Trends in childhood acute lymphoblastic leukemia in Western Australia, 1960-2006.

Increases in the incidence of childhood acute lymphoblastic leukemia (ALL) have been reported in some countries, while other reports from similar geographical regions have indicated stable rates. The reasons for the discrepancies have been debated in the literature, with the focus on whether the observed increases are "real" or an artifact resulting from improvements in diagnosis, case ascertainment and population coverage over time. We used population-based data from Western Australia to investigate trends in the incidence of childhood ALL between 1960 and 2006. Age-standardized incidence rates (ASRs) and rate ratios (indicating annual percent change) were estimated using Poisson regression. Between 1960 and 2006, the ASR was 3.7 per 100,000 person-years, with an annual percent increase of 0.40% (95% CI: -0.20, 1.00). Between 1982 and 2006, the ASR was 3.8, with an annual percent increase of 0.80% (95% CI = -0.70 to 2.30). This increased to 1.42% (95% CI: -0.30, 3.0) when a sensitivity analysis was undertaken to assess the effect of excluding the final 2 years of data. Annual increases of 3.7% (95% CI: -0.50, 8.00) among children aged 5-14 years, and of 3.10% (95% CI: 0.50, 5.70) in girls, were observed for this latter period. These results were supported by national Australian incidence data available for 1982-2003. There may have been a small increase in the incidence of ALL since 1982 among girls and older children, but an overall increase appears unlikely. No impact of folate supplementation or fortification is apparent.

Buccal DNA collection: comparison of buccal swabs with FTA cards.

Collection and analysis of DNA, most commonly from blood or buccal cells, is becoming more common in epidemiologic studies. Buccal samples, which are painless to take and relatively easily collected, are often the preferred source. There are several buccal cell collection methods: swabs, brushes, mouthwash, and treated cards, such as FTA or IsoCode cards. Few studies have systematically compared methods of buccal cell collection with respect to DNA yield and amplification success under similar conditions. We compared buccal DNA collection and amplification using buccal swabs and FTA cards in 122 control subjects from our Australian case-control study of childhood acute lymphoblastic leukaemia. Buccal DNA was quantified using a real-time PCR for beta-actin and genotyped at the loci of three polymorphisms (MTHFR 677C>T, ACE I/D, and XPD 1012G>A). PCR was successful with DNA from buccal swabs for 62% to 89% of subjects and from FTA cards for 83% to 100% of subjects, depending on the locus. The matched pair odds ratios (95% confidence interval) comparing success of FTA cards with buccal swabs are as follows: MTHFR 677C>T using PCR-RFLP, 12.5 (11.6-13.5) and using real-time PCR, 130.0 (113.1-152.8); ACE I/D using PCR-amplified fragment length polymorphism, 3.36 (3.2-3.5); XPD 1012G>A using real-time PCR, 150.0 (132.7-172.3). FTA cards are a robust DNA collection method and generally produce DNA suitable for PCR more reliably than buccal swabs. There are, however, technical challenges in handling discs punched from FTA cards that intending users should be aware of.

The association between behavior and genotype in Rett syndrome using the Australian Rett Syndrome Database.

This study compared the behavior profile of cases in the Australian Rett Syndrome Database (ARSD) with those in a British study using the Rett Syndrome Behavior Questionnaire (RSBQ) and then examined behavioral patterns as measured by the RSBQ by genetic status. There were 145 Australian cases meeting the criteria for the first arm of the study and 135 for the second arm. Comparison of the scores obtained from the British and Australian cohorts indicated that the RSBQ was a satisfactory measure for describing behaviors in Rett Syndrome (RS). Overall, there were some differences among the behavior patterns of cases with the well-known common mutations. Fear/anxiety was more commonly reported in those with R133C and R306C. Those with the R294X mutation were more likely to have mood difficulties and body rocking but less likely to have hand behaviors and to display repetitive face movements. In contrast, hand behaviors were more commonly reported in those with R270X or R255X. We found the RSBQ is an appropriate instrument for measuring behavior in girls with RS. Some behaviors differ according to genetic mutation but there is both inter and intra mutation variation in behavior and there is a need for larger studies involving international collaboration to improve statistical power.

Genotype and early development in Rett syndrome: the value of international data.

BACKGROUND: Rett syndrome is a neurodevelopmental disorder mostly affecting females and caused by mutations in the MECP2 gene. Originally the syndrome was characterised as having a normal prenatal and perinatal period with later regression. Previous work has speculated that the girl with Rett syndrome may not be normal at birth. AIMS: to examine whether early development between birth and ten months varies by genotype in Rett syndrome. METHODS: cases were sourced from two databases, the Australian Rett Syndrome Database (est. 1993) and the newly formed InterRett - IRSA Rett Phenotype Database. Data available on 320 cases included information provided by parents on perinatal problems, early developmental behaviour and mobility. Problem scores, mobility scores and a total composite score for each mutation were generated and compared. RESULTS: overall, 58% of respondents noted unusual behaviour during the first six months and 70.6% from the period between 6 and 10 months of life. Statistically significant differences were detected between some of the common mutations. Infants with R294X (P=0.05) and R133C (P=0.03) were less likely than those with R255X to have problems in the perinatal period. The most severe profile overall for early development was associated with mutations R255X and R270X. CONCLUSION: This is the largest study to date examining the effects of individual mutations in Rett syndrome. With the ongoing case ascertainment and expansion of InterRett, sample size will increase rapidly and provide improved statistical power for future analyses. Results from this study will contribute to understanding the mechanism of early development in Rett syndrome and determining if and at which time(s) early intervention might be feasible.