Maternal exposure to ambient air temperature during pregnancy and early childhood pneumonia

BackgroundPneumonia has been widely recognized as the leading cause of death in children worldwide, but its etiology still remains unclear.ObjectiveWe examined the association between maternal exposure to ambient air temperature during pregnancy and lifetime pneumonia in the offspring.MethodsWe conducted a cohort study of 2598 preschool children aged 3–6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed using questionnaire. We backwards estimated each child's exposure to air temperature during prenatal and postnatal periods. Multiple regression model was used to examine the association between childhood pneumonia and exposure to air temperature in terms of odd ratios (OR) and 95% confidence interval (CI).ResultsPrevalence of childhood pneumonia in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal exposure to air temperature, with adjusted OR (95% CI) = 1.77 (1.23–2.54) for an interquartile range (IQR) increase in temperature, particularly during the second trimester with adjusted OR (95% CI) = 2.26 (1.32–3.89). Boys are more susceptible to the risk of pneumonia due to air temperature than girls. We further observed that maternal exposure to extreme heat days during pregnancy increased the risk of pneumonia in the offspring.ConclusionsMaternal exposure to air temperature during pregnancy, particularly the second trimester, was associated with pneumonia in the children, providing the evidence for fetal origins of pneumonia.     

Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women

BACKGROUND: Previous studies suggest that trichloroethylene (TCE) is a selective cardiac teratogen. We tested the hypothesis that the odds of maternal residence close to TCE-emitting sites would be greater among infants with congenital heart defects (CHDs) than among infants without CHDs. METHODS: We conducted a case-control study of 4025 infants, identified from hospital and birth records, born from 1997 to 1999 to Milwaukee, Wisconsin mothers. A geographic information system was used to calculate distances between maternal residences and TCE sites. We used classification tree analysis to determine appropriate values by which to dichotomously categorize mothers by TCE exposure (exposed: residence within 1.32 miles of at least one TCE site) and age (older: >/=38 years), and logistic regression to test for CHD risk factors. RESULTS: The proportion of mothers who were both older and had presumed TCE exposure was more than six-fold greater among case infants than among control infants (3.3% [8/245] versus 0.5% [19/3780]). When adjusted for other variables, CHD risk was over three-fold greater among infants of older, exposed mothers compared to infants of older, nonexposed mothers (adjusted OR, 3.2; 95% CI, 1.2-8.7). Older maternal age, alcohol use, chronic hypertension, and preexisting diabetes were each associated with CHDs (adjusted ORs, 1.9, 2.1, 2.8, 4.1; 95% CIs, 1.1-3.5, 1.1-4.2, 1.2-6.7, 1.5-11.2, respectively), but residence close to TCE sites alone was not. CONCLUSIONS: Our findings suggest that maternal age and TCE exposure interact to increase CHD risk, although the mechanism by which this occurs is unknown. A prospective study is underway to confirm this finding.     

Birth weight and other perinatal characteristics and childhood leukemia in California

Aims. We conducted a large registry-based study in California to investigate the association of perinatal factors and childhood leukemia with analysis of two major subtypes, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Methods. We linked California cancer and birth registries to obtain information on 5788 cases and 5788 controls matched on age and sex (1:1). We examined the association of birth weight, gestational age, birth and pregnancy order, parental ages, and specific conditions during pregnancy and risk of total leukemia, ALL and AML using conditional logistic regression, with adjustment for potential confounders. Results. The odds ratio (OR) per 1000 g increase in birth weight was 1.11 for both total leukemia and ALL. The OR were highest for babies weighing ≥4500 g with reference <2500 g: 1.59 (95% CI: 1.05–2.40) and 1.70 (95% CI: 1.08–2.68) for total leukemia and ALL, respectively. For AML, increase in risk was also observed but the estimate was imprecise due to small numbers. Compared to average-for-gestational age (AGA), large-for-gestational age (LGA) babies were at slightly increased risk of total childhood leukemia (OR = 1.10) and both ALL and AML (OR = 1.07 and OR = 1.13, respectively) but estimates were imprecise. Being small-for-gestational age (SGA) was associated with reduced risk of childhood leukemia (OR = 0.81, 95% CI: 0.67–0.97) and ALL (OR = 0.77, 95% CI: 0.63–0.94), but not AML. Being first-born was associated with decreased risk of AML only (OR = 0.70; 95% CI: 0.53–0.93). Compared to children with paternal age <25 years, children with paternal age between 35 and 45 years were at increased risk of total childhood leukemia (OR = 1.12; 95% CI: 1.04–1.40) and ALL (OR = 1.23; 95% CI: 1.04–1.47). None of conditions during pregnancy examined or maternal age were associated with increased risk of childhood leukemia or its subtypes. Conclusions. Our results suggest that high birth weight and LGA were associated with increased risk and SGA with decreased risk of total childhood leukemia and ALL, being first-born was associated with decreased risk of AML, and advanced paternal age was associated with increased risk of ALL. These findings suggest that associations of childhood leukemia and perinatal factors depend highly on subtype of leukemia.     

