Polymorphisms in genes of the renin-angiotensin-aldosterone system and renal cell cancer risk: interplay with hypertension and intakes of sodium, potassium and fluid.

摘要: Hypertension is an established risk factor for renal cell cancer (RCC). The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and closely linked to hypertension. RAAS additionally influences homeostasis of electrolytes (e.g. sodium potassium) fluid. We investigated single nucleotide polymorphisms (SNPs) in their interactions with hypertension intakes sodium, potassium fluid regarding RCC the Netherlands Cohort Study (NLCS), which was initiated 1986 included 120,852 participants aged 55 69 years. Diet lifestyle were assessed by questionnaires toenail clippings collected. Genotyping DNA performed using SEQUENOM® MassARRAY® platform a literature-based selection 13 candidate SNPs seven key genes. After 20.3 years follow-up, Cox regression analyses conducted case-cohort approach including 3,583 subcohort members 503 cases. Two AGTR1 associated risk. AGTR1_rs1492078 (AA vs. GG) decreased [hazard ratio (HR) (95% confidence interval (CI)): 0.70(0.49-1.00)], whereas AGTR1_rs5186 (CC AA) increased [HR(95%CI): 1.49(1.08-2.05)]. Associations stronger AGT_rs3889728 (AG + AA modified (p interaction = 0.039). SNP-diet not significant, although HRs suggested between ACE intake. AGT influenced susceptibility, effects Sodium intake differentially across genotypes several SNPs, yet some had probably inadequate power show significant interaction. Results suggest that may be pathway etiology.