United Kingdom Children Research Articles

Prescription drug use during pregnancy and risk of childhood cancer – Is there an association?

In economically developed countries up to 90% of women are prescribed medications, including vitamins and supplements, during pregnancy. Whilst a number of adverse health outcomes in their offspring have been related to prescription drug use, associations with childhood cancer are less clear and most investigations have been reliant on maternal self-report. With a view to providing new insight we investigated maternal prescription drug use and risk of childhood cancer primary care medical records collected as part of the United Kingdom Childhood Cancer Study, a national population-based case–control study conducted between 1991 and 1996. There was evidence that mothers of children with acute lymphoblastic leukaemia (OR 1.36, 95% CI 1.14–1.63), medulloblastoma (OR 1.79, 95% CI 1.00–3.22) and Wilms tumour (OR 1.79; 95% CI 1.05–3.04) were more likely to have been prescribed iron when compared to mothers of controls. In addition, systemic anti-infectives were positively associated with acute myeloid leukaemia (OR 1.58, 95% CI: 1.05–2.38) and rhabdomyosarcoma (OR 1.80, 95% CI 1.03–3.16), and analgesic use (NO2B) was positively associated with Hodgkin lymphoma (OR 5.02, 95% CI 2.16–11.82) and neuroblastoma (OR 1.99, 95% CI 1.07–3.69). Whilst our findings suggest that maternal use of antibiotics, iron, and nervous system drugs during pregnancy may be associated with some childhood cancer subtypes these associations need to be confirmed elsewhere. Unravelling the mechanisms that may underpin these associations is complex and research is needed to determine whether they are directly related to the drugs themselves, or the illnesses for which they were prescribed.

Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics.

SummaryThe impact of thiopurine methyltransferase (TPMT) genotype on thiopurine dose intensity, myelosuppression and treatment outcome was investigated in the United Kingdom childhood acute lymphoblastic leukaemia (ALL) trial ALL97. TPMT heterozygotes had significantly more frequent cytopenias and therefore required dose adjustments below target levels significantly more often than TPMT wild‐type patients although the average dose range was similar for both genotypes. Event‐free survival (EFS) for patients heterozygous for the more common TPMT*1/*3A variant allele (n = 99, 5‐year EFS 88%) was better than for both wild‐type TPMT*1/*1 (n = 1206, EFS 80%, P = 0·05) and TPMT*1/*3C patients (n = 17, EFS 53%, P = 0·002); outcomes supported by a multivariate Cox regression analysis. Poor compliance without subsequent clinician intervention was associated with a worse EFS (P = 0·02) and such non‐compliance may have contributed to the poorer outcome for TPMT*1/*3C patients. Patients prescribed escalated doses had a worse EFS (P = 0·04), but there was no difference in EFS by dose intensity or duration of cytopenias. In contrast to reports from some USA and Nordic trials, TPMT heterozygosity was not associated with a higher rate of second cancers. In conclusion, TPMT*1/*3A heterozygotes had a better EFS than TPMT wild‐type patients. Thiopurine induced cytopenias were not detrimental to treatment outcome.

Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011

AbstractThe effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands.

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

AbstractAlthough infection is the major cause of treatment-related mortality (TRM) in childhood acute lymphoblastic leukemia, factors associated with infection-related mortality (IRM) are poorly understood. To address this, we report an analysis of all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was 2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249 trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight percent of cases were associated with bacterial infection (64% Gram-negative) and 20% with fungal infection. Down syndrome was the most significant risk factor for IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04), as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24-3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly, patients with Down syndrome were at significantly higher risk for IRM during maintenance (P = .048). Our results confirm Down syndrome as a major risk factor for IRM. Enhanced supportive care and prophylactic antibiotics should be considered in high-risk patient groups and during periods of increased risk. This study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119.

Estimation of food portion sizes frequently consumed by children 3-6 years old in Japan.