High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Family Characteristics as Risk Factors for Childhood Acute Lymphoblastic Leukemia: A Population-Based Case-Control Study

Background

To date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial “evidence.” We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL).

Methodology/Principal Findings

In this population-based nationwide matched case-control study, patients 0–14 years of age with ALL diagnosed 1991–2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05–1.31; p = 0.004), remaining stable (trend OR 1.14, 95% CI 0.99–1.31; p = 0.060) after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01–1.28, p = 0.032) and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0–14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0–4 years (OR per sibling 0.85, 95% CI 0.68–1.06; p = 0.141) and a positive trend for ALL diagnosed at age 5–9 (OR 1.34, 95% CI 1.05–1.72; p = 0.019), with some evidence for an effect modification (p-value for interaction  = 0.040).

Conclusions

As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.     

Association of maternal and index child’s diet with subsequent leukemia risk: A systematic review and meta analysis

BackgroundExploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk.MethodsMedline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood.ResultsEighteen studies of case-control design (N = 11,720 cases/18,721 controls) were included, of which nine assessed maternal dietary components, five index child’s and four both, mainly focusing on acute lymphoblastic leukemia (ALL). Statistically significant inverse estimates for ALL were found (2 studies, 413 cases, 490 controls) for fruit (OR: 0.81, 95% CI: 0.67, 0.99); vegetables (OR: 0.51, 95% CI: 0.28, 0.94); legumes (OR: 0.76, 95% CI: 0.62, 0.94); fish (OR: 0.27, 95% CI: 0.14, 0.53, among the 0–4 year old; 2 studies 215 cases, 215 controls); preconception folic acid supplementation (OR: 0.69, 95%CI: 0.50–0.95; published meta analysis plus 2 studies, 3511 cases, 6816 controls); and use of vitamins during pregnancy (OR: 0.81, 95%CI: 0.74–0.88; published meta analysis plus one study, 5967 cases, 8876 controls). The associations (2 studies) of the remaining food groups and maternal dietary supplements consumption during pregnancy as well as of childhood diet and supplements intake (2–4 studies) were non significant.ConclusionsMaternal consumption of specific food groups comprising“healthy” items of the Mediterranean diet, preconception use of folic acid and intake of vitamins during pregnancy were associated with decreased ALL risk. Further research is needed, however preferably with homogeneous dietary information and data on immunophenotypic/cytogenetic subtypes to also explore the interaction of specific macro- and micronutrients intake with gene polymorphisms.     

Altered infant feeding patterns in boys with acquired nonsyndromic cryptorchidism

BACKGROUND : Genetic and environmental factors likely influence susceptibility to nonsyndromic cryptorchidism, a common disease presenting at birth or in later childhood. We compared cases and controls to define differential risk factors for congenital versus acquired cryptorchidism. METHODS : We compared questionnaire and clinical data from cases of congenital cryptorchidism (n = 230), acquired cryptorchidism (n = 182) and hernia/hydrocele (n = 104) with a group of healthy male controls (n = 358). Potential predictor variables (p < 0.2 in univariable analysis) were included in stepwise multivariable logistic regression models. RESULTS : Temporary (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4–0.8) or exclusive (OR, 0.6; 95% CI, 0.4–0.9) breastfeeding was reduced and soy formula feeding increased (OR, 1.8; 95% CI, 1.2–2.9) in acquired but not congenital or hernia/hydrocele groups. The highest risk estimates were observed for primary soy formula feeding with limited or no breastfeeding (OR 2.5; 95% CI, 1.4–4.3; adjusted OR, 2.7; 95% CI, 1.4–5.4) in the acquired group. Primary feeding risk estimates were equivalent or strengthened when multivariable models were limited to age greater than 2 years, full‐term or not small for gestational age, or Caucasian subjects. Pregnancy complications and increased maternal exposure to cosmetic or household chemicals were not consistently associated with either form of cryptorchidism in these models. CONCLUSIONS : Our data support reduced breastfeeding and soy formula feeding as potential risk factors for acquired cryptorchidism. Although additional studies are needed, hormonally active components of breast milk and soy formula could influence the establishment of normal testis position in the first months of life, leading to apparent ascent of testes in childhood. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Perinatal and early life risk factors for childhood brain tumors: Is instrument-assisted delivery associated with higher risk?

