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Browsing by Author "Li, Chunying"
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Item Genetic variants in ELOVL2 and HSD17B12 predict melanoma‐specific survival(Wiley, 2019) Dai, Wei; Liu, Hongliang; Xu, Xinyuan; Jie, Ge; Luo, Sheng; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Li, Xin; Nan, Hongmei; Li, Chunying; Wei, Qingyi; Epidemiology, School of Public HealthFatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single‐nucleotide polymorphisms (SNPs) in 149 genes of the fatty‐acid synthesis pathway with cutaneous melanoma disease‐specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome‐wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses’ Health and Health Professionals Follow‐up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51–0.84 and p = 8.34 × 10−4) and 2.29 (1.55–3.39 and p = 3.61 × 10−5), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies.Item Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival(Wiley, 2020-03-31) Dai, Wei; Liu, Hongliang; Chen, Ka; Xu, Xinyuan; Qian, Danwen; Luo, Sheng; Amos, Christopher I.; Lee, Jeffrey E.; Li, Xin; Nan, Hongmei; Li, Chunying; Wei, Qingyi; Epidemiology, School of Public HealthA few single-nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival though genome-wide association studies, but stringent multiple testing corrections required for the hypothesis-free testing may have masked some true associations. Using a hypothesis-driven analysis approach, we sought to evaluate associations between SNPs in ketone body metabolic pathway genes and CM survival. We comprehensively assessed associations between 4,196 (538 genotyped and 3,658 imputed) common SNPs in ketone body metabolic pathway genes and CM survival, using a dataset of 858 patients of a case-control study from The University of Texas M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients from the Nurses’ Health Study and the Health Professionals Follow-up Study as the replication set. There were 95/858 (11.1%) and 48/409 (11.5%) patients who died of CM, respectively. We identified two independent SNPs (i.e., PDSS1 rs12254548 G>C and SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards ratios of 0.58 (95% confidence interval [CI]=0.44-0.76, P=9.00×10−5) and 1.98 (95% CI=1.34-2.94, P=6.30×10−4), respectively. Additionally, associations between genotypes of the SNPs and mRNA expression levels of their corresponding genes support the biologic plausibility of a role for these two variants in CM tumor progression and survival. Once validated by larger studies, PDSS1 rs12254548 and SLC16A6 rs71387392 may be biomarker for CM survival.Item Genetic Variants in WNT2B and BTRC Predict Melanoma Survival(Elsevier, 2017) Shu, Qiong; Liu, Hongliang; Han, Peng; Li, Chunying; Wang, Yanru; Wu, Wenting; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Han, Jiali; Wei, Qingyi; Department of Epidemiology, Richard M. Fairbanks School of Public HealthCutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an impact on development, invasion and metastasis of CM, thus likely affecting CM prognosis. Using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the associations of 19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal genes with CM-specific survival (CMSS) and then validated significant SNPs in another GWAS from Harvard University. In the single-locus analysis, 1,855 SNPs were significantly associated with CMSS at P < 0.05, of which 547 SNPs were still considered noteworthy after the correction by the false positive report probability. In the replication, two SNPs remained significantly associated with CMSS after multiple comparison correction. By performing functional prediction and stepwise selection, we identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997 G>A) that showed a predictive role in CMSS, with an effect-allele-attributed hazards ratio [adjHR of 1.99 (95% confidence interval (CI) = 1.41-2.81, P = 8.10E-05) and 0.61 (0.46-0.80, 3.12E-04), respectively]. Collectively, these variants in the Wnt pathway genes may be biomarkers for outcomes of CM patients, if validated by larger studies.