Previously, CYP1A1 Ile462Val polymorphism has been indicated to be a risk factor for several malignancies. Increasing reports have focused on the association of CYP1A1 Ile462Val polymorphisms with susceptibility to acute leukemia and have generated controversial results. The goal of the present study was to derive a more precise estimation of the relationship.
Relevant literature has been rigorously searched and screened. Eligible studies were identified for the period up to Apr 2012. Meta-analyses evaluating the association of CYP1A1 Ile462Val variation with acute leukemia were carried out. Subgroup analyses on ethnicity, clinical types and source of controls were further performed.
A total of thirteen publications including fourteen case-control studies with 2164 cases and 4160 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 Ile462Val polymorphism with acute leukemia risk (Val/Val vs Ile/Ile OR = 1.49; 95% CI = 1.11–1.98; dominant model: OR = 1.26; 95% CI = 1.05–1.51; recessive model: OR = 1.38; 95% CI = 1.04–1.83). In subgroup analysis on ethnicity, increased risk was shown among mixed ethnicities (Val/Val vs Ile/Ile: OR = 2.36; 95% CI = 1.46–3.82; dominant model: OR = 1.37; 95% CI = 1.01–1.86; recessive model: OR = 2.20; 95% CI = 1.37–3.53) but not Asians or Caucasians. In subgroup analysis on clinical types, increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (Val/Val vs Ile/Ile: OR = 2.06; 95% CI = 1.42–3.01; recessive model: OR = 1.91; 95% CI = 1.32–2.76) but not in the acute myeloid leukemia (AML) subgroup.
The results of the present study suggest that CYP1A1 Ile462Val polymorphism might be a low-penetrant risk factor for acute leukemia. Subgroup analyses suggest that homozygous Val/Val alleles might modify the susceptibility to ALL.
Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk.
We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures.
We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively.
Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.
Electronic supplementary material
The online version of this article (doi:10.1007/s10552-012-9947-4) contains supplementary material, which is available to authorized users.
Xenobiotic; Chemicals; California; Childhood cancer; Epidemiology
Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL). Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR) of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI): 1.05–1.18, I2 = 18%) during any time period, 1.25 (95% CI: 1.08–1.46, I2 = 53%) preconception; 1.24 (95% CI: 1.07–1.43, I2 = 54%) during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2 = 64%) after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms.
Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.
Histologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.
The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).
These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.
Parental smoking data have been abstracted from the interview records of the case-control study that first indicated that pregnancy radiographs are a cause of childhood cancer (Oxford Survey of Childhood Cancers, deaths from 1953 to 1955). Reported smoking habits for the parents of 1549 children who died from cancer were compared with similar information for the parents of 1549 healthy controls (matched pairs analysis). There was a statistically significant positive trend between paternal daily consumption of tobacco and the risk of childhood cancer (P< 0.001). This association could not be explained by maternal smoking, social class, paternal or maternal age at the birth of the survey child, sibship position or obstetric radiography. About 15% of all childhood cancers in this series could be attributable to paternal smoking.
To evaluate whether candidate genes in innate immunity are associated with childhood leukemia, we conducted an association study with the 1,536 SNPs in 203 genes related to innate immunity.
Incident childhood leukemia cases (n=136) aged from 0 to 18 were recruited from three teaching hospitals in Seoul between 2003 and 2006. Non-cancer controls (n=140) were frequency-matched to cases by age and gender. The information on the characteristics of children and their parents were collected by trained interviewers using structured questionnaire. Candidate genes were selected based on SNP databases (CGAP and SNP500 database), and genotype assay was performed using GoldenGate (Illumina) oligonucleotide pool assay (OPA). False discovery rate (FDR), permutation test, and haplotype analyses were used to identify the SNP with significant association with childhood leukemia. Childhood leukemia risk was estimated as ORs and 95% CIs adjusted for age, gender and birth weight.
Fourteen SNPs in 13 genes (LMAN1, TLR4, STAT4, CCR9, MBP, ZP1, C8B, XDH, C7, C1QG, FGF2, LOC390183, and STAT6) were significantly associated with childhood leukemia risk (FDR p-values <0.05). In particular, LMAN1 rs1127220, TLR4 rs11536897, STAT4 rs13020076, CCR9 rs1471962, and MBP rs10514234 were significant in 5,000 permutation tests (Permutation p-value <0.05). The most significant association with childhood leukemia risk was for the LMAN1 rs1127220 that is in the protein-coding region, this finding was also supported by haplotype analysis.
A number of innate immunity related genes are associated with childhood leukemia, suggesting possible links between the innate immunity system and development of the childhood leukemia.