No study has documented Japanese children's food portion sizes. Since this information is essential to establish valid measurement tools and effective education methods for dietary intake, we measured them using one-day, semi-weighed diet records (DRs) for 489 Japanese children aged 3-6 y. Each food's frequency of appearance on the DRs was counted. If a child consumed a certain food more than once per day, an average weight for that food was calculated and used in the portion size calculation as that child's representative value. In total, 67 food items were consumed by twenty or more children. We calculated the mean, standard deviation, median, minimum, and maximum portion size values for these food items. In addition to these 67 items, Chinese noodles and water were included in the analysis. The most frequently consumed food was well-milled rice (mean portion size for rice=79 g), which was consumed by 350 children, followed by soy sauce (4 g), eggs (26 g), and carrots (9 g). Among the five most frequently consumed foods, portion sizes of rice and pork but not milk, eggs, or carrots significantly increased with age, height, and weight. In multivariate linear regression analysis, however, the significant relationships between rice portion size and age were not observed. Regarding pork, only the relationship with height was significant. A sex difference was detected in the rice and milk portion sizes. Most of portion sizes observed here were apparently smaller than those reported among United Kingdom children. This study provides important basic information for the implementation of quantitative nutritional research and educational efforts for Japanese preschool children.

Surgical complications after immediate nephrectomy versus preoperative chemotherapy in non-metastatic Wilms' tumour: Findings from the 1991–2001 United Kingdom Children's Cancer Study Group UKW3 Trial

PurposeTo compare surgical complication rates after immediate nephrectomy versus delayed nephrectomy following preoperative chemotherapy in children with non-metastatic Wilms’ tumour enrolled in UKW3, both in randomised patients and in those for whom the treatment approach was defined by parental or physician choice. MethodsRecords for all patients enrolled into UKW3 were reviewed. Any record of tumour rupture or surgical complication was extracted and comparisons made between the two treatment strategies in both populations of randomised and non-randomised patients. ResultsOf 525 children enrolled, 205 patients were randomised to either immediate nephrectomy (n=103) or pre-operative chemotherapy followed by delayed nephrectomy (n=102). Of the 320 children not randomised, data were available on 189 cases treated with immediate nephrectomy and 103 treated with pre-operative chemotherapy. There were significantly fewer surgical complications in randomised children given pre-operative chemotherapy before surgery compared to children undergoing immediate nephrectomy (1% vs. 20.4%, P<0.001); this difference was most marked for tumour rupture (0% vs. 14.6%, P<0.001). ConclusionsDelayed nephrectomy for Wilms’ tumour, preceded by pre-operative chemotherapy was associated with fewer surgical complications compared with immediate nephrectomy.

The United Kingdom Children’s Laureate: The Story So Far

Britain’s Children’s Laureate Scheme has now been running for 14 years. This article asks Quentin Blake, Anne Fine, Michael Morpurgo, Jacqueline Wilson, Anthony Browne, Michael Rosen and Julia Donaldson for their views on their own experience of taking up this post. It concludes with a discussion of the recurring issues raised by these Laureates along with a look at possible future developments.

Infectious Illness in Children Subsequently Diagnosed With Acute Lymphoblastic Leukemia: Modeling the Trends From Birth to Diagnosis

Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying children's infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991-1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio.

The cultural context of care‐giving: qualitative accounts from South Asian parents who care for a child with intellectual disabilities in the UK

PurposeThis study aims to explore the cultural context of care‐giving amongst South Asian communities caring for a child with intellectual disabilities in the United Kingdom.Design/methodology/approachIn the context of the United Kingdom's Children's Intellectual Disability Services, the study set out to develop a culturally sensitive account of Sikh and Muslim parents' experiences of caring for a child with intellectual disabilities. Focus groups were conducted with parents from Sikh and Muslim support groups who were all accessing intellectual disability services for their children. Transcripts were analyzed using interpretative phenomenological analysis, a qualitative technique.FindingsThree master themes emerged from the analysis which were: Making sense of the disability; Feeling let down by services and Looking to the future. These themes reinforce findings from previous research particularly in relation to difficulties when making sense of the disabilities and difficult interactions with services.Practical implicationsThe study makes recommendations for service delivery to ethnic minority groups including being aware of intra‐group variations in the interpretations and responses of South Asian parents.Originality/valueUltimately, the study makes recommendations for developing culturally sensitive support and interventions for ethnic minority groups which is important given the increase in multi‐ethnic populations in the UK.

