Preconception Paternal Smoking Research Articles

Pre- and Postnatal Exposures to Tobacco Smoking and Survival of Childhood Acute Lymphoblastic and Myeloid Leukemias in California, United States.

Tobacco smoke adversely affects the prognosis of adult cancers including myeloid leukemia, but less is known in children. We evaluated whether pre- and postnatal exposures to tobacco smoke decrease 5-year survival of 1,235 childhood acute lymphoblastic leukemia (ALL) and 188 childhood acute myeloid leukemia (AML) cases derived from a population-based case-control study in California. Cases were diagnosed between 1995 and 2015 (median follow-up time of 13.2 years overall). We obtained data on tobacco smoking (before conception, during pregnancy, after birth), parental education and income, clinical features, and vital status through 2020. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality associated with smoking, adjusting for sociodemographic characteristics and risk group (ALL only). About 23% of mothers and 39% of fathers reported smoking and 130 children with ALL and 52 with AML died within 5 years. For AML, increased risks of death were observed among children whose fathers smoked before conception compared with nonsmoking fathers [HR = 1.41; 95% confidence interval (CI), 0.95-3.44 and 3.47; 95% CI, 1.37-8.81, respectively for <20 vs. ≥20 cigarettes per day; Ptrend = 0.01]. HR for child's passive smoking was 1.74, 95% CI, 0.81-3.73. Paternal preconception smoking may also reduce 5-year survival among ALL with favorable prognostic molecular subtypes (high hyperdiploidy and absence of IKZF1 gene deletion), although the associations did not reach statistical significance (Pheterogeneity = 0.07). Paternal preconception smoking decreased 5-year survival of childhood AML. Knowledge of exposure to tobacco smoking should be integrated in the treatment plan of childhood leukemias.

Paternal smoking and preterm birth: a population-based retrospective cohort study among non-smoking women aged 20\u201349\xa0years in rural China

BackgroundTo comprehensively evaluate the association of paternal smoking and preterm birth (PTB).MethodsWe performed a population-based retrospective cohort study in rural areas of China among 5,298,043 reproductive-aged couples who participated in the National Free Pre-Pregnancy Checkups Project (NFPCP), regarding outcome events that occurred in 2010–2016. Multivariate Cox proportional regression was used to estimate hazard ratio (HR) and 95% confident intervals (95%CI), and restricted cubic spline (RCS) were used to estimate the dose–response relationship.ResultsCompared to neither-smoker couples, the fully adjusted HR for PTB was 1.04 (95% CI, 1.03–1.04), 1.08 (0.96–1.22), and 1.11 (1.03–1.19) in the couples where only the female smoked, only the male smoked and both, respectively. HR of PTB for paternal smoking was 1.07 (1.06–1.07), compared with women without paternal smoking. Consistent with paternal smoking, preconception paternal smoking showed 1.07-fold higher risk of PTB (95%CI, 1.06–1.09). The multivariable-adjusted HRs of PTB were 1.05 (1.03–1.06), 1.04 (1.03–1.05), 1.05 (1.04–1.07), 1.07 (1.05–1.10) and 1.13 (1.12–1.14) for participants whose husband smoked 1–4, 5–9, 10–14, 15–19, and ≥ 20 cigarettes/day respectively, compared with participants without paternal smoking. The HRs of PTB also increased with the increment of paternal smoking and preconception paternal smoking categories (Plinear < 0.05).ConclusionsPaternal smoking and preconception paternal smoking was independently positively associated with PTB risk. The importance of tobacco control, should be emphasized during preconception and pregnancy counselling should be towards not only women but also their husband.

Analysis of Preconception Paternal Smoking and Neonatal Outcomes

Analysis of Preconception Paternal Smoking and Neonatal Outcomes

P–718 Paternal smoking in the preconception period is associated with an increased risk of spontaneous miscarriage in a dose-dependent manner: a systematic review and meta-analysis

