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2.
Am J Gastroenterol ; 115(12): 2007-2016, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32858564

RESUMO

INTRODUCTION: In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC. METHODS: This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC. RESULTS: Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes. DISCUSSION: Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.

3.
Cancer Res ; 80(20): 4578-4590, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32816852

RESUMO

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (P trend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

4.
Nat Commun ; 11(1): 3644, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686686

RESUMO

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.


Assuntos
Neoplasias Colorretais/genética , Proteínas de Neoplasias/genética , Neoplasias do Colo/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Mutação , Prognóstico , Proteína Supressora de Tumor p53/genética
5.
Clin Transl Gastroenterol ; 11(4): e00169, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32352678

RESUMO

INTRODUCTION: Colonoscopy is an imperfect gold standard for detecting colorectal neoplasms because some proportion of adenomas may be missed, mainly small lesions. This proportion is expected to be higher in case of inadequate bowel cleansing, which is frequently seen in routine practice. We estimated the proportions of neoplasms that are in principle detectable by colonoscopy but might be missed in case of incomplete bowel preparation. METHODS: For 8,193 participants of screening colonoscopy in South-Western Germany, recruited between 2005 and 2016, the prevalence and numbers of different findings were extracted from colonoscopy reports and compared according to the reported bowel preparation quality. RESULTS: Bowel preparation quality was reported as good, poor, or was unspecified in 30.3%, 11.1%, and 58.6% of colonoscopy records. Reported prevalences of nonadvanced adenomas (NAAs) were similar among participants with poor and unspecified bowel preparation quality but substantially lower than among participants with good bowel preparation (adjusted prevalence rate ratio [RR] 0.86, 95% confidence interval [CI]: 0.77-0.96). The differences were observed for proximal but not for distal NAAs (RRs 0.82, 95% CI: 0.71-0.95 and 0.95, 95% CI: 0.82-1.10). DISCUSSION: Our study suggests that a significant proportion of NAAs located in the proximal colon might be missed during colonoscopy if bowel cleansing is not adequate. Major efforts should be made to further facilitate and enhance high-quality bowel preparation in routine screening practice.

6.
Br J Cancer ; 122(11): 1604-1610, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32225169

RESUMO

BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. METHODS: This population-based case-control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. RESULTS: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86-4.18) compared to MSS (OR = 1.41, 1.14-1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41-4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24-1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36-2.13) compared to KRAS-mut (OR = 1.26, 0.95-1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40-2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22-1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27-4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16-1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77-1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. CONCLUSIONS: In this large case-control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.

7.
Int J Cancer ; 147(4): 1018-1026, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31943160

RESUMO

Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population-based case-control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50-0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/>71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17-0.76), BRAF mutation (OR = 0.40, 95% CI 0.30-0.83) and CIMP-high (OR = 0.40, 95% CI 0.21-0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20-1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention.