Long-term outcome for immune suppression and immune related lymphoproliferative disorder: prospective data from the United Kingdom Children's Leukaemia and Cancer Group registry 1994–2004

Prospective national registry data on 98 patients were studied to determine the long-term outcome of immune related lymphoproliferative disease (LPD) and define prognostic factors. Seventy-three developed LPD following organ transplant (26 liver, 21 heart, 15 kidney, nine bone marrow [BM], two bowel). Twenty-five had non-transplant related immunosuppression. Age was 1.1–17 years (median 8.6). Fifty-eight patients had lymphomatous, 21 systemic and 17 lymphadenopathic disease. Sixty (73%) were disseminated and 22 (27%) localized. Thirty-three (54%) were monoclonal. Seventy-three (83%) were Epstein–Barr virus (EBV) positive. Median follow-up was 7.6 years. LPD developed earlier after liver and BM as compared to heart or kidney transplant. Five-year overall survival (OS) was 58%. Prognosis was best after liver and kidney transplant (OS >77%). Mortality was higher following heart (2.5 times) and BM transplant (5 times). Adverse prognostic factors were disseminated or lymphomatous disease and lack of reduction of immunosuppression. With appropriate reduction of immunosuppression, rituximab and low-dose chemotherapy, long-term survival is high.

Maintenance of Immune Response throughout Childhood following Serogroup C Meningococcal Conjugate Vaccination in Early Childhood

The objectives of this study were to evaluate the kinetics of antibody decline through childhood in a longitudinal study of a single cohort following serogroup C meningococcal (MenC) vaccine immunization in early childhood and to calculate the proportion of 11 to 13 year olds with protective levels of bactericidal antibody 10 years after immunization. United Kingdom children aged 11 to 13 years in 2010 who had previously taken part in a longitudinal study at the Oxford Vaccine Group had blood samples drawn between 2001 and 2010. Sera from each time point were analyzed for the MenC serum bactericidal antibody titer using a baby rabbit complement (rSBA) assay. The median age at MenC immunization was 21 months (range, 1 year 3 months to 3 years 9 months). The MenC rSBA geometric mean titer (GMT) at age 3.5 to 5 years was 8.0 (95% confidence interval, 6.5 to 9.9; n = 287). By age 11.5 to 13.5 years, the rSBA GMT had declined to 3.3 (2.5 to 4.4; n = 98). The percentage of children with rSBA titers of ≥1:8 (the threshold for protection) also declined from 38% (35% to 41%) to 15% (12% to 19%). We concluded that MenC rSBA titers wane rapidly following vaccination in early childhood and continue to decline into the second decade of life. Since nasopharyngeal colonization in adolescents probably provides the major reservoir for MenC in the population, declining immunity in this cohort is of concern. Sustaining high levels of antibody through booster vaccination in this cohort is likely necessary to avoid a resurgence of disease in the decade ahead.

Clinical outcome in children and adolescents with Hodgkin lymphoma after treatment with chemotherapy alone – The results of the United Kingdom HD3 national cohort trial

Purpose To assess the efficacy of a standardised hybrid chemotherapy treatment programme for Hodgkin lymphoma (HL) in a national series of children and adolescents. Patients and methods The 381 assessable patients, treated between March 2000 and April 2005 in the United Kingdom Children’s Cancer Study Group trial, were reviewed to evaluate overall survival (OS), disease free survival (DFS) and deaths. Protocol treatment for stages 2–4 offered a hybrid programme of ChlVbPP (chlorambucil, vinblastine, prednisolone, procarbazine) alternating with ABVcD (doxorubicin, bleomycin, vincristine, dacarbazine). Patients with stage I disease only were offered involved field radiation alone or hybrid chemotherapy. Results With a median follow up of 5.1 years (range 0.5–8.4 years), the 5 years OS and DFS for all patients was 97% and 78%, respectively. By multivariate analysis, mediastinal and stage IV disease at presentation were the only factors that affected achieving a complete response. The 5-year DFS rate for patients with stage IV disease was 55% whilst patients with mediastinal disease had a 2-fold higher risk of an event. Conclusions This study demonstrated that multi-agent chemotherapy alone is insufficient treatment for patients with mediastinal and stage IV disease.

