MATERIALS AND METHODS: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing.
RESULTS: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC.
CONCLUSIONS: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.
MATERIALS AND METHODS: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
RESULTS: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population.
CONCLUSIONS: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.
AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status.
MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase.
RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients.
CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.
METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
OBJECTIVE: To determine the value of uvulo-palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem subitum (ES) due to human herpesvirus 6 (HHV 6) infection.
STUDY DESIGN: A case-control study of 20 febrile children with UPJ ulcers versus 26 febrile children without UPJ ulcers. These children were followed up for any development of ES and investigated for human herpesvirus 6 (HHV 6) as the causative agents of the febrile episodes.
RESULTS: In this study, 20 out of 46 febrile children aged 3 months to 3 years with UPJ ulcers were virologically and/or serologically confirmed to be due to primary HHV 6 infection. The rest of the 26 children without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers, only 17 of the 19 children with adequate follow-up till subsidence of fever developed ES. None of the 26 children without UPJ ulcers developed ES.
CONCLUSION: Statistically, there was a significant association of UPJ ulcers as an early sign of ES with a positive predictive value of 89.5% and negative predictive value of 100%. This finding also suggests that the presence of UPJ ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6 infection.
METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity.
RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life.
CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.
METHODS: Twenty-nine children in each group, matched for age, sex and ethnicity, were assessed using the Glasgow outcome Scale (GOS), Weschler Intelligence Scale for Children (WISC-III), Movement Assessment Battery for Children (Movement ABC), Wide Range Assessment of Learning and Memory (WRAML) and a standardised neurological examination 6 months post-injury. Parental reporting of pre- and post-injury behaviour was documented using the Child Behaviour Checklist (CBCL).
RESULTS: Seven (24.1%) children with sCHI and three (10.3%) orthopaedic controls had residual motor deficits. Three (10.3%) children with sCHI and none in the other groups faced problems with independent ambulation. Twenty-seven (93.1%) of those with sCHI and all children in the other groups had GOS scores of good recovery or moderate disability. Twenty-two (81.5%) sCHI, five (18.5%) mCHI and one (3.7%) orthopaedic control reported a deterioration in school performance. MANOVAS identified a significant injury group effect for performance skills (P = 0.007), verbal skills (P = 0.002), memory and learning (P = 0.001) and motor skills (P = 0.001). Repeated measures ANOVA for pre- and post-injury CBCL scores showed significant differences related to somatic complaints (P = 0.004), problems of socialising (P = 0.003), delinquency (P = 0.004), aggressiveness (P = 0.010), thought (P < 0.001) and attention (P < 0.001). Post-hoc univariate analysis showed the significant differences were between that of the sCHI children and the other two groups.
CONCLUSION: Although most sCHI children seemed to have made good physical recovery, there were cognitive, motor, memory and learning difficulties and behavioural problems concomitant with a deterioration in school performance compared with those with lesser or no head injury. This highlights the need for better integrated rehabilitation services to enable a gradual return into mainstream school.