8.
Am J Clin Nutr ; 111(3): 562-569, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31897467

RESUMO

BACKGROUND: Observational studies have consistently shown that a high BMI is associated with increased risk of colorectal cancer (CRC). However, the underlying mechanisms linking obesity to CRC remain unclear. OBJECTIVES: To investigate the associations of BMI and CRC by major molecular pathological subtypes of CRC. METHODS: This analysis included 2407 cases and 2454 controls from a large German population-based case-control study. Information on recent weight and height as well as other demographic and lifestyle data were obtained by standardized interviews. Multinomial logistic regression was used to estimate ORs and 95% CIs for the associations between BMI and risk of CRC by major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype (CIMP), B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. RESULTS: Among women, a higher BMI was differentially and more strongly associated with risk of MSI CRC (OR per 5 kg/m2: 1.69; 95% CI: 1.34, 2.12; Pheterogeneity ≤ 0.001), CIMP-high CRC (OR per 5 kg/m2: 1.57; 95% CI: 1.30, 1.89; Pheterogeneity ≤ 0.001), BRAF-mutated CRC (OR per 5 kg/m2: 1.56; 95% CI: 1.22, 1.99; Pheterogeneity = 0.04), and KRAS-wildtype CRC (OR per 5 kg/m2: 1.35; 95% CI: 1.17, 1.54; Pheterogeneity = 0.01), compared with the risk of CRC in subjects with the molecular feature counterpart. In men, no meaningful differences in CRC risk were observed for the investigated molecular feature pairs. For the association of BMI with MSI CRC, we observed effect modification by sex (Pinteraction = 0.04). Also, in women, the risk of CRC with the serrated pathway features was more strongly increased with higher BMI than risk of CRC with the traditional pathway features (OR per 5 kg/m2: 1.73; 95% CI: 1.28, 2.34; Pheterogeneity = 0.01). CONCLUSIONS: In women, the relation between BMI and MSI-high CRC seems to be stronger than that between BMI and microsatellite-stable CRC. However, a validation in an independent cohort is needed. This observational study was registered at the German Clinical Trials Register (http://www.drks.de; study ID: DRKS00011793), an approved primary register in the WHO network.


Assuntos
Índice de Massa Corporal , Neoplasias Colorretais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/fisiopatologia , Ilhas de CpG , Metilação de DNA , Feminino , Alemanha , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto Jovem
9.
Clin Transl Gastroenterol ; 11(12): e00268, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33512803

RESUMO

Colorectal cancer (CRC) is a leading cause of morbidity and mortality. Post-CRC resection complications and lower quality of life (QoL) are associated with a lower long-term survival. Perioperative administration of probiotics/synbiotics might lower prevalence of side effects and improve QoL and survival among CRC patients. Medline, Web of Science, Cochrane database, Embase, and clinical trials registries were searched in January 2020. Altogether, 16 randomized placebo-controlled probiotic/synbiotic clinical trials that included patients undergoing CRC surgery and investigated postoperative complications and QoL side effects were found. Meta-analyses using random-effects model were performed on data from 11 studies to calculate the effects of probiotics/synbiotics on common CRC resection postoperative side effects and complications. Perioperative probiotics/synbiotics administration was associated with lower infection incidence (odds ratio [OR] = 0.34, P < 0.001), lower diarrheal incidence (OR = 0.38, P < 0.001), faster return to normal gut function (mean difference [MD] -0.66 days, P < 0.001), shorter postoperative antibiotics use (MD -0.64 days, P < 0.001), lower incidence of septicemia (OR = 0.31, P < 0.001), and shorter length of hospital stay (MD -0.41 days, P = 0.110). The results support the hypothesis that short-term perioperative administration of probiotics/synbiotics, which are easy to administer, have few side-effects, and are low cost compared with alternatives, might help to alleviate gastrointestinal symptoms and postoperative complications among CRC patients.

10.
Cancers (Basel) ; 11(3)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901946

RESUMO

Fecal immunochemical tests (FITs) for hemoglobin (Hb) are increasingly used for colorectal cancer (CRC) screening. Most FIT manufacturers instruct that fecal samples from multiple parts of one bowel movement should be obtained. Our aim was to compare the FIT diagnostic performance based on fecal samples from just one versus two different sites of one bowel movement. A total of 1141 participants of screening colonoscopy provided two fecal samples from two different sites of a single bowel movement for FIT analyses. There was no statistically significant difference in the diagnostic performance of the FIT when either one or both fecal samples were used for analysis, with area under the curve (AUC) for detecting CRC ranging from 0.94 (95% confidence interval (CI) 0.84⁻0.99) for one FIT to 0.95 (95%CI 0.86⁻0.99) for a geometric mean of two FITs. The manufacturers' recommendation of sampling multiple sites of the stool aims to reduce intra-individual Hb variability and improve diagnostic performance. If no such improvement can be achieved, the recommendation for multiple-site sampling might have potential adverse effects on population adherence to FIT-based CRC screening. Our results point to a potential of increasing adherence to FIT screening by simplifying instructions for fecal sampling at no loss of the diagnostic performance.

11.
J Natl Cancer Inst ; 111(5): 475-483, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388256

RESUMO

BACKGROUND: Regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for a longer period has been inversely associated with colorectal cancer (CRC) risk. However, CRC is a heterogenic disease, and little is known regarding the associations with molecular pathological subtypes. METHODS: Analyses included 2444 cases with a first diagnosis of CRC and 3130 healthy controls from a German population-based case control study. Tumor tissue samples were analyzed for major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype, B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. Information on past and current use of NSAIDs, including aspirin, was obtained by standardized interviews. Multinomial logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Regular use of NSAIDs was associated with a reduced CRC risk if tumors were MSS (OR = 0.66, 95% CI = 0.57 to 0.77), BRAF wildtype (OR = 0.67, 95% CI = 0.58 to 0.78), or KRAS wildtype (OR = 0.68, 95% CI = 0.58 to 0.80). Regular NSAID use was less clearly and mostly not statistically significantly associated with CRC risk reduction for MSI-high, BRAF-mutated, or KRAS-mutated CRC. In more specific analyses on MSI-high CRC, regular use of NSAIDs was associated with much stronger risk reduction in the absence of BRAF or KRAS mutations (OR = 0.34, 95% CI = 0.18 to 0.65) but not with KRAS- or BRAF-mutated MSI-high CRC (Pheterogeneity < .001). Results for just aspirin use were similar. CONCLUSION: Our study suggests variation in risk reduction of CRC subtypes following regular use of NSAIDs and aspirin. Regular use of NSAIDs and aspirin may be more strongly associated with risk reduction of MSI-high CRC without KRAS or BRAF mutation.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Intervalos de Confiança , Ilhas de CpG/genética , Metilação de DNA/genética , Feminino , Alemanha , Humanos , Modelos Logísticos , Masculino , Instabilidade de Microssatélites , Mutação , Razão de Chances , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Sensibilidade e Especificidade , Fatores de Tempo
12.
Int J Cancer ; 144(10): 2419-2427, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30411799

RESUMO

In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. Our study aims to identify factors associated with apparently false-positive results of FITs. In this cross-sectional study within the German population-based screening colonoscopy program, participants were invited to provide a stool sample for FIT prior to colonoscopy. Four thousand six hundred and fifty six participants aged 50-79 years with no known history of CRC or inflammatory bowel disease (IBD) and no findings of neoplasms at screening colonoscopy were included in the current analyses. Main outcome measures were rates and factors associated with apparently false-positive FIT results. Apparently false-positive FIT results were found for 378 participants (8.1%). Male sex (OR = 1.30, 95%CI 1.03, 1.62), age ≥65 years (OR = 1.27, 95%CI 1.01, 1.59), a BMI ≥30 kg/m2 (OR = 1.81, 95%CI 1.36, 2.40), current smoking (OR = 1.63, 95%CI 1.18, 2.25), use of aspirin (OR = 1.36, 95%CI 1.02, 1.82) and a new diagnosis of IBD (OR = 9.13, 95%CI 2.18, 38.19) or other non-neoplastic findings (OR = 1.86, 95%CI 1.37, 2.51) at screening colonoscopy were independently associated with significantly increased odds of a positive FIT. Although considered false positive in the context of CRC screening, the identified factors associated with apparently false-positive FIT results are known risk factors for and may point to conditions other than colorectal neoplasms that may be potential sources of gastrointestinal bleeding, potentially requiring further medical follow up.