Long term trends introduce a potential bias when evaluating the impact of the pneumococcal conjugate vaccination programme in England and Wales

A pneumococcal conjugate vaccine (PCV7) was introduced into the United Kingdom's childhood immunisation schedule in September 2006. Evaluation of its impact on the incidence of invasive pneumococcal disease (IPD) as assessed by routine reports of laboratory-confirmed cases should take into account possible long-term trends due to factors like changes in case ascertainment. To this end, we compared pre-PCV7 trends in reported IPD incidence in England and Wales identified by blood culture with those for two other bacteraemias, Escherichia coli and non -pyogenic streptococci, for which there has not been any public health intervention. While no trend was detected in the age group 65 years and older, there was an annual increase of 3% and 11% in those aged under five years and between five and 64 years, respectively, which was similar for IPD and the other two pathogens. After PCV7 introduction, a continuing trend was only found for non-pyogenic streptococci in under five year-olds. These trends in the incidence for bacteraemias for which there has been no intervention could suggest that there have been changes in case ascertainment because of increased reporting or blood culturing. Accounting for them will improve the evaluation of the impact of PCV7 on IPD.

Renal Tumors in Children Aged 10–16 Years: A Report from the United Kingdom Children's Cancer and Leukaemia Group

Wilms tumor is the most common renal tumor of childhood. However, other epithelial, mesenchymal, and neuroectodermal neoplasms may also arise in the kidney during childhood, several of which show specific age distributions; in the 1st year of life, mesoblastic nephroma and rhabdoid tumor are more common, whereas renal cell carcinoma, primitive neuroectodermal tumor, and anaplastic Wilms tumors are relatively more frequent in older children and adolescents. The aim of this study is to describe the spectrum of renal tumors in children aged 10-16 years using data from 1492 patients registered in the UK Wilms Tumour 3 Trial (1991-2001) and International Society of Paediatric Oncology Wilms Tumour Trial 2001 (2002-2008) clinical trials of renal tumors in childhood. There were 67 (4.6%) tumors in children aged 10-16 years: 50 Wilms tumors (74.6%), 10 (14.9%) renal cell carcinomas, 3 (4.5%) renal medullary carcinomas, 2 (3%) primitive neuroectodermal tumors, 1 clear cell sarcoma of kidney, and 1 desmoplastic small round cell tumor. Fourteen percent of the Wilms tumors in this age group had diffuse anaplasia. Among the 10 renal cell carcinomas, 4 were associated with t(Xp-11.2), 3 were of papillary type II, 1 was papillary type I, 1 was clear cell type, and 1 was unclassified. Five-year overall survival for Wilms tumor was 63% (43% for anaplastic tumors), significantly lower than reported overall survival for all pediatric Wilms tumors. Only 40% of patients with renal cell carcinoma survived, and all patients with other tumors died.

Data Point to Genetic Etiology for Severe Antisocial Behavior

Data Point to Genetic Etiology for Severe Antisocial Behavior

Mesoblastic nephroma: A report of the United Kingdom children's cancer and leukaemia group (CCLG)

Mesoblastic nephroma (MN) is a rare tumour which occurs mainly in early infancy and for which primary nephrectomy is the treatment of choice. This study aimed to assess surgical complications and outcomes in this patient group and to re-evaluate the age threshold of 6 months for recommending primary nephrectomy. A retrospective file review of all cases of MN registered in UK Children's Cancer and Leukaemia Group renal tumour trials between October 1991 and March 2008. Data from the trials were compared with data held by the National Registry of Childhood Tumours, Oxford. Forty-seven (3.5%) confirmed cases of MN were found among 1346 registered renal tumours. Median age at diagnosis was 30 days (range birth-3.8 years). MN was significantly more common in the first 3 months of life compared to between 3 and 6 months (33 vs. 2 cases). Seven cases occurred between 6 months and 1 year and only five cases occurred beyond 1 year of age. There was a significant difference in the age of diagnosis by histological subtype. There were 11 complications in the series; no registered patient developed a recurrent tumour; and all were alive at last follow-up. Outcome for children with MN is excellent at all ages, with little indication for adjuvant chemotherapy. Children presenting at <3 months of age, should be treated by primary nephrectomy. In those presenting aged >3 months, alternative diagnoses should be considered, especially in the presence of surgical risk factors.

Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study

Objective To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days).Design Case-control study.Setting England and Wales.Participants 2690...