Childhood Leukemia; Innate Immunity; Single Nucleotide Polymorphism
Polymorphisms in NQO1, a gene coding for the phase II enzyme involved in the detoxification of quinone carcinogens, have been associated with childhood leukemia in some studies, although the observed direction and magnitude of effects have been inconsistent. Therefore, the authors systematically reviewed all published reports describing the effect of NQO1 in de novo childhood leukemia and conducted a meta-analysis of 7 case-control studies that examined the association between NQO1*2 and childhood leukemia. Although a family-based study previously demonstrated overtransmission of this allele among childhood acute lymphoblastic leukemia cases, the meta-analysis showed that the presence of a NQO1*2 variant allele, which reduces the activity of the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), had no significant effect on childhood leukemia. However, there was an increased risk associated with having at least 1 copy of the NQO1*2 allele in a subset of cases with MLL translocations (summary odds ratio = 1.39, 95% confidence interval: 0.98, 1.97). Heterogeneity between studies may be due to differences in population exposures to NQO1 substrates and small sample sizes, as well as potential population stratification in non-family-based studies. Therefore, further research is warranted on the role of NQO1 polymorphisms in the etiology of childhood leukemia, especially among MLL-positive leukemias.
epidemiology; leukemia; meta-analysis; NAD(P)H dehydrogenase (quinone); NQO1; polymorphism, single nucleotide; systematic review
Parental smoking data have been reabstracted from the interview records of the Oxford Survey of Childhood Cancers (deaths from 1971 to 1976). Reported smoking habits for the parents of 2587 children who died with cancer were compared with similar information for the parents of 2587 healthy controls (matched pairs analysis). Maternal daily consumption of cigarettes and paternal use of pipes or cigars were unimportant, but there was a statistically significant positive trend between paternal daily consumption of cigarettes and the risk of childhood cancer (P < 0.001). This association could not be explained by maternal smoking, social class, parental ages at the birth of the survey child, sibship position or obstetric radiography. Relations between maternal consumption of cigarettes and birth weights suggested that (maternal) smoking data were equally reliable for case and control subjects. About 14% of all childhood cancers in this series could be attributable to paternal smoking. These data were combined with smoking data from two previously published reports from the Oxford Survey (deaths from 1953 to 1955, deaths from 1977 to 1981) to obtain further information on risks for different types of cancer and different ages at onset of disease. Paternal cigarette smoking emerged as a potential risk factor both for the generality of childhood cancer and for all ages at onset.
Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer.
We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case–control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4)
No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9–1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9–7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8–2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes.
Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak.
African Americans; breast cancer; cytochrome P4501A1
Evidence indicates that CYP1A1 MspI polymorphism might be a possible risk factor for several malignancies. A growing body of literature has been devoted to the association of CYP1A1 MspI polymorphism with acute myeloid leukemia (AML). However, the results remain conflicting. The aim of the present study was to derive a more precise estimation of the relationship.
Meta-analyses assessing the association of CYP1A1 MspI variation with AML were conducted and subgroup analyses on ethnicity and age groups were further performed. Eligible studies were identified for the period up to May 2012.
A total of ten case–control studies including 1330 cases and 3688 controls were selected for analysis. The overall data failed to indicate a significant association of CYP1A1 MspI polymorphism with AML risk (C vs T: OR = 1.13; 95%CI = 0.87-1.48; CC vs TT: OR = 1.72; 95%CI = 0.99-3.01; CC + TC vs TT: OR = 1.16; 95%CI = 0.86-1.55). In subgroup analysis stratified by ethnicity, significant AML risk was shown among Asians (CC + TC vs TT: OR = 1.33; 95%CI = 1.09-1.62) but not Caucasians or mixed races. In subgroup analysis regarding age groups, no associations were observed in either the childhood AML or the adult AML subgroups.
The results of the present study suggested that CYP1A1 MspI polymorphism might be a risk factor for AML among Asians. Further investigations are needed to confirm the conclusions.
CYP1A1 MspI; Acute myeloid leukemia; Malignancy; Susceptibility; Meta-analysis; Polymorphism
Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a possible risk factor for several cancers. Published studies on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are controversial. This study aimed to determine this relationship accurately.
Meta-analyses that assessed the association of CYP2E1 RsaI/PstI variations with gastric cancer were conducted. Subgroup analyses on ethnicity, smoking status, alcohol consumption, and source of controls were also performed. Eligible studies up to Mar 2012 were identified.
After rigorous searching and screening, 24 case-control studies comprising 3022 cases and 4635 controls were selected for analysis. The overall data failed to indicate the significant associations of CYP2E1 RsaI/PstI polymorphisms with the gastric cancer risk [c2 vs. c1: odds ratio (OR) = 1.06; 95% confidence interval (CI) = 0.88–1.28; c2c2 vs. c1c1: OR = 1.23; 95% CI = 0.78–1.92; c2c2+c1c2 vs. c1c1: OR = 0.93; 95% CI = 0.79–1.10]. Similar results were observed in the subgroup analyses on ethnicity, drinking status, and source of controls. However, in the subgroup analysis on smoking status, a borderline increase in cancer risk was found among long-term smokers (c2c2+c1c2 vs. c1c1: OR = 1.39; 95% CI = 1.00–1.92).
CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to gastric cancer among individuals who have a smoking history. Large and well-designed studies are needed to confirm this conclusion.
CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia.
MATERIALS AND METHODS:
Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia.
The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ2- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL.
The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
Acute leukemia; CYP3A5; drug metabolism; polymorphism
We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.
Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.
Two authors independently abstracted data and assessed the quality of each study.
Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).
Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.
child; leukemia; meta-analysis; occupational exposure; pesticides
Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sex-matched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 exon 7 Ile462Val and CYP1B1 Leu432Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 MspI or CYP1B1 Leu432Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the Ile/Val genotype at CYP1A1 exon 7 locus were at decreased risk of having lung cancer compared to those with the Ile/Ile genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% CI 0.19–0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.
lung cancer; cytochrome p-450 polymorphisms; African Americans; Caucasians; smoking
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).
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).
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.
AIM: To study the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by meta-analysis.
METHODS: A meta-analysis was performed to investigate the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by reviewing the related studies until September 2010. Data were extracted and analyzed. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk.
RESULTS: Thirteen published case-control studies including 5336 cases and 6226 controls were acquired. The pooled OR with 95% CI indicated that CYP1A1 Ile462Val polymorphism was significantly related with colorectal cancer risk (Val/Val vs Ile/Ile: OR = 1.47, 95% CI: 1.16-1.86, P = 0.002; dominant model: OR = 1.33, 95% CI: 1.01-1.75, P = 0.04; recessive model: OR = 1.49, 95% CI: 1.18-1.88, P = 0.0009). Subgroup ethnicity analysis showed that CYP1A1 Ile462Val polymorphism was also significantly related with colorectal cancer risk in Europeans (Ile/Val vs Ile/Ile: OR = 1.22, 95% CI: 1.05-1.42, P = 0.008; dominant model: OR = 1.24, 95% CI: 1.07-1.43, P = 0.004) and Asians (Val/Val vs Ile/Ile: OR = 1.40, 95% CI: 1.07-1.82, P = 0.01; recessive model: OR = 1.46, 95% CI: 1.12-1.89, P = 0.005).
CONCLUSION: CYP1A1 Ile462Val may be an increased risk factor for colorectal cancer.
CYP1A1; Polymorphism; Colorectal cancer; Meta-analysis
The CYP1A1 gene encodes for the enzyme, aryl hydrocarbon hydroxylase, which is involved in the biotransformation of various aromatic tobacco precarcinogens. In the present study, the association between CYP1A1 gene polymorphisms (IVS1-728G > A, Thr461Asn and Ile462Val), and the risk of oral cancer, was examined among 157 patients with oral cancer and 132 age-matched controls, in a south Indian population. The strength of the association between CYP1A1 variants and oral cancer was estimated by logistic regression. It was found that Thr461Asn was not polymorphic. Both IVS1-728G > A and Ile462Val frequencies were consistent with Hardy-Weinberg equilibrium in the control group. There were no significant differences in genotype or haplotype frequencies between controls and cases with oral cancer. Hence, CYP1A1 SNPs can be considered as not being associated with oral cancer at either the genotype or haplotype levels in the population studied.
CYP1A1; haplotypes; allele; oral cancer
Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia.
A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses.
Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83) and bean-curd (OR = 0.55; 95% CI: 0.34–0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea.
Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.
Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk.
A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used.
Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (ORadditive model = 1.501, 95% CI 1.112–2.026, POR = 0.008; ORdominant model = 1.316, 95% CI = 1.104–1.569, POR = 0.002) and Asian subgroup analyses (ORadditive model = 2.338, 95%CI = 1.254–4.359, POR = 0.008; ORdominant model = 2.108, 95%CI = 1.498–2.967, POR = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found.
The meta-analysis results suggested that XRCC1 Arg399Gln polymorphism might be associated with elevated childhood ALL risk among Asian population.
