Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk

Abstract

We conducted a case–control study to evaluate the association between paternal smoking and childhood leukemia and to evaluate potential modification by polymorphisms in CYP1A1. Histologically confirmed childhood leukemia cases (n = 164) and non-cancer controls (n = 164) were recruited from three teaching hospitals in Seoul, Korea. Five single nucleotide polymorphisms in CYP1A1 (–17961T>C, –9893G>A, I462V, 1188C>T (*2A), and 11599C>G) were genotyped and haplotypes were estimated by the expectation-maximization method. We also conducted a meta-analysis of 12 studies that have reported the association between paternal smoking and childhood leukemia risk. Paternal smoking at home was associated with all leukemias (OR = 1.8, 95% CI = 1.1–2.8) and acute lymphoblastic leukemia (ALL) (2.0, 1.2–3.4). An increasing trend in risk was observed for pack-years smoked after birth (Ptrend = 0.06 and 0.02, respectively) and the number of smokers in the home during the child's life (Ptrend = 0.05 and 0.03, respectively). Among those without the CGACC haplotype, ALL risk was significantly increased by the father's smoking at home (2.8, 1.5–5.3) and the presence of at least one smoker in the home (2.3, 1.2–4.4), and the test for interaction was significant (Pinteraction = 0.03 and 0.02, respectively). The meta-analysis showed that overall paternal smoking (1.13, 1.04–1.24) and smoking before the pregnancy of the child (1.12, 1.04–1.21) were significantly associated with childhood leukemia risk. Our results suggest that paternal smoking is a risk factor for childhood leukemia and the effect may be modified by CYP1A1 genotype.

Whither must spermatozoa wander? The future of laboratory seminology

“…Such an explanation might also account for the wide range of polygenic neurological disorders (epilepsy, bipolar disease, spontaneous schizophrenia, autism) that occur in children and that are correlated with paternal age at the moment of conception [5,6,[30][31][32]. This model might also explain the childhood cancer associated with DNA damage induced in spermatozoa by the fathers' heavy smoking [33,34]. In light of these considerations, detailed examination of DNA damage in human spermatozoa would certainly be an important objective for future versions of the WHO manual.…”

Secondhand Tobacco Smoke

“…0-10, 11-20, 20+) and, when data were available, some assessed continuous consumption of cigarettes per day. One study reported exposure in pack-years (Lee et al, 2009). The SEARC international case-control study assessed polycyclic aromatic hydrocarbons (PAHs) as the main exposure of interest and obtained information on both tobacco smoke and occupational exposures (Cordier et al, 2004).…”

“…iarc.fr/ENG/Monographs/vol100E/100E-02-Table2.23.pdf), and one meta-analysis (Lee et al, 2009) (Table 2.24 available at http://monographs. iarc.fr/ENG/Monographs/vol100E/100E-02-Table2.24.pdf) have evaluated the association of parental tobacco smoking with the risk for lymphatic and haematopoietic cancers.…”

“…Lee et al (2009) performed a meta-analysis of twelve studies on paternal smoking and risk of childhood leukaemia. Paternal smoking before conception of the index child was significantly associated with the risk for acute leukaemia (AL) and acute lymphoblastic leukaemia (ALL) (Fig.…”

“…2.2 Meta-analysis of the association between paternal smoking and childhood leukaemia not with paternal smoking, before and during pregnancy. Lee et al (2009) in Seoul, Republic of Korea, reported that paternal smoking was associated with a significantly increased risk of acute leukaemia and acute lymphoblastic leukaemia in a dose-response manner. The proportion of mothers who smoked was too low (6.1% in controls) to analyse risk in association with maternal smoking.…”