Michelle A. Roesler

Periconceptional vitamin use and leukemia risk in children with Down syndrome: A children's oncology group study

Periconceptional vitamin supplementation reduces the risk of neural tube defects, and possibly may reduce the risk of certain childhood malignancies, including acute lymphoblastic leukemia (ALL). Because children with Down syndrome (DS) experience a 20‐fold higher risk of leukemia than the general population, the authors evaluated whether periconceptional vitamin supplementation reduced the risk of leukemia in children with DS.

Birth Characteristics, Maternal Reproductive History, and the Risk of Infant Leukemia: A Report from the Children's Oncology Group

Leukemias with MLL gene rearrangements predominate in infants (<1 year of age), but not in older children, and may have a distinct etiology. High birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL+, 80 MLL−, and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, pre-pregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL+ (P = 0.06), but not MLL− (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL+ (P = 0.01), but not MLL− (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies. (Cancer Epidemiol Biomarkers Prev 2007;16(1):128–34)

Comparability and Representativeness of Control Groups in a Case-Control Study of Infant Leukemia: A Report From the Children's Oncology Group

Traditionally, controls in US pediatric cancer studies were selected through random digit dialing. With declining participation and lack of nonparticipant information, random digit dialing (RDD) controls may be substandard. Birth certificate (BC) controls are an alternative, because they are population based and include data from nonparticipants. The authors examined controls collected by random digit dialing and birth certificates for a Childrens Oncology Group case-control study of infant leukemia in 1995-2006. Demographic variables were used to assess differences in RDD and BC controls and their representativeness. RDD and BC controls did not differ significantly with regard to maternal variables (age, race, education, marital status, alcohol during pregnancy) or child variables (sex, gestational age, birth weight), but they varied in smoking during pregnancy (22% RDD controls, 12% BC controls) (P = 0.05). The studys combined control group differed significantly from US births: Mothers of controls were more likely to be older (29.8 vs. 27.2 years), white (84% vs. 59%), and married (85% vs. 67%) and to have >16 years of education (37% vs. 25%). Control children were more often full term (88% vs. 81%) and heavier (3,436 vs. 3,317 g). Finally, participating BC mothers were likely to be older and to have more education than nonparticipants. Thus, the studys control groups were comparable but differed from the population of interest.

Nonsteroidal Anti-inflammatory Drug and Acetaminophen Use and Risk of Adult Myeloid Leukemia

Background: Little is known about the causes of adult leukemia. A few small studies have reported a reduced risk associated with regular use of nonsteroidal anti-inflammatory drugs (NSAID). Methods: In a population-based case–control study, we evaluated analgesic use among 670 newly diagnosed myeloid leukemia cases [including 420 acute myeloid leukemias (AML) and 186 chronic myeloid leukemias (CML)] and 701 controls aged 20 to 79 years. Prior use of aspirin, ibuprofen, acetaminophen, other NSAIDs, and COX-2 inhibitors was assessed and included frequency, duration, and quantity. ORs and 95% CIs were calculated using unconditional logistic regression adjusting for potential confounders. Results: Regular/extra strength aspirin use was inversely associated with myeloid leukemia in women (OR = 0.59, 95% CI = 0.37–0.93) but not in men (OR = 0.85, 95% CI = 0.58–1.24). In contrast, acetaminophen use was associated with an increased risk of myeloid leukemia in women only (OR = 1.60, 95% CI = 1.04–2.47). These relationships were stronger with increasing dose and duration. When stratified by leukemia type, aspirin use was inversely associated with AML and CML in women. No significant overall associations were found with ibuprofen or COX-2 inhibitors for either sex; however, a decreased risk was observed with other anti-inflammatory analgesic use for women with AML or CML (OR = 0.47, 95% CI = 0.22–0.99; OR = 0.31, 95% CI = 0.10–0.92, respectively). Conclusions: Our results provide additional support for the chemopreventive benefits of NSAIDs, at least in women. Because leukemia ranks fifth in person-years of life lost due to malignancy, further investigation is warranted. Impact: NSAIDs may reduce, whereas acetaminophen may increase, myeloid leukemia risk in women. Cancer Epidemiol Biomarkers Prev; 20(8); 1741–50. ©2011 AACR.

