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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 (P(trend)=0.06 and 0.02, respectively) and the number of smokers in the home during the child's life (P(trend)=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 (P(interaction)=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.

SUBMITTER: Lee KM

PROVIDER: S-EPMC2787091 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk.

Lee Kyoung-Mu KM Ward Mary H MH Han Sohee S Ahn Hyo Seop HS Kang Hyoung Jin HJ Choi Hyung Soo HS Shin Hee Young HY Koo Hong-Hoe HH Seo Jong-Jin JJ Choi Ji-Eun JE Ahn Yoon-Ok YO Kang Daehee D

Leukemia research 20080808 2

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-ma ...[more]

PMID: 18691756

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Project description:BackgroundCYP1A1 gene polymorphisms and tobacco smoking are among several risk factors for various types of cancers, but their influence on breast cancer remains controversial. We analyzed the possible association of CYP1A1 gene polymorphisms and tobacco smoking-related breast cancer in women from Iraq.Materials and methodsIn this case-control study, gene polymorphism of CYP1A1 gene (CYP1A1m1, T6235C and CYP1A1m2, A4889G) of 199 histologically verified breast cancer patients' and 160 cancer-free control women's specimens were performed by using PCR-based restriction fragment length polymorphism.ResultsThree genotype frequencies (TT, TC, and CC) of CYP1A1m1T/C appeared in 16.1, 29.6, and 54.3% of women with breast cancer, respectively, compared with 41.2, 40, and 18.8% in the control group, respectively. CYP1A1m1 CC genotype and C allele were significantly associated with increased risks for breast cancer in patients (54.3 and 69%, respectively) compared with controls (18.8 and 39%, respectively). While the three genotype frequencies (AA, AG, and GG) of CYP1A1m2A/G were detected in 20.1, 31.2, and 48.7% in patients compared with 46.3, 40.6, and 13.1% in controls, respectively. The frequency of GG genotypes and G allele was significantly higher in patients (48.7 and 64%, respectively) than in the controls (13.1 and 33%, respectively). Smoking women having either CC or GG genotypes showed a highly significant association with increased risk of breast cancer [odds ratio (OR) = 1.607, 95% confidence interval (CI) 0.91-1.64, p = 0.0001, and OR, 1.841, 95% CI, 0.88-1.67, p = 0.0001, respectively]. On the other hand, the T and A alleles of predominantly seen in healthy smoking women (83 and 85%, p = 0.0001, respectively).ConclusionThese findings indicated that both C and G alleles of CYP1A1m1 and m2 were significantly associated with elevated risk of breast cancer in Iraqi women, while the T and A alleles were predominantly seen in healthy controls which may indicate their protective role. The C and G association with breast cancer incidence was more prevalent among tobacco smoking patients. These polymorphisms may be used as biomarkers of breast cancer in women from Iraq.

Dataset Information

Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk.

Publications

Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk.

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