BackgroundThe childhood peak of brain tumors suggests that early-life exposures might have a role in their etiology. Hence, we examined in the Greek National Registry for Childhood Hematological Malignancies and Solid tumors (NARECHEM-ST) whether perinatal and early-life risk factors influence the risk of childhood brain tumors.MethodsIn a nationwide case-control study, we included 203 cases (0–14 years) with a diagnosis of brain tumor in NARECHEM-ST (2010–2016) and 406 age-, sex-, and center-matched hospital controls. Information was collected via interviews with the guardians and we analyzed the variables of interest in multivariable conditional logistic regression models.ResultsInstrument-assisted delivery was associated with higher (OR: 7.82, 95%CI: 2.18–28.03), whereas caesarean delivery with lower (OR: 0.67, 95%CI: 0.45-0.99) risk of childhood brain tumors, as compared to spontaneous vaginal delivery. Maternal alcohol consumption during pregnancy (OR: 2.35, 95%CI: 1.45–3.81) and history of living in a farm (OR: 4.98, 2.40–10.32) increased the odds of childhood brain tumors. Conversely, higher birth order was associated with lower risk (OR for 2nd vs. 1st child: 0.60, 95%CI: 0.40-0.89 and OR for 3^rd vs. 1^st: 0.34, 95%CI: 0.18-0.63). Birth weight, gestational age, parental age, history of infertility, smoking during pregnancy, allergic diseases, and maternal diseases during pregnancy showed no significant associations.ConclusionsPerinatal and early-life risk factors, and specifically indicators of brain trauma, exposure to toxic agents and immune system maturation, might be involved in the pathogenesis of childhood brain tumors. Larger studies should aim to replicate our findings and examine associations with tumor subtypes.     

Exposure to electrical contact currents and the risk of childhood leukemia

The objectives of this study were to examine the association between contact current exposure and the risk of childhood leukemia and to investigate the relationship between residential contact currents and magnetic fields. Indoor and outdoor contact voltage and magnetic-field measurements were collected for the diagnosis residence of 245 cases and 269 controls recruited in the Northern California Childhood Leukemia Study (2000-2007). Logistic regression techniques produced odds ratios (OR) adjusted for age, sex, Hispanic ethnicity, mother's race and household income. No statistically significant associations were seen between childhood leukemia and indoor contact voltage level [exposure ≥90th percentile (10.5 mV): OR = 0.83, 95% confidence interval (CI): 0.45, 1.54], outdoor contact voltage level [exposure ≥90th percentile (291.2 mV): OR = 0.89, 95% CI: 0.48, 1.63], or indoor magnetic-field levels (>0.20 μT: OR = 0.76, 95% CI: 0.30, 1.93). Contact voltage was weakly correlated with magnetic field; correlation coefficients were r = 0.10 (P = 0.02) for indoor contact voltage and r = 0.15 (P = 0.001) for outdoor contact voltage. In conclusion, in this California population, there was no evidence of an association between childhood leukemia and exposure to contact currents or magnetic fields and a weak correlation between measures of contact current and magnetic fields.     

Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes.

The relationship between childhood leukemia and prenatal exposure to low-dose ionizing radiation remains debatable. This population-based case-control study investigated the association between prenatal exposure to diagnostic X-ray examinations (for different types of examinations and at different stages of pregnancy) and the risk of childhood lymphatic and myeloid leukemia. All children born and diagnosed with leukemia between 1973-1989 in Sweden (578 lymphatic and 74 myeloid) were selected as cases, and each was matched (by sex and year of birth) to a healthy control child (excluding Down's syndrome). Exposure data were abstracted blindly from all available medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. It was found that prenatal X-ray examinations resulting in direct fetal exposure were not associated with a significant overall increased risk for childhood leukemia (OR = 1.11, 95% CI 0.83-1.47), for lymphatic leukemia (OR = 1.04, 95% CI 0.77-1.40), or for myeloid leukemia (OR = 1.49, 95% CI 0.48-4.72). There was little evidence of a dose response or variation in risk by trimester of exposure or age at diagnosis. Thus X-ray examinations performed during pregnancy in the 1970s and 1980s in Sweden did not affect the risk of childhood leukemia discernibly.     

Prenatal exposure to diurnal temperature variation and early childhood pneumonia

BackgroundChildhood pneumonia is one of the leading single causes of mortality and morbidity in children worldwide, but its etiology still remains unclear.ObjectiveWe investigate the association between childhood pneumonia and exposure to diurnal temperature variation (DTV) in different timing windows.MethodsWe conducted a prospective cohort study of 2,598 children aged 3–6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed by a questionnaire administered by the parents. Individual exposure to DTV during both prenatal and postnatal periods was estimated. Logic regression models was used to examine the association between childhood pneumonia and DTV exposure in terms of odds ratios (OR) and 95% confidence interval (CI).ResultsLifetime prevalence of childhood pneumonia in preschool children in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal DTV exposure, with adjusted OR (95%CI) =1.19 (1.02–1.38), particularly during the second trimester. However, childhood pneumonia not associated with postnatal DTV exposure. Sensitivity analysis indicated that boys are more susceptible to the pneumonia risk of diurnal temperature variation than girls. We further observed that the prevalence of childhood pneumonia was decreased in recent years as DTV shrinked.ConclusionsEarly childhood pneumonia was associated with prenatal exposure to the diurnal temperature variation (DTV) during pregnancy, particularly in the second trimester, which suggests fetal origin of childhood pneumonia.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

Maternal Benzene Exposure during Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis of Epidemiologic Studies

Background

The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.

Methods

Relevant studies up to September 1^st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.

Results

Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR) with 95% confidence interval (CI) for ALL was 1.25 (1.09, 1.45) for solvent, 1.23 (1.02, 1.47) for paint, 1.42 (1.10, 1.84) for petroleum exposure, and 0.99 (0.93, 1.06) for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.

Conclusions

Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.     

Pediatric germ cell tumors and parental infertility and infertility treatment: a Children's Oncology Group report

Background

Few risk factors have been established for childhood germ cell tumors (GCT). Parental infertility and infertility treatment may be associated with GCT development but these risk factors have not been fully investigated.

Methods

A case–control study of childhood GCT was conducted through the Children's Oncology Group (COG). Cases, under the age of 15 years at diagnosis, were recruited through COG institutions from January 1993 to December 2002. Controls were obtained through random digit dialing. Information about infertility and infertility treatment along with demographic factors was collection through maternal interviews. Subgroups created by gender, age at diagnosis, and tumor location were examined separately. Statistical analysis was performed using multivariate logistic regression models.

Results

Overall, no association between GCT and infertility or its treatment was found. In subgroup analysis, females whose mothers had two or more fetal losses were found to be at increased risk for non-gonadal tumors (Odds ratio (OR) = 3.32, 95% Confidence interval (CI) = 1.12–9.88). Younger maternal age was associated with a lower risk of gonadal GCT in females (OR = 0.52, 95% CI = 0.28–0.96). There was an increased risk of all GCT and gonadal GCT in males born to older mothers (OR = 2.88, 95% CI = 1.13–7.37 and OR = 3.70, 95% CI = 1.12–12.24).

Conclusion

While no association between parental infertility or its treatment and childhood GCT was found overall, possible associations with maternal age and history of recurrent fetal loss were found in subgroups defined by gender.     

Maternal pregestational diabetes and risk of acute lymphoblastic leukemia in the offspring: A population-based study in Northern Italy

IntroductionThis population-based study aims to evaluate the association between maternal pregestational diabetes and risk of acute lymphoblastic leukemia (ALL) in the offspring.MethodsAll 241,958 children born in three Northern Italy provinces 1998–2010 were followed from birth until first cancer diagnosis (National Childhood Cancer Register), age 15 years, or 31 December 2017. We computed hazard ratio (HR) and 95% CI of ALL in relation to the presence of maternal diabetes through Cox proportional regression models.ResultsWe observed 145 cases of ALL, with a higher incidence in children born to women with pregestational diabetes compared to the others (12.4 vs 4.6). Adjusted hazard ratio of ALL was 2.6 (CI, 0.6–10.5) for maternal diabetes.DiscussionWe estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.     