Assuntos
Neoplasias Colorretais/diagnóstico , Idoso , Colonoscopia/métodos , Estudos Transversais , Detecção Precoce de Câncer/métodos , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Gut Microbes ; 9(4): 293-307, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29543545

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Dysbiosis in the gut microbiota may be associated with CRC. This systematic review focuses on differences in gut microbial community between people diagnosed with CRC or adenoma and healthy individuals using fecal samples, emphasizing non-invasive fecal microbiome models for CRC early diagnosis. Nineteen studies were identified in a systematic literature search of Pubmed, Web of Science and ScienceDirect. Several bacteria were reported to differ in abundance between CRC and adenoma cases and healthy controls, with Fusobacterium the most common. Fecal multi-bacterial predictive models used to distinguish CRC patients from healthy controls had reported areas under the receiver operating curve (AUCs) in external validation populations of 0.68-0.77. Though advanced sequencing techniques could in the future complement current non-invasive methods for CRC early detection, more studies with high statistical power, comparable and reproducible methods and external validation of predictive models are needed.


Assuntos
Bactérias/isolamento & purificação , Neoplasias Colorretais/diagnóstico , Fezes/microbiologia , Microbioma Gastrointestinal , Animais , Bactérias/classificação , Bactérias/genética , Neoplasias Colorretais/microbiologia , Humanos
15.
Carcinogenesis ; 38(8): 781-788, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28582482

RESUMO

Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development.


Assuntos
Neoplasias Colorretais/microbiologia , Fusobacterium/isolamento & purificação , Microbioma Gastrointestinal/genética , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Fezes/microbiologia , Feminino , Fusobacterium/genética , Fusobacterium/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
17.
JAMA Pediatr ; 169(8): 791, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26237462
18.
JAMA Pediatr ; 169(6): e151025, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26030516

RESUMO

IMPORTANCE: Childhood cancer is a leading cause of mortality among children and adolescents in the developed world and the incidence increases by 0.9% each year. Leukemia accounts for about 30% of all childhood cancer but its etiology is still mostly unknown. OBJECTIVE: To conduct a meta-analysis of available scientific evidence on the association between breastfeeding and childhood leukemia. DATA SOURCES: A thorough search for articles published between January 1960 and December 2014 researching the association between breastfeeding and childhood leukemia was conducted on PubMed, the Cochrane Library, and Scopus (performed in July and December 2014), supplemented by manual searches of reference lists. STUDY SELECTION: To be included in the meta-analyses, studies had to be case control; include breastfeeding as a measured exposure and leukemia as a measured outcome; include data on breastfeeding duration in months; and be published in a peer-reviewed journal with full text available in English. DATA EXTRACTION AND SYNTHESIS: The search identified 25 relevant studies, 18 of which met all inclusion criteria. No publication bias or heterogeneity among these 18 studies were detected. The quality of each study that met the inclusion criteria was assessed using the Newcastle-Ottawa Scale. Multiple meta-analyses were conducted using the random effect model on raw data in the StatsDirect statistical program. MAIN OUTCOMES AND MEASURES: No or short duration of breastfeeding and the incidence of childhood leukemia. RESULTS: The meta-analysis of all 18 studies indicated that compared with no or shorter breastfeeding, any breastfeeding for 6 months or longer was associated with a 19% lower risk for childhood leukemia (odds ratio, 0.81; 95% CI, 0.73-0.89). A separate meta-analysis of 15 studies indicated that ever breastfed compared with never breastfed was associated with an 11% lower risk for childhood leukemia (odds ratio, 0.89; 95% CI, 0.84-0.94), although the definition of never breastfed differed between studies. All meta-analyses of subgroups of the 18 studies showed similar associations. Based on current meta-analyses results, 14% to 19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. CONCLUSIONS AND RELEVANCE: Breastfeeding is a highly accessible, low-cost public health measure. This meta-analysis that included studies not featured in previous meta-analyses on the subject indicates that promoting breastfeeding for 6 months or more may help lower childhood leukemia incidence, in addition to its other health benefits for children and mothers.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Leucemia/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Humanos , Incidência , Leucemia/prevenção & controle , Razão de Chances , Risco , Estatística como Assunto
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