Birth-related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: the ESCALE study (SFCE)

Since neuroblastoma occurs very early in children's lives, it has been hypothesized that pre- and perinatal factors may play a role in its etiology. This study investigated the role of birth characteristics, congenital malformation and maternal reproductive history in neuroblastoma. The data used were generated by the national population-based case-control study, ESCALE, conducted in France in 2003-2004. The mothers of 191 neuroblastoma cases and 1,681 controls, frequency-matched by age and gender, were interviewed by telephone, using a standardized questionnaire, on several factors including pregnancy, medical history, lifestyle, childhood medical conditions and exposures. A positive association between congenital malformation and all neuroblastoma cases was observed [Odds ratio (OR) = 2.2, 95% confidence interval (95% CI): 1.1-4.5]. Congenital malformations were highly associated to neuroblastoma in children aged less than 1 year (OR = 16.8, 95% CI: 3.1-90), while no association was observed in children aged 1 year or more (OR = 1.0, 95% CI: 0.3-2.9). A negative association with a maternal history of spontaneous abortions was also found (OR = 0.6, 95% CI: 0.4-0.9). The results strongly support the hypothesis that congenital anomalies may be associated with neuroblastoma, particularly in infant (less than 1 year of age).     

Parental smoking,maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies

Neuroblastoma (NB) is the most common extra-cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population-based case–control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life-style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta-analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9–1.7]; summary OR from meta-analysis 1.1 [95% CI 1.0–1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9–1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1–2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8–1.4], summary OR from meta-analysis 1.0 [95% CI 0.9–1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy.     

Maternal residential pesticide use during pregnancy and risk of malignant childhood brain tumors: A pooled analysis of the ESCALE and ESTELLE studies (SFCE)

Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population‐based, case–control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency‐matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2–1.8) and, more specifically, with insecticide (OR 1.4, 1.2–1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose–response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT.     

Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE,France)

Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population‐based case‐control studies with similar designs conducted in 2003–2004 and 2010–2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population‐based studies may provide further insight into findings by CBT subtypes.     

Perinatal characteristics and risk of neuroblastoma

Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common infant malignancy. The etiology of NB is largely unknown. We explored the association between birth record variables and subsequent NB development in a population-based case-cohort study in Minnesota by linking the birth and cancer registries. NB cases included 155 children born during 1976-2004 who were diagnosed from 28 days through 14 years of age. The comparison group included 8,752 individuals randomly sampled from the birth cohort of cases. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Controlling for birth year and sex, maternal history of one fetal loss (HR = 1.7, 95% CI 1.2-2.5), maternal prenatal drug-use (recorded starting in 1992) (HR = 5.7, 95% CI 2.3-14) and child's small size for gestational age (HR = 2.1, 95% CI 1.1-4.0) were significantly associated with NB. Age group specific analyses indicated that maternal hypertension (HR = 3.0, 95% CI 1.3-7.2) and maternal age <20 years (HR = 2.6, 95% CI 1.1-6.1) increased risks for infant NB only. Our study provides evidence that a few perinatal exposures as recorded in birth records may play a role in NB etiology.     

Parental smoking,maternal alcohol,coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE,France)

Purpose

To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT.

Methods

We pooled data from two French national population-based case–control studies with similar designs conducted in 2003–2004 and 2010–2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin.

Results

No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74).

Conclusion

We found some evidence of a weak association between paternal smoking in the year before the child’s birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes.

     

Childhood cancer incidence and survival in Japan and England: A population‐based study (1993‐2010)

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).     

Informing etiologic research priorities for squamous cell esophageal cancer in Africa: A review of setting‐specific exposures to known and putative risk factors

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC‐affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.     