Prenatal exposure to medicines and the risk of childhood brain tumor

Background: Childhood brain tumors are associated with high mortality and morbidity but little is known about its causes. About half of women use medicines when pregnant and some of the medicines commonly used might be carcinogenic. Objective: The aim with this population-based case–control study was to analyze associations between specific groups of medicines taken during pregnancy and the risk of brain tumor in the offspring. Methods: All children, up to 15 years of age, born in Sweden between 1975 and 1984 were eligible for the study. Cases (N = 512) were children diagnosed with brain tumor and controls (N = 525) were randomly selected from the Medical Birth Register. Exposure data on medicines was extracted blindly from antenatal medical records and grouped according to Anatomical Therapeutic Chemical (ATC) code. Information on maternal reproductive history was received from the Medical Birth Register. We used logistic regression to estimate associations between fetal exposure to medicines and childhood brain tumor. Results: No significant changes in risk were noted after exposure to iron supplementation, antiemetics, analgesics, antibiotics or any other main ATC group. A tendency of protective effect was seen for prenatal exposure to folic acid (adjusted OR 0.6, 95% CI 0.3–1.1). Ten children with a diagnosis of brain tumor had been exposed to β-blocking agents in fetal life as compared to two children without brain tumor (adjusted OR 5.3, 95% CI 1.2–24.8). Conclusions: In this case–control study, an increased risk of brain tumor was seen in children exposed to β-blocking agents during fetal life. However, due to the low number of exposed the interpretation of this finding should be made with caution.     

Examining the association between cigarette smoking and colorectal cancer using historical case–control data

Background: The majority of recent, well-designed studies have shown that long-term cigarette smoking increases colorectal cancer risk, but older studies with shorter durations of exposure often found no association. This study aimed to examine colorectal cancer risk by smoking exposure using data collected in the late-1950s and early-1960s. Methods: This case–control study examined colorectal cancer risk by lifetime smoking history. There were 1365 patients who visited Roswell Park Cancer Institute (RPCI) between 1957 and 1965 diagnosed with primary, incident colorectal cancers that were matched to 4096 malignancy-free controls on gender and age. Odds ratios were calculated using separate logistic regression models for each smoking exposure, while controlling for other tobacco use, county of residence, race, age, gender, and body mass index (BMI). Results: The adjusted OR for individuals who reported their greatest level of smoking to be more than 1 pack/day was 0.87 (95% CI = 0.67–1.15). Among those who smoked 42 or more years, the adjusted OR was 0.89 (95% CI = 0.68–1.15) compared to those who never smoked. For individuals who smoked more than 45 pack-years, the OR was 0.92 (95% CI = 0.72–1.19). The results did not differ significantly by gender, although men had considerably greater exposure compared to women. Results also did not differ by colorectal sub-site. Conclusion: No association was found between long-term cigarette smoking and colorectal cancer risk. These results are in accord with studies that followed cohorts throughout the 1950s and 1960s. Methodological limitations, such as missing data on covariates and the higher incidence of smoking-related illness in a hospital setting, may have contributed to the null results found in this study. Prolonged population exposure to cigarettes and perhaps a changing product may explain why more recent studies have reported a positive association between smoking and colorectal cancer.     

Risk of Childhood Overweight after Exposure to Tobacco Smoking in Prenatal and Early Postnatal Life

Objective

To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account.

Methods

From the Danish National Birth Cohort a total of 32,747 families were identified with available information on maternal smoking status in child''s pre- and postnatal life and child''s birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four groups: no exposure (n = 25,076); exposure only during pregnancy (n = 3,343); exposure only postnatally (n = 140); and exposure during pregnancy and postnatally (n = 4,188). Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds ratios using logistic regression models.

Results

Exposure to smoking only during pregnancy, or both during pregnancy and postnatally were both significantly associated with overweight at 7 years of age (OR: 1.31, 95% CI: 1.15–1.48, and OR: 1.76, 95% CI: 1.58–1.97, respectively). Analyses excluding children with low birth weight (<2,500 gram) revealed similar results. A significant prenatal dose-response relationship was found. Per one additional cigarette smoked per day an increase in risk of overweight was observed (OR: 1.02, 95% CI: 1.01–1.03). When adjusting for quantity of smoking during pregnancy, prolonged exposure after birth further increased the risk of later overweight in the children (OR 1.28, 95% CI:1.09–1.50) compared with exposure only in the prenatal period.

Conclusions

Mother''s perinatal smoking increased child''s OR of overweight at age 7 years irrespective of birth weight, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for prevention of any tobacco exposure of infants.     

Association between the Polymorphism rs3217927 of CCND2 and the Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3′UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR  =  1.84, 95% CI  =  1.14 —2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR  = 1.95, 95% CI  =  1.04–3.67), low-risk ALL (adjusted OR  =  2.09, 95% CI  =  1.13–3.87), B-phenotype ALL patients (adjusted OR  =  1.78, 95% CI  =  1.08–2.95) and T-phenotype ALL patients (adjusted OR  =  2.87, 95% CI  =  1.16–7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.     

ARID5B,IKZF1 and Non-Genetic Factors in the Etiology of Childhood Acute Lymphoblastic Leukemia: The ESCALE Study

Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.