Infant leukemia and parental infertility or its treatment: a Children's Oncology Group report

BACKGROUND Little is known about the potential risk factors for infant leukemia. With its very young age at diagnosis, exposures occurring in the perinatal period are suspected. Parental infertility and infertility treatment have been studied with regard to childhood cancer in general, but rarely in individual cancer subtypes. METHODS A case-control study of infant leukemia was conducted through the Childrens Oncology Group, including cases diagnosed from January 1996 to December 2006 and controls selected through random digit dialing and birth certificate tracing. Maternal phone interviews were conducted to obtain information about infertility, infertility treatment and demographic factors. All cases as well as subgroups defined by mixed lineage leukemia (MLL) translocation status and leukemia subtype were examined. Statistical analysis was performed using multivariate logistic regression models. RESULTS No significant associations between infertility or its treatment and combined infant leukemia were found. In subgroup analyses, there was a significant increase in the risk of MLL--leukemia for children born to women not trying to conceive compared with those trying for <1 year for all types combined [odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.01-2.59] and for acute lymphoblastic leukemia (OR = 2.50, 95% CI = 1.36-4.61). CONCLUSIONS There were no positive associations between parental infertility or infertility treatment and infant leukemia. While this is the largest study to date, both selection and recall bias may have impacted the results. However, for infant leukemia, we can potentially rule out large increases in risk associated with parental infertility or its treatment.

Infant leukemia and congenital abnormalities: A Children's Oncology Group study†

Leukemia in infants is rare and has not been well studied apart from leukemia in older children. Differences in survival and the molecular characteristics of leukemia in infants versus older children suggest a distinct etiology, likely involving prenatal factors.

Obesity over the life course and risk of acute myeloid leukemia and myelodysplastic syndromes

BACKGROUND Overweight and obesity are known risk factors for a number of cancers, with recent evidence suggesting that risk of hematologic cancer is also increased in obese individuals. We evaluated associations between body mass index (BMI) at differing time points during the life course in population-based case control studies of acute myeloid leukemia (AML) and myelodysplatic syndromes (MDS). METHODS Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State drivers license/identification card list. BMI was calculated using self-reported height and weight at ages 18, 35, and 50 years and two years prior to interview, and categorized as normal (18.5-25 kg/m(2)), overweight (25-29.9 kg/m(2)), obese class I (30-34.9 kg/m(2)), and obese class II/III (35+ kg/m(2)). All analyses were stratified by sex. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS We included 420 AML cases, 265 MDS cases and 1388 controls. Obesity two years prior to diagnosis was associated with AML in both males and females (OR=2.22, 95% CI 1.28, 3.85 and OR=1.85, 95% CI 1.08, 3.15 for BMI≥35 vs. BMI 18.5-24.9, respectively). In contrast, associations between obesity and MDS were observed only in females. Weight change in adulthood was not consistently associated with either outcome. CONCLUSION Our results extend the emerging literature suggesting that obesity is a risk factor for hematologic malignancy and provide evidence that that the association remains regardless of timing of obesity. Obesity in adulthood is a modifiable risk factor for both MDS and AML.

Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study

Benzene exposure is one of the few well‐established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) using population‐based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota drivers license/identification card list. Chemical exposures were measured by self‐report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR = 1.77, 95% CI 1.19, 2.63 and OR = 2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR = 2.05, 95% CI 1.15, 3.63 and OR = 2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions and coal dust were associated with AML (range ORs = 2.68–4.03), while no association was seen between these exposures and MDS (range ORs = 0.57–1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population‐based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases.

Self-report versus medical record – perinatal factors in a study of infant leukaemia: a study from the Children’s Oncology Group

In a case-control study of infant leukaemia, we assessed agreement between medical records and mothers self-reported pregnancy-related conditions and procedures and infant treatments. Interview and medical record data were available for 234 case and 215 control mothers. Sensitivity, specificity and predictive values for maternal report were estimated for case and control mothers separately, taking the medical record as correct. For most perinatal conditions, sensitivity and specificity were over 75%. Low sensitivity was observed for maternal protein or albumin in the urine (cases: 12% [95% exact confidence interval (CI) 8%, 18%]; controls: 11% [95% CI 7%, 17%]) and infant supplemental oxygen use (cases: 25% [95% CI 11%, 43%]; controls: 24% [95% CI 13%, 37%]). Low specificity was found for peripheral oedema (cases: 47% [95% CI 37%, 58%]; controls: 54% [95% CI 43%, 64%]). Sensitivity for maternal hypertension appeared much lower for cases (cases: 46% [95% CI 28%, 66%]; controls: 90% [95% CI 70%, 99%]; P = 0.003). We did not detect other case-control differences in recall (differentiality), even though the average time between childbirth and interview was 2.7 years for case and 3.7 years for control mothers. Many conditions exhibited notable differences between interview and records. We recommend use of multiple measurement sources to allow both cross-checking and synthesis of results into more accurate measures.

Feasibility of neonatal dried blood spot retrieval amid evolving state policies (2009-2010): a Children's Oncology Group study.

Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged ≤21 years diagnosed from 1998 to 2007 at randomly selected Childrens Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged ≥18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups.