Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five‐center case‐control study

Abstract

Background Wilms tumor is the most frequent renal malignancy in children. YTHDF1 is associated with the development of several kinds of cancers, yet whether common variants of the YTHDF1 gene influence Wilms tumor risk is unknown. We present, here, a hospital‐based case‐control study specifically designed to investigate the role of YTHDF1 genetic variants on Wilms tumor. Methods We successfully genotyped samples of 408 Wilms tumor cases and 1198 controls which were collected from five hospitals across China. The unconditional logistic regression was adopted to analyze the contributions of YTHDF1 gene single nucleotide polymorphisms (SNPs) to the risk of Wilms tumor. The odds ratio (OR) and 95% confidence interval (CI) were generated to evaluate the conferring risk of YTHDF1 gene SNPs (rs6011668 C>T, rs6090311 A>G). Results Neither of the two SNPs could contribute to the risk of Wilms tumor. A negative association was also detected in the combined effects of protective genotypes on Wilms tumor risk. The stratification analysis revealed that compared with those with CC genotype, rs6011668 CT/TT genotype was associated with increased Wilms tumor risk in those ≤18 months (OR = 1.54, 95% CI = 1.02–2.30, p = 0.038), and with decreased Wilms tumor risk in those >18 months (OR = 0.70, 95% CI = 0.50–0.97, p = 0.034). Conclusion Our present work sheds some light on the potential role of YTHDF1 gene polymorphisms on Wilms tumor risk.

Association of N6-methyladenosine readers' genes variation and expression level with pulmonary tuberculosis

“…Liu et al . found that compared with the CC genotype, YTHDF1 rs6011668 CT/TT genotype was associated with an increased risk of Wilms tumor in patients ≤18 months in stratification analysis, although this SNP might not contribute to the risk of Wilms tumor ( 26 ). The results by Zeng et al .…”

“…The final consequences of m6A modification on mRNA fate were executed by “reader” proteins, and these readers' genes mainly included the YTH family (YTHDC1-2 and YTHDF1-3). The contribution of m6A readers' genes to cancer was widely studied, and multiple SNPs located in m6A readers' genes had been found to affect the risk of cancer ( 23 , 26 , 27 ). Liu et al .…”

The potential role of m6A reader YTHDF1 as diagnostic biomarker and the signaling pathways in tumorigenesis and metastasis in pan-cancer

“…Single nucleotide polymorphisms in the YTHDF1 gene(rs6011668 C to T and rs6090311 A to G) also contributed to occurrence of neuroblastoma [ 67 ]. Additionally, YTHDF1 gene polymorphisms(rs6011668 C > T, rs6090311 A > G) affected Wilms tumor susceptibility [ 68 ]. The other two YTHDF1 SNPs (rs6011668 C > T and rs6090311 A > G) was to be investigated in 313 patients with HCC and 1446 controls.…”

Overexpression of YTHDC2 contributes to the progression of prostate cancer and predicts poor outcomes in patients with prostate cancer

“…To date, several m6A binding proteins have been identified, such as the YTH (YT521-B homology) domain protein family, namely YTHDF1, [11] YTHDF2, [12] YTHDF3, [13] YTHDC1, [14] and YTHDC2 [15] and the nuclear heterogeneous protein HNRNP family, namely HNRNPA2B1 and HNRNPC. [15] YTH domain-containing 2 (YTHDC2) is the largest N6-methyladenosine (m6A) binding protein of the YTH protein family and the only member containing ATPdependent RNA helicase activity, and its biological function has not yet been fully elucidated.…”

“…In recent years, as the most abundant mRNA modification in eukaryotic cells, [ 9,10 ] m6A RNA modifications are widely regarded as essential epigenetic modifications in many biological processes through the dynamic regulation of gene expression and have received widespread attention. It is well known that m6A modifications are essential for a variety of pathological processes, including cancer development and progression.2‐6 The current research found that m6A is a dynamic process, and its function is determined by the “Writer,” “Eraser,” and “Reader.” The function of m6A is recognized through the m6A binding protein, which is the “reader.” To date, several m6A binding proteins have been identified, such as the YTH (YT521‐B homology) domain protein family, namely YTHDF1, [ 11 ] YTHDF2, [ 12 ] YTHDF3, [ 13 ] YTHDC1, [ 14 ] and YTHDC2 [ 15 ] and the nuclear heterogeneous protein HNRNP family, namely HNRNPA2B1 and HNRNPC. [ 15 ] YTH domain‐containing 2 (YTHDC2) is the largest N6‐methyladenosine (m6A) binding protein of the YTH protein family and the only member containing ATP‐dependent RNA helicase activity, and its biological function has not yet been fully elucidated.…”