Maternal Alcohol Consumption during Pregnancy and Risk of Childhood Leukemia: Systematic Review and Meta-analysis

Latino‐Martel, Paule; Chan, Doris S. M.; Druesne-Pecollo, Nathalie; Barrandon, Émilie; Herçberg, Serge; Norat, Teresa

doi:10.1158/1055-9965.epi-09-1110

Cited by 89 publications

(66 citation statements)

References 60 publications

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“…Results obtained for the effects of maternal use of alcohol during pregnancy and pediatric cancers have been mixed [37][38][39][40]. A meta-analysis of childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) reported significantly increased odds for AML (odds ratio = 1.56) but not for ALL in association with maternal use of alcohol during pregnancy [41]. Two large-scale studies [37,38] assessed the effects of maternal drinking during pregnancy on ALL risk finding that alcohol consumption greater than one drink per day was related to incidence of ALL in offspring [38], though the other study did not find a relationship [37].…”

Section: Discussionmentioning

confidence: 99%

Cross-Generational Effects of Alcohol Dependence in Humans on HRAS and TP53 Methylation in Offspring

et al. 2017

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Aim:We hypothesized that cross-generational effects of alcohol exposure could alter DNA methylation and expression of the HRAS oncogene and TP53 tumor suppressor gene that drive cancer development. Methods: DNA methylation of the HRAS and TP53 genes was tested in samples from young participants (Mean age of 13.4 years). Results: Controlling for both personal use and maternal use of substances during pregnancy, familial alcohol dependence was associated with hypomethylation of CpG sites in the HRAS promoter region and hypermethylation of the TP53 gene. Conclusion: The results suggest that ancestral exposure to alcohol can have enduring effects that impact epigenetic processes such as DNA methylation that controls expression of genes that drive cancer development such as HRAS and TP53. Alcohol use is responsible for about 4% of all deaths worldwide [1]. A portion of this increased incidence of all-cause mortality is due to head and neck cancers, particularly of the pharynx, larynx, oral cavity and esophagus as well as the liver [2]. Alcohol abuse and dependence are frequently seen in individuals diagnosed with Head and Neck Squamous Cell Carcinoma [3]. Moreover, prospective epidemiological data show that alcohol use has a significant dose-response relationship with increased hazard ratios for developing cancer starting at three drinks per day [4]. Consumption of alcohol appears to have a direct effect on gastrointestinal tissue promoting the development of malignancy. The incidence of the head and neck cancers is in direct proportion to the dilution of alcohol in the gut so that mouth cancers are most common followed by esophageal cancers with the least incidence occurring in stomach and intestinal cancers [5].Integrated approaches to understanding cancer risk appear to require analysis of genetic and epigenetic factors along with gene expression profiles to address the complexity of cancer etiology [6]. In addition to the direct effect of alcohol on tissues exposed to alcohol, the potential exists for alcohol to change the methylation of oncogenes and tumor suppressor genes involved in tumor development. Defining the factors that contribute to this increased risk for these cancers is critical to the ultimate goal of reducing cancer development.A diverse set of environmental conditions affect DNA methylation [7][8][9] with the potential for altering gene expression [10]. Alcohol use and smoking can produce altered methylation in humans [11,12]. Cross generational effects have been reported with famine experienced by parents affecting medical conditions and longevity in offspring [13,14]. Although not previously reported in humans, animal studies have shown that ethanol administration can influence DNA methylation through the germline in offspring exposed either through fetal exposure [15] or as a result of paternal exposure [16,17]; changes with the potential to alter every somatic cell in the body across generations. Determining if alcohol consumption in the preconception period in parents influences genes involv...

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Section: Discussionmentioning

confidence: 99%

Cross-Generational Effects of Alcohol Dependence in Humans on HRAS and TP53 Methylation in Offspring

et al. 2017

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“…Alcohol consumption during pregnancy caused a 56% increased risk for childhood AML (Latino-Martel et al (2010). In children born to women who drank during the second or third trimester of pregnancy, odds ratios for leukemia were 10.48 [2.8 -39.1] [Shu et al (1996)].…”

Section: Relative Risk Data Linking Acetaldehyde/alcohol and Leukemiasmentioning

confidence: 99%

Preventing hereditary cancers caused by opportunistic carcinogens

Friedenson¹

2011

Nat Prec

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ObjectivesPrevious studies reported inherited BRCA1/2 deficits can cause cancer by impairing normal protective responses. Opportunistic carcinogens can exploit these deficits by causing chronic inflammation, constant cell death and replacement in a mutagenic environment, DNA crosslinking or double strand breaks. Some of the resulting cancers may be prevented if opportunistic carcinogens are identified. MethodsThe literature was systematically searched for carcinogens capable of exploiting deficits in BRCA1/2 pathways. Search criteria were common exposure, available information, required BRCA1/2 pathway repairs, increased risks for any cancer, and effects on stem cells. ResultsFormaldehyde and acetaldehyde are closely related carcinogens and common pollutants that seem everywhere. Alcohol metabolism also produces acetaldehyde. High levels of either carcinogen overwhelm normal detoxification systems, cause inflammation, inhibit DNA repair and produce DNA cross links as critical carcinogenic lesions. Searching model system studies revealed both carcinogens activate stem cells, BRCA1/2 pathways and connected BRCA1/2 pathways to myeloid leukemia. For example, the BRCA1-BARD1 complex is required for proper nucleophosmin functions. Nucleophosmin prevents a major subset of acute myeloid leukemia (AML). Next, these concepts were independently tested against risks for myeloid leukemia. Epidemiologic results showed that BRCA2 gene defects inherited on both chromosomes increased risks so dramatically that AML occurs in most children. Using data from 14 studies, known/potential heterozygous BRCA1/BRCA2 mutations increased risks for myeloid leukemias by at least 3 fold in 7 studies and by at least 50% in 12.Acetaldehyde occurs in breast milk. In model studies, excessive acetaldehyde/alcohol exposure affects estrogen metabolism and stimulates alternate alcohol detoxification pathways. These pathways can also cause DNA cross linking by releasing oxygen species and activating procarcinogens. Acetaldehyde in rats' drinking water increased incidence of leukemias, lymphomas, pancreatic tumors and fibroadenomas. Six human epidemiologic studies support an association between alcohol related genotype or alcohol consumption and early onset breast cancers, including those in BRCA1/2 mutation carriers. ConclusionsAlthough it is difficult to prove direct causation, BRCA1/2 mutation carriers may reduce cancer risks by avoiding excessive formaldehyde and acetaldehyde. Broader genetic testing and pharmacologic/nutritional detoxification are possible.

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“…exposition foetale a l'alcool et risque de leucemie chez l'enfant (Latino-Martel et al, 2010) ; -ou pour comparer les resultats provenant d'etudes non biaisees a ceux obtenus a partir d'etudes presentant un risque eleve de biais : ex. mortalite dans les essais randomises avec des supplements antioxydants pour la prevention primaire et secondaire (Bjelakovic et al, 2007).…”

Section: Evaluation Du Niveau De Preuveunclassified