METHODS: This is a meta- analysis study, following the preferred reporting items for systematic reviews and meta- analyses (PRISMA). Relevant studies were searched in the health related electronic databases. Methodological quality of the included studies were assessed using the Newcastle-Ottawa Scale. For individual studies, odds ratio (OR) and its 95%confidence interval (CI) were calculated to assess the strength of association between IL10 polymorphisms (- 1082 A > G, -819C > T, - 592 A > C) and the risk of periodontitis. For pooling of the estimates across studies included, the summary OR and its 95% CIs were calculated with random-effects model. The pooled estimates were done under four genetic models such as the allelic contrast model, the recessive model, the dominant model and the additive model. Trial sequential analysis (TSA) was done for estimation of the required information size for this meta-analysis study.
RESULTS: Sixteen studies were identified for this review. The included studies were assessed to be of moderate to good methodological quality. A significant association between polymorphism of IL10-1082 A > G polymorphism and the risk of chronic periodontitis in the non-Asian populations was observed only in the recessive model (OR,1.42; 95% CI:1.11, 1.8,I2: 43%). The significant associations between - 592 A > C polymorphism and the risk of aggressive periodontitis in the non-Asian populations were observed in particular genetic models such as allele contrast (OR, 4.34; 95%CI:1.87,10.07,I2: 65%) and recessive models (OR, 2.1; 95% CI:1.16, 3.82,I2: 0%). The TSA plot revealed that the required information size for evidence of effect was sufficient to draw a conclusion.
CONCLUSIONS: This meta-analysis suggested that the IL10-1082 A > G polymorphism was associated with chronic periodontitis CP risk in non-Asians. Thus, in order to further establish the associations between IL10 (- 819 C > T, - 592 A > C) in Asian populations, future studies should include larger sample sizes with multi-ethnic groups.
METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.
RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values
METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.
RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P
OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.
METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.
RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).
CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.
MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.
CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.
METHODS: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.
RESULTS: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.
CONCLUSION: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.