Yi Can, Huang Chao, Wang Huan, Wang Chen, Dong Lijuan, Gu Xiuli, Feng Xianhong, Chen Bifeng
Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.
Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China; Department of Reproductive Genetics, Wuhan Tongji Reproductive Medicine Hospital, Wuhan, China.
Pathol Res Pract. 2020 Jan;216(1):152735. doi: 10.1016/j.prp.2019.152735. Epub 2019 Nov 11.
CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.
CYP24A1是维生素D调节中的一个关键基因，据报道在增强免疫活性和抑制肿瘤发生中起重要作用。先前的研究表明，CYP24A1基因中的rs2585428、rs4809960、rs6022999和rs6068816可能与癌症风险密切相关。为了验证这些发现，我们在此调查了中国中部人群（426例结肠癌患者、361例直肠癌患者和800例健康对照）中这四种多态性与结直肠癌（CRC）风险的关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型，并通过测序进行确认。我们的结果显示，rs4809960和rs6022999与CRC风险密切相关，尤其是与结肠癌风险相关。此外，由rs2585428（G>A）、rs4809960（T>C）、rs6022999（A>G）和rs6068816（C>T）组成的单倍型分析表明，单倍型ATGC显著降低了CRC风险，尤其是结肠癌风险。单倍型GCAT显著增加了CRC风险，尤其是直肠癌风险。然而，仅发现单倍型ACAC与CRC风险增加有关。为了提高统计效力，进一步进行了更新的荟萃分析。结果显示，rs2585428与白种人群的癌症风险相关，rs4809960与白种人群的乳腺癌风险相关，rs6022999与亚洲人群的癌症风险相关。总体而言，rs4809960和rs6022999可能是预测中国人群结肠癌风险的遗传生物标志物，rs2585428和rs6022999可能分别与白种人群和亚洲人群的癌症易感性相关。
