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  1. Choong EKM, Shu X, Leung KCM, Lo ECM
    J Dent, 2022 Dec;127:104351.
    PMID: 36280004 DOI: 10.1016/j.jdent.2022.104351
    OBJECTIVES: To summarise evidence on the change in oral health-related quality of life (OHRQoL) before and after rehabilitation with removable partial dentures (RPDs) amongst partially edentulous adults.

    DATA: Studies assessing OHRQoL amongst patients aged ≥18 years, before and after rehabilitation with RPDs of any type and design, were included. The quality of included studies was evaluated using the Cochrane risk of bias tools. Meta-analysis was conducted using a random-effect model.

    SOURCES: MEDLINE, EMBASE and CENTRAL, up to March 29, 2022.

    STUDY SELECTION AND RESULTS: Thirteen studies were eligible and eight were included in the meta-analysis. The studies had moderate to serious risk of bias. There was a very low level of certainty that OHRQoL, as measured using OHIP-14, improved 3 months after RPDs were fitted (222 participants, MD: -12.0, 95% CI: -16.1, -7.9, p<0.001) and after 6 months (101 participants, MD: -10.5, 95% CI: -16.4, -4.6, p<0.001). At 12 months post-treatment, RPD rehabilitation did not result in statistically significant improvement in OHIP-14 scores (62 participants, MD: -12.7, 95% CI: -26.1, 0.6, p = 0.06). However, the assessment using OHIP-49 at 12 months showed significant improvement (87 participants, MD: -34.8, 95% CI: -41.9, -27.7, p<0.001), with low certainty of evidence.

    CONCLUSIONS: Based on the limited evidence available, this review found that RPD rehabilitation appear to improve OHRQoL in the short term up to 6 months, with a very low level of certainty. The long-term effect of RPD treatment on OHRQoL after 12 months is inconclusive. There is currently insufficient evidence on the effect of RPD treatment on OHRQoL. This review highlights the need for more and better quality studies.

    CLINICAL SIGNIFICANCE: Data on RPD outcomes are summarised, aiding clinicians in providing evidence-based patient-centred care that matches patients' needs and expectations. Recommendations for future research were also highlighted.

    REGISTRATION: PROSPERO CRD42022328606.

  2. Jada SR, Lim R, Wong CI, Shu X, Lee SC, Zhou Q, et al.
    Cancer Sci, 2007 Sep;98(9):1461-7.
    PMID: 17627617
    The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.
  3. Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, et al.
    EBioMedicine, 2019 Oct;48:203-211.
    PMID: 31629678 DOI: 10.1016/j.ebiom.2019.09.006
    BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

    METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

    FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P 

  4. Jia G, Ping J, Shu X, Yang Y, Cai Q, Kweon SS, et al.
    Am J Hum Genet, 2022 Dec 01;109(12):2185-2195.
    PMID: 36356581 DOI: 10.1016/j.ajhg.2022.10.011
    By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p 
  5. Ho WK, Tai MC, Dennis J, Shu X, Li J, Ho PJ, et al.
    Genet Med, 2022 Mar;24(3):586-600.
    PMID: 34906514 DOI: 10.1016/j.gim.2021.11.008
    PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.

    METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).

    RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.

    CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

  6. Shu X, Long J, Cai Q, Kweon SS, Choi JY, Kubo M, et al.
    Nat Commun, 2020 Mar 05;11(1):1217.
    PMID: 32139696 DOI: 10.1038/s41467-020-15046-w
    Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P 
  7. Yang Y, Wu L, Shu X, Lu Y, Shu XO, Cai Q, et al.
    Cancer Res, 2019 Feb 01;79(3):505-517.
    PMID: 30559148 DOI: 10.1158/0008-5472.CAN-18-2726
    DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10-7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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