow, Lee E. Moore

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Hypertension is a known risk factor for renal cell carcinoma (RCC), although the underlying biological mechanisms of its action are unknown. To clarify the role of hypertension in RCC, we examined the risk of RCC in relation to 142 single-nucleotide polymorphisms (SNPs) in eight genes having a role in blood pressure control.We analyzed 777 incident and histologically confirmed RCC cases and 1035 controls who completed an in-person interview as part of a multi-center, hospital-based case-control study in Central Europe. Genotyping was conducted with an Illumina® GoldenGate® Oligo Pool All assay using germ line DNA. Of the eight genes examined, AGT (angiotensinogen) was most strongly associated with RCC (minimum P-value permutation test 5 0.02). Of the 17 AGT tagging SNPs considered, associations were strongest for rs1326889 [odds ratio (OR) 5 1.35, 95% confidence interval (CI) 5 1.15-1.58] and rs2493137 (OR 5 1.31, 95% CI 5 1.12-1.54), which are located in the promoter. Stratified analysis revealed that the effects of the AGT SNPs were statistically significant in participants with hypertension or high body mass index (BMI) (≥25 kg/m2), but not in subjects without hypertension and with a normal BMI (<25 kg/m2). Also, haplotypes with riskconferring alleles of markers located in the promoter and intron 1 regions of AGT were significantly associated with RCC compared with the common haplotype in subjects with hypertension or high BMI (global P 5 0.003). Our findings suggest that common genetic variants of AGT, particularly those in the promoter, increase RCC risk among subjects who are hypertensive or overweight. Published by Oxford University Press 2010.

Original languageEnglish
Pages (from-to)614-620
Number of pages7
JournalCarcinogenesis
Volume31
Issue number4
DOIs
StatePublished - 4 Jan 2010
Externally publishedYes

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