Abstract
Abstract Background: Hypertension and obesity may increase renal cell cancer (RCC) risk, but the underlying mechanism is not well understood. Given that sodium, potassium and fluid intake influence blood pressure (BP), genetic variants in the renin-angiotensin-aldosterone system (RAAS) may constitute to RCC development, as RAAS regulates BP and sodium balance. Methods: The Netherlands Cohort Study on diet and cancer with case-cohort design includes 120,852 participants aged 55-69 years. At baseline, diet and lifestyle factors were assessed using questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the iPLEX Gold system and MassARRAY software (Sequenom, Hamburg). After 20.3 years of follow-up, 13 candidate single nucleotide polymorphisms (SNPs) in seven RAAS genes known to be involved in BP regulation or sodium balance were available for Cox proportional hazards analyses for 3,583 subcohort members and 503 cases. Results: Two SNPs, AGTR1_rs1492078 (AA vs. GG) and AGTR1_rs5186 (CC vs. AA), were associated with RCC risk in the total population [hazard ratio (95% confidence interval): 0.70 (0.49-1.00) and 1.49 (1.08-2.05), respectively] and in participants with hypertension. AGT_rs3889728 (AA + AG vs. GG) showed a lower RCC risk in participants with hypertension and a higher RCC risk in participants without hypertension (P-interaction = 0.039). Associations between sodium intake and RCC risk differed among genotypes of RAAS SNPs, but tests for these and other SNP-environment interactions were not significant. Conclusion: SNPs in AGTR1 and the interplay between AGT_rs889728 and hypertension may influence RCC susceptibility. SNP-environment interactions with obesity, potassium intake and fluid intake were not significant. For sodium intake we can neither conclude nor exclude that such interactions may contribute to RCC risk. Citation Format: Ivette AG Deckers, Piet A. van den Brandt, Manon van Engeland, Roger Godschalk, Leo J. Schouten. Gene-environment interactions between SNPs in the renin-angiotensin-aldosterone system and hypertension, obesity, and blood pressure-related dietary exposures regarding renal cell cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A39.
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