HPV‐avertable cancer risks in India: A pooled analysis of 9 observational studies

Recent advances in cancer stem cell biology have shown that cancer stem‐like cells with epithelial–mesenchymal transition (EMT) phenotypes are more aggressive and cause relapse; however, absence of a specific marker to isolate these EMT stem‐like cells hampers research in this direction. Cell surface markers have been identified for isolating cancer stem‐like cells, but none has been identified for isolating cancer stem‐like cells with EMT phenotype. Recently, we discovered that Vimentin, an intracellular EMT tumor cell marker, is present on the surface of colon metastatic tumor nodules in the liver. In our study, we examined the potential of targeting cell surface Vimentin (CSV) to isolate stem‐like cancer cells with EMT phenotype, by using a specific CSV‐binding antibody, 84‐1. Using this antibody, we purified the CSV‐positive, CD133‐negative (csVim⁺CD133⁻) cell population from primary liver tumor cell suspensions and characterized for stem cell properties. The results of sphere assays and staining for the stem cell markers Sox2 and Oct4A demonstrated that csVim⁺CD133⁻ cells have stem‐like properties similar to csVim⁻CD133⁺ population. Our investigation further revealed that the csVim⁺CD133⁻ cells had EMT phenotypes, as evidenced by the presence of Twist and Slug in the nucleus, the absence of EpCAM on the cell surface and basal level of expression of epithelial marker E‐cadherin. The csVimentin‐negative CD133‐positive stem cells do not have any EMT phenotypes. csVim⁺CD133⁻ cells exhibited more aggressively metastatic in livers than csVim⁻CD133⁺ cells. Our findings indicate that csVim⁺CD133⁻ cells are promising targets for treatment and prevention of metastatic hepatocellular carcinoma.     

Age‐specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium

Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in relation to age‐specific risks of EA and EGJA. We pooled individual participant data from eight population‐based, case–control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age‐specific (<50, 50–59, 60–69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack‐years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early‐onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR = 8.06, 95% CI: 4.52, 14.37; p_{effect modification} = 0.01) and BMI (OR_{BMI ≥ 30 vs. <25} = 4.19, 95% CI: 2.23, 7.87; p_{effect modification} = 0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age‐specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers.     

Nasopharyngeal Carcinoma (NPC) Risk Factors: A Systematic Review and Meta-Analysis of the Association with Lifestyle,Diets, Socioeconomic and Sociodemographic in Asian Region

Objective: Risk factors of nasopharyngeal carcinoma (NPC) have been linked with diets, life style and viral infections. NPC is more rampant in Asian populations than non-Asian countries. Our study aims to assess the validity of the suggestions provided by multiple case control studies demonstrating that salted fish consumption, smoking and alcohol consumption are associated with the risk of NPC in Asia. Methods: Search for related literature on salted fish, smoking and alcohol consumption were performed via Science Direct, PubMed databases and Google Scholar. Articles included in this study were from 2009 to 2017, with specific focus on salted fish, smoking and alcohol consumption as risk factors of NPC. This study excluded all articles published prior to 2009 and articles involving other cancers. Data were extracted independently by two different researchers and harmonized. Meta-analysis was conducted on the obtained data, by using R package Meta to create funnel and forest plots. Results: The meta-analysis revealed that salted fish, smoking and alcohol consumption were significantly associated to NPC risk with random effect model score showing OR of 1.41 at 95% confidence interval (CI) of 1.13-1.75 (P<0.01), OR of 1.89 at 95 % CI of 1.49 – 2.38, and OR: 1.42 at 95 % CI of 1.23 – 1.65 respectively. Our results also revealed significant association of salted meat, salted vegetables, house type, wood dust exposure associated with NPC risk with p values less than 0.05. Conclusion: This study proposes that salted fish intake, smoking and alcohol consumption might be linked to NPC risk in Asians. Further studies are necessary to ascertain the molecular mechanisms and clarify if the associated path that could function as therapeutic target.     