Parental smoking data have been re-abstracted from the interview records of the Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) to test further the hypothesis that paternal cigarette smoking is a risk factor for the generality of childhood cancer. Reported cigarette smoking habits for the parents of 555 children diagnosed with cancer in the period 1980–1983 were compared, in two separate matched pairs analyses, with similar information for the parents of 555 children selected from GP lists (GP controls) and for the parents of 555 hospitalized children (hospital controls). When cases were compared with GP controls there was a statistically significant positive trend (P = 0.02) between the risk of childhood cancer and paternal daily consumption of cigarettes before the pregnancy; there was no significant trend for maternal smoking habit. When cases were compared with hospital controls there was a statistically significant negative trend (P< 0.001) between the risk of childhood cancer and maternal daily consumption of cigarettes before the pregnancy; there was no significant trend for paternal smoking habit. Neither of the significant trends could be explained by adjustment for socioeconomic grouping, ethnic origin or parental age at the birth of the child, or by simultaneous analysis of parental smoking habits. Relations between maternal consumption of cigarettes and birth weights suggested that (maternal) smoking data were equally reliable for case and control subjects, although comparisons with national data suggested that the hospital control parents were unusually heavy smokers. These findings give some support for the hypothesis that paternal cigarette smoking is a potential risk factor for the generality of childhood cancers. © 2001 Cancer Research Campaign http://www. bjcancer.com
childhood cancer; smoking; case-control study
Few studies have examined the association between home use of solvents and paint and the risk of childhood leukemia.
In this case–control study, we examined whether the use of paint and petroleum solvents at home before birth and in early childhood influenced the risk of leukemia in children.
We based our analyses on 550 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloid leukemia (AML), and one or two controls per case individually matched for sex, age, Hispanic status, and race. We conducted further analyses by cytogenetic subtype. We used conditional logistic regression techniques to adjust for income.
ALL risk was significantly associated with paint exposure [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.26–2.15], with a higher risk observed when paint was used postnatally, by a person other than the mother, or frequently. The association was restricted to leukemia with translocations between chromosomes 12 and 21 (OR = 4.16; 95% CI, 1.66–10.4). We found no significant association between solvent use and ALL risk overall (OR = 1.15; 95% CI, 0.87–1.51) or for various cytogenetic subtypes, but we observed a significant association in the 2.0- to 5.9-year age group (OR = 1.55; 95% CI, 1.07–2.25). In contrast, a significant increased risk for AML was associated with solvent (OR = 2.54; 95% CI, 1.19–5.42) but not with paint exposure (OR = 0.64; 95% CI, 0.32–1.25).
The association of ALL risk with paint exposure was strong, consistent with a causal relationship, but further studies are needed to confirm the association of ALL and AML risk with solvent exposure.
case-control study; children; leukemia; paint; petroleum; solvents
Children with Down syndrome (DS) have about a 20-fold increased risk of developing leukemia. Early childhood infections may protect against acute lymphoid leukemia (ALL) in children with and without DS. We examined whether maternal infections and health conditions during pregnancy were associated with acute leukemia in children with DS.
We conducted a case-control study of 158 children with DS and leukemia (including 97 cases with acute lymphoblastic leukemia (ALL) and 61 cases with acute myeloid leukemia (AML)) and 173 children with DS during the period 1997–2002. Maternal interview included information about fourteen maternal conditions during gestation that are likely to induce an inflammatory response. We evaluated their prevalence in cases and controls. Five of these were common enough to allow analyses by leukemia subtype.
Vaginal bleeding was the most frequent (18% cases, 25% controls) and was associated with a reduced risk (Odds Ratio (OR)=0.57; 95% Confidence Interval (CI)=0.33–0.99) for all cases combined. Other variables, while showing a potential trend toward reduced risk had effect estimates which were imprecise and not statistically significant. In contrast, amniocentesis was marginally associated with an increased risk of AML (OR=2.06, 95%CI=0.90–4.69).
Data from this exploratory investigation suggest that some health conditions during pregnancy may be relevant in childhood leukemogenesis. Larger epidemiologic studies and other model systems (animal, clinical studies) may provide a clearer picture of the potential association and mechanisms.
inflammation; Down syndrome; leukemia
The purpose of the study was to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection by-products was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs). We included a subset of cases from a population-based case-control study in a case-only study to estimate the interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and without a given variant regarding their exposure to THMs using unconditional logistic regression. The IOR for a postnatal average of total THM above the 95th percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI), 1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the effect of exposure during pregnancy for an average exposure to total THM at or above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast strongly with those from our case-control analysis, in which we considered the exposure to THMs only in relation with ALL, and observed no increase in risk or very moderate ones. The present preliminary study shows suggestive but imprecise results. We found no similar results in the literature, underscoring the need for other studies as well as the potential usefulness of combining exposure and relevant genetic information in such studies.
Background: Cigarette smoking has been associated with acute myeloid leukemia (AML) but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia remains unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (<2 year) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999–2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children (193 acute lymphoid leukemia – ALL, 59 AML and 423 controls), being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR) on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery) and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy). Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% CI 1.40–19.95) for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% CI 1.33–45.5). No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and EAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.
smoking; pregnancy; childhood cancer; infant leukemia; lactation
Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain.
The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth.
A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05–1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes.
Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.
childhood cancer; childhood leukaemia; epidemiology; paternal occupation; social class