‘Coming Out Tales’: Adult Sons and Daughters' Feelings About Their Gay Father's Sexual Identity

Australian and New Zealand Journal of Family TherapyVolume 31, Issue 4 p. 338-339 ‘Coming Out Tales’: Adult Sons and Daughters' Feelings About Their Gay Father's Sexual Identity Damian McCann, Corresponding Author Damian McCann Child and Adolescent Mental Health, Edgware Community Hospital and Associate Pink Therapy Services, London, United KingdomChild and Adolescent Mental Health, Edgware Community Hospital and Associate Pink Therapy Services, London, United Kingdom. E-mail: [email protected]Search for more papers by this author Damian McCann, Corresponding Author Damian McCann Child and Adolescent Mental Health, Edgware Community Hospital and Associate Pink Therapy Services, London, United KingdomChild and Adolescent Mental Health, Edgware Community Hospital and Associate Pink Therapy Services, London, United Kingdom. E-mail: [email protected]Search for more papers by this author First published: 29 April 2013 https://doi.org/10.1375/anft.31.4.338Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume31, Issue4December 2010Pages 338-339 RelatedInformation

Childhood cancer survival: A report from the United Kingdom Childhood Cancer Study

Background: Improvements in diagnostic approaches and refinements to treatment protocols have resulted in 5-year survival levels above 70% for children diagnosed with cancer in economically developed parts of the world. For some cancers, including leukaemia and tumours of the central nervous system, age and sex have been identified as important prognostic indicators. Methods: We examined long-term survival, and affects of age and sex, in a population-based case–control study. Children (0–14 years) newly diagnosed with cancer were ascertained between 1991 and 1996 ( n = 4433). Follow-up information was obtained from the National Health Service (NHS) Information Centre for Health and Social Care which records all exits from the NHS including deaths. Results: For all cancer diagnoses combined, 5-year survival was 72.7% dropping to 67.9% at 15 years. As expected, survival differed between diagnostic subtypes ranging from 38.1% for intracranial embryonal tumours to 96.2% for Hodgkin lymphoma. Compared to girls, boys diagnosed with acute lymphoblastic leukaemia were at a higher risk of dying (RR = 1.26, 95% CI 1.03–1.53), whereas boys diagnosed with an intracranial embryonal tumour were at a lower risk of death (RR = 0.63, 95% CI 0.43–0.91). Conclusion: Our initial findings are consistent with previous reports, and highlight the importance of considering differences by age and sex. The completeness and population-based nature of the original case–control study is an important feature which will provide the basis for future more detailed investigations linking disease determinants to outcome.

Acute lymphoblastic leukaemia in children – is there a role for MTHFR?

Over the last 10 years genetic variation in folate metabolism has received considerable scientific attention, but findings have been inconsistent, with many studies based on small numbers. Koppen et al (2010) recently reported on a meta-analysis of 14 studies that had investigated genetic polymorphisms in enzymes involved in folate metabolism in relation to both childhood and adult acute lymphoblastic leukaemia (ALL), concluding that both MTHFR 677 C>T and MTHFR 1298A>C were likely to be associated with decreased susceptibility to ALL in childhood. We were however, somewhat surprised to see the authors combined data from children and adults in the same plot, despite the fact that two previous meta-analyses, neither of which were referenced by Koppen et al (2010), stratified their data by diagnostic age (Pereira et al, 2006; Zintzaras et al, 2006). Indeed, the meta-analysis plots of childhood ALL (Figures 1 and ​and22 reproduced from Koppen et al, 2010) included two studies that contained no data on children at all (Skibola et al, 1999; Gemmati et al, 2004) as well as one study that comprised both children and adults (Chiusolo et al, 2004). Whilst this was acknowledged in the text in the case of the study by Gemmati et al (2004), no such recognition was afforded our ownUKstudy (Skibola et al, 1999). Moreover several published studies where no association with MTHFR 677 was observed are missing from the review, including data from Canada (Krajinovic et al, 2004)(n = 270), Turkey (Balta et al, 2003) (n = 144) and Slovenia (Petra et al, 2007) (n = 68). Fig. 1 MTHFR 677CT and susceptibility to childhood ALL reproduced from Koppen et al, 2010. Fig. 2 MTHFR 1298AC and susceptibility to childhood ALL, reproduced from Koppen et al, 2010. From their comprehensive meta analysis of 4894 individuals Pereira et al (2006) concluded that whilst the MTHFR 677 polymorphism is important for risk of ALL, it is confined to adults. This is supported by recent data from the largest study to date, which included 939 children with ALL recruited into the United Kingdom Childhood Cancer Study (http://www.UKCCS.org) (Lightfoot et al, 2010). Given the missing childhood data and the inclusion of adult data, we believe that the conclusion for a protective role for MTHFR among children drawn by the authors of the recent meta-analysis (Koppen et al, 2010), is misleading.