Abstract Study question What is the association between paternal lifestyle factors in the preconception period and the risk of spontaneous miscarriage? Summary answer: Preconception paternal cigarette smoking is associated with an increased risk of spontaneous miscarriage, while no associations were found with paternal alcohol consumption and obesity. What is known already Although maternal lifestyle risk factors for miscarriage are well-established, studies on potentially contributing paternal factors remain sparse. Recently, a significant association was found between advanced paternal age and spontaneous miscarriage. Biological evidence indicates that smoking, excessive alcohol consumption and obesity may lead to sperm oxidative DNA damage, being a known risk factor for miscarriage. Study design, size, duration: Systematic review and meta-analysis. Participants/materials, setting, methods PubMed and Embase databases were searched in August 2020. Paternal factors examined were: cigarette smoking, alcohol consumption and Body Mass Index (BMI). A qualitative risk of bias assessment was performed for all included studies. Meta-analysis was performed if sufficient data was available from studies that controlled for maternal factors. PRISMA guidelines for systematic reviews were followed. Main results and the role of chance The systematic search included 3386 articles of which 11 articles met the inclusion criteria. In a meta-analysis of eight studies, paternal smoking of &amp;gt; 10 cigarettes per day in the preconception period was found to be associated with an increased risk of spontaneous miscarriage, after adjustment for maternal smoking status (1–10 cigarettes per day: 1.01, 95% CI 0.97–1.06; 11–20 cigarettes per day: 1.12, 95% CI 1.08–1.16; &amp;gt;20 cigarettes per day: 1.23, 95% CI 1.17–1.29). Based on five available studies, no clear association was found between paternal alcohol consumption and spontaneous miscarriage. No studies were retrieved that evaluated the association between paternal BMI and spontaneous miscarriage. Limitations, reasons for caution Investigating the relation between paternal lifestyle factors and spontaneous miscarriage is challenging and prone to different forms of bias, especially in retrospective studies. Wider implications of the findings: Awareness of the association between heavy paternal smoking in the preconception period and the risk of spontaneous miscarriage should be raised. More well-designed studies are needed to further investigate the effects of other paternal lifestyle factors on the risk of spontaneous miscarriage. Trial registration number Not applicable

Association between preconception paternal smoking and birth defects in offspring: evidence from the database of the National Free Preconception Health Examination Project in China.

To clarify whether preconception paternal smoking has any adverse effects on the offspring. Prospective, population-based study. Preconception registry data from the National Free Preconception Health Examination Project. Couples planning pregnancy, with complete information on preconception paternal smoking behaviour and pregnancy outcomes. The effect of questionnaire-based paternal smoking behaviour during preconception and pregnancy was assessed via logistic regression. Additionally, we performed a 1:1 case-control (birth defects versus normal pregnancy) analysis, matched for maternal province, folic acid supplementation and paternal alcohol consumption. Risk of birth defects in offspring. In total, 566439 couples with complete information on preconception paternal smoking behaviour and pregnancy outcomes were enrolled. The preconception paternal smoking rate was 28.7% (162482) overall: 8.7% (49303) stopped smoking, 13.3% (75517) decreased their smoking, and 6.6% (37662) continued smoking during early pregnancy. The risk of birth defects was higher in the continued-smoking (P<.000, odds ratio [OR] 1.87, 95% CI 1.36-2.56) and decreased-smoking groups (P=.007, OR1.41, 95% CI 1.10-1.82). In the case-control analysis, infants whose fathers stopped (P=.003, OR0.32, 95% CI 0.15-0.67) or decreased smoking (P=.000, OR 0.25, 95% CI 0.13-0.49) were at lower risk of congenital heart diseases, limb abnormalities, digestive tract anomalies and neural tube defects than those whose fathers continued smoking. Preconception paternal smoking may be associated with congenital heart diseases, limb abnormalities and neural tube defects in the offspring. Changes in smoking behaviour may reduce this risk. This study suggests that preconception paternal smoking is associated with birth defects in offspring. Changes in smoking behaviour may reduce this risk.

Preconception Paternal Smoking As a Risk Factor of Birth Defects in Offspring: Evidence from the Database of National Free Preconception Health Examination Project in China

