Chao-Yuan Huang1, Shu-Pin Huang2,3,4,5, Yu-Mei Hsueh6,7, Lih-Chyang Chen8, Te-Ling Lu9, Bo-Ying Bao10,11,12. 1. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C. 2. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. 3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 4. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 5. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 6. Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C. 7. Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C. 8. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, R.O.C. 9. Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. 10. Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. bao@mail.cmu.edu.tw. 11. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. 12. Department of Nursing, Asia University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: Circadian rhythm is an internal clock that regulates the cycles of many biological functions. Epidemiological studies have linked aberrant circadian rhythm to an increased susceptibility to cancer and poor patient prognosis. However, there remains a gap in our understanding of genetic variants related to the circadian pathway in renal cell carcinoma (RCC) progression. PATIENTS AND METHODS: We examined the associations of 150 single nucleotide polymorphisms (SNPs) in 12 core circadian pathway genes with RCC risk and survival in 630 patients with RCC and controls. RESULTS: After adjusting for multiple comparisons and performing multivariate analyses, we found that the HLF rs6504958 polymorphism was significantly associated with RCC risk (q<0.05), whereas, no SNP association was significant for survival. Furthermore, the rs6504958 G allele was associated with reduced expression of HLF; consequently, a lower HLF expression was correlated with more advanced RCC. Moreover, a meta-analysis of six kidney cancer gene expression datasets demonstrated that an elevated HLF expression was associated with a favorable prognosis in patients with RCC (hazard ratio=0.70, 95% confidence interval=0.65-0.76, p<0.001). CONCLUSION: These findings implicate the potential protective role of HLF in the progression of RCC. Copyright
BACKGROUND/AIM: Circadian rhythm is an internal clock that regulates the cycles of many biological functions. Epidemiological studies have linked aberrant circadian rhythm to an increased susceptibility to cancer and poor patient prognosis. However, there remains a gap in our understanding of genetic variants related to the circadian pathway in renal cell carcinoma (RCC) progression. PATIENTS AND METHODS: We examined the associations of 150 single nucleotide polymorphisms (SNPs) in 12 core circadian pathway genes with RCC risk and survival in 630 patients with RCC and controls. RESULTS: After adjusting for multiple comparisons and performing multivariate analyses, we found that the HLF rs6504958 polymorphism was significantly associated with RCC risk (q<0.05), whereas, no SNP association was significant for survival. Furthermore, the rs6504958 G allele was associated with reduced expression of HLF; consequently, a lower HLF expression was correlated with more advanced RCC. Moreover, a meta-analysis of six kidney cancer gene expression datasets demonstrated that an elevated HLF expression was associated with a favorable prognosis in patients with RCC (hazard ratio=0.70, 95% confidence interval=0.65-0.76, p<0.001). CONCLUSION: These findings implicate the potential protective role of HLF in the progression of RCC. Copyright
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