Background: The association between paternal smoking and birth defects in offspring was indicated. However, there lacks prospective evidence to recommend father smoking quit before pregnancy for eliminating birth defects risk in his offspring. This study aimed to investigate the effect of preconception paternal smoking on birth defects in offspring in a prospective population based study. Methods: We carried out a prospective, population-based study utilizing preconception registry data from National Free Preconception Health Examination Project during 2010-12, and a matched case control study (1:1) with birth defects and normal pregnancy by maternal province, supplement of folic acid matched, and paternal alcohol consumption as well. Findings: A total of 566439 couples with complete preconception father smoking behavior were enrolled. Total paternal smoking rate before conception was 28.7% (162482), among whom 8.7% (49303) stopped smoking, 13.3% (75517) decreased and 6.6% (37662) continued in early pregnancy. Logistic regression models were used to examine the association between birth defects and smoking behavior. Paternal continued smoking group (P=0.000, OR=1.868, 95% CI: 1.361-2.564) and pre-conception paternal decreased smoking group in early pregnancy (P=0.007, OR=1.414, 95% CI: 1.100-1.816) were at higher risk of birth defects, while there was no difference with those father quitting smoking compared to paternal never smoking group (P=0.407). In addition, preconception paternal smoking behavior change was associated with birth defects in offspring in matched case control analysis, compared to those fetus whose father continued smoked, the fetus whose father quitted (P=0.003, OR=0.316, 95% CI: 0.149-0.669) or decreased smoking (P=0.000, OR=0.250, 95% CI: 0.129-0.485) were at lower risk of birth defects, especially for congenital heart diseases, limb abnormalities, digestive tract anomalies and neural tube defects. Interpretation: Preconception paternal smoking demonstrated to be associated with birth defects including congenital heart diseases, limb abnormalities and neural tube defects. Preconception paternal smoking cessation should be strengthened for eliminating related birth defects as part of pregnancy education program before pregnancy. Funding Statement: Database reported in this publication was supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. This study was supported by Chinese association of maternal and child health studies. Declaration of Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Zhang SK reports National Free Preconception Health Examination Project (NFPHEP) supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. No other disclosures were reported. Ethics Approval Statement: The Institutional Review Board of Chinese Association of Maternal and Child Health Studies approved the project, and written informed consent was obtained from the participants (IRB201001).

Cigarette smoking significantly alters sperm DNA methylation patterns.

Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre-conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never-smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome-wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome-wide in sperm DNA from men who smoke compared with never-smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre-conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

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.

Ethical aspects of paternal preconception lifestyle modification

This Clinical Opinion points to a potential conflict between the scarcity of evidence on paternal preconception risk factors for adverse pregnancy outcomes and the view that preconception care should be also directed at men. We argue that from an ethical perspective, responsible fatherhood starts already before conception, as long as the evidence increases on the benefits of paternal preconception lifestyle (modification). Our explorative study suggests that the strength of the evidence for paternal preconception lifestyle modification is important for men. We argue that 5 aspects together determine the moral responsibility of prospective fathers to modify their behavior: the strength of the evidence of the risk factor, the modifiability of the risk, the efforts necessary to eliminate or diminish the risk factor, the severity of harm, and the probability that harm will occur and that it will be prevented by modifying the risk factor. The case of paternal preconception smoking illustrates the analysis.

Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood

BackgroundRheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known.ObjectivesTo examine childhood SES measures, SES trajectory and other perinatal factors in...

Abstract 662: Effect of tobacco smoking on the risks of childhood acute lymphocytic and myeloid leukemias, by phenotypic and cytogenetic subtype

Abstract Background: Tobacco smoke contains several myelotropic carcinogens (i.e., benzene, 1,3 butadiene and formaldehyde) and is strongly suspected of damaging pluripotential hematopoietic stem cells. Objective: To examine the role of tobacco smoking in the etiology of childhood acute lymphocytic leukemia (ALL) and myeloid leukemia (AML), defined by phenotypic feature and type of chromosomal aberrations at diagnosis, such as translocation t(12:21) or high hyperdiploidy (51+ chromosomes). Method: Children (0-14 years old) newly diagnosed with ALL (n=839) and AML (n=145) were enrolled in a case-control study in California (1995-2008). Population-based controls (n=1226) were matched to cases on age, sex, Hispanic status, and maternal race. Parents provided information on exposure to tobacco smoking before and after their child's birth. Conventional karyotype and fluorescence in situ hybridization (FISH) data were abstracted from the medical reports. Additional FISH assays using pre-treatment bone marrow specimens were conducted to complete cytogenetic classification. Unconditional logistic regression analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for developing leukemia, using binary variable for ever/never smoked (ORbinary) and continuous variable for number of cigarettes smoked per day (ORcig). All models included the matching factors and household income. Results: In univariate analyses, elevated risks of B-cell ALL (n=722) were associated with pre-conception paternal smoking (“PCPS”) (ORcig= 1.02; 95% CI:1.00-1.03; p=0.04) and child's passive smoking (“CPS”) after birth (ORbinary=1.32; 95% CI:1.21-3.50; p=0.02). Analyses using mutually exclusive exposure variables (i.e., only “PCPS,” only “CPS,” and both “PCPS-CPS,” compared to no smoking) showed that the elevated risk of B-cell ALL was limited to children exposed to both “PCPS-CPS” (OR=1.50, 95% CI:1.10-2.04). The magnitude of this association increased for 133 B-cell ALL cases harboring chromosomal translocation t(12;21) (OR=2.37; 95% CI:1.41-4.01). Weaker associations were seen between “PCPS” and “CPS” and B-cell ALL harboring other chromosome translocations (n=82) or deletions (n=63). Tobacco smoking did not appear to be associated with hyperdiploid B-cell ALL (n=228) and T-cell ALL (n=70). Child's passive smoking conferred a 1.5-fold increased risk of AML (95% CI:0.98-2.26; p=0.06), with a higher risk observed for those with chromosome aberrations linked to a “favorable” prognosis (ORbinary=1.94; p=0.07; n=80). No excess risks were seen with maternal smoking during pregnancy, after accounting for other sources of smoking. Conclusions: Exposure to tobacco smoking is an important predictor of childhood ALL, and possibly AML. The observed risks contrast by phenotypic and cytogenetic subtype, providing insights in the etiology of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 662. doi:1538-7445.AM2012-662

Parental Smoking and the Risk of Childhood Leukemia

Cigarette smoke has been linked to adult myeloid leukemia; however, the association between parental smoking and childhood leukemia remains unclear. Parental smoking and the risk of childhood leukemia were examined in the Northern California Childhood Leukemia Study, a case-control study, between 1995 and 2002. The present analysis included 327 acute childhood leukemia cases (281 acute lymphoblastic leukemia (ALL) and 46 acute myeloid leukemia (AML)) and 416 controls matched on age, sex, maternal race, and Hispanic ethnicity. Maternal smoking was not associated with an increased risk of either ALL or AML. Paternal preconception smoking was significantly associated with an increased risk of AML (odds ratio = 3.84, 95% confidence interval: 1.04, 14.17); an increased risk for ALL was suggestive for paternal preconception smoking (odds ratio = 1.32, 95% confidence interval: 0.86, 2.04). Greater risks of ALL were observed compared with the risk associated with paternal preconception smoking alone, when paternal preconception smoking was combined with maternal postnatal smoking (p(interaction) = 0.004) or postnatal passive smoking exposure (p(interaction) = 0.004). These results strongly suggest that exposure to paternal preconception smoking alone or in combination with postnatal passive smoking may be important in the risk of childhood leukemia.

RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia

We explored the relationship of RAS gene mutations with epidemiologic and cytogenetic factors in a case series of children with leukemia. Diagnostic bone marrow samples from 191 incident leukemia cases from the Northern California Childhood Leukemia Study were typed for NRAS and KRAS codon 12 and 13 mutations. A total of 38 cases (20%) harbored RAS mutations. Among the 142 B-cell acute lymphoblastic leukemia (ALL) cases, RAS mutations were more common among Hispanic children (P=0.11) or children born to mothers <30 years (P=0.007). Those with hyperdiploidy at diagnosis (>50 chromosomes) had the highest rates of RAS mutation (P=0.02). A multivariable model confirmed the significant associations between RAS mutation and both maternal age and hyperdiploidy. Interestingly, smoking of the father in the 3 months prior to pregnancy was reported less frequently among hyperdiploid leukemia patients than among those without hyperdiploidy (P=0.02). The data suggest that RAS and high hyperdiploidy may be cooperative genetic events to produce the leukemia subtype; and furthermore, that maternal age and paternal preconception smoking or other factors associated with these parameters are critical in the etiology of subtypes of childhood leukemia.

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case – control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers.

Paternal Cigarette Smoking and the Risk of Childhood Cancer Among Offspring of Nonsmoking Mothers

Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients (<15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor.

Epidemiology of childhood leukemia.

Leukemia is the most common malignancy among children under the age of 15. It has recently been shown that the incidence rate of acute lymphoblastic leukemia, the predominant type of childhood leukemia in the United States and many European countries, is increasing among young children. Several recent etiologic studies focusing on the investigation of leukemia risk among young children have suggested that maternal exposures during pregnancy, such as low-dose radiation from the Chernobyl accident, parental alcohol consumption, and dietary habits, may be related to the risk of leukemia in infants. Paternal preconception smoking has also been reported to be associated with an increased risk of childhood leukemia, particularly among young children. Other etiologic hypotheses investigated recently include the association of childhood leukemia with infection and with birth weight. This paper briefly surveys the progress of epidemiologic research on childhood leukemia in 1996.