Facilitation of school re‐entry and peer acceptance of children with cancer: a review and meta‐analysis of intervention studies

Increased survival rates from childhood cancer call for efforts to reintegrate children with cancer back into their academic and social environments. The aims of this study were to: (1) review and analyse the existing literature on school re‐entry interventions for children with cancer; and (2) discuss the importance of peer involvement in the treatment. Relevant databases were searched using equivalent search algorithms and six studies were selected that target children with cancer and/or their classmates. Two authors independently reviewed the literature for data extraction. The articles were reviewed using the PRISMA model for reporting reviews. Statistical calculations for the meta‐analyses were done using Review Manager 5.2. The meta‐analyses showed significant effects of school re‐entry programmes in terms of enhancing academic achievement in children with cancer (P = 0.008) and lowering their levels of depression (P = 0.05). Increased knowledge among classmates was associated with less fear and a more positive attitude towards the child with cancer. Due to limited numbers of patients, lack of control groups, and the diversity of intervention strategies used in previous studies, there is a need for intervention programmes exploring the optimal path for the reintegration of children with cancer into the education system and into their peer groups.     

Lifecourse socioeconomic status and cancer‐related risk factors: Analysis of the WHO study on global ageing and adult health (SAGE)

Few studies have examined cancer‐related risk factors in relation to SES across the lifecourse in low to middle income countries. This analysis focuses on adult women in India, China, Mexico, Russia and South Africa, and examines the association between individual, parental and lifecourse SES with smoking, alcohol, BMI, nutrition and physical activity. Data on 22,283 women aged 18 years and older were obtained from the 2007 WHO Study on Global Aging and Adult Health (SAGE). Overall, 34% of women had no formal education, 73% had mothers with no formal education and 73% of women had low lifecourse SES. Low SES women were almost four times more likely to exceed alcohol use guidelines (OR: 3.86, 95% CI: 1.23–12.10), and 68% more likely to smoke (OR: 1.68, 95% CI: 1.01–2.80) compared with higher SES. Women with low SES mothers and fathers were more likely to have poor nutrition (Mothers OR: 1.59, 95% CI: 1.17–2.16; Fathers OR: 1.33, 95% CI: 1.11–1.59) and more likely to smoke (Mothers OR: 1.46, 95% CI: 1.15–1.87; Fathers OR: 2.17, 95% CI: 1.80–2.63) compared with those with high SES parents. Women with stable low lifecourse SES were more likely to smoke (OR: 2.55, 95% CI: 1.47–4.43), while those with declining lifecourse SES were more likely to exceed alcohol use guidelines (OR: 3.63, 95% CI: 1.07–12.34). Cancer‐related risk factors varied significantly by lifecourse SES, suggesting that cancer prevention strategies will need to be tailored to specific sub‐groups in order to be most effective.     

A pooled analysis of case-control studies of thyroid cancer. VII. Cruciferous and other vegetables (International)

OBJECTIVE: To investigate the association between cruciferous and other vegetables and thyroid cancer risk we systematically reanalyzed the original data from 11 case–control studies conducted in the US, Asia, and Europe.METHODS: A total of 2241 cases (1784 women, 457 men) and 3716 controls (2744 women, 972 men) were included. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Summary ORs for all studies combined were computed as the weighted average of the estimates from each study.RESULTS: A decreased risk for the highest level of cruciferous vegetable intake, as compared to the lowest, was observed in Los Angeles, Hawaii, Connecticut, southeastern Sweden, Tromsø, and Switzerland; the OR were above unity in Japan and Uppsala, whereas no material association was found in northern Sweden, Italy, or Greece. The OR values for all studies combined were 0.87 (95% CI 0.75–1.01) for moderate and 0.94 (95% CI 0.80–1.10) for high cruciferous vegetables intake. The results were similar in studies from iodine-rich areas and endemic goiter areas, and were consistent when the analysis was restricted to papillary carcinomas and women. The summary OR values for vegetables other than cruciferous were 1.04 (0.88–1.22) for moderate and 0.82 (0.69–0.98) for high consumption.CONCLUSIONS: This combined analysis indicates that cruciferous vegetables are not positively related to thyroid cancer risk. Their effect does not seem to be substantially different from that of other vegetables, which appear to be protective on this cancer.     

Prevalence of high‐risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population—A pooled analysis from three studies

Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community‐based studies to report the high‐risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age‐adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age‐adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high‐risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high‐grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening.     

Global incidence,risk factors and trends of vulvar cancer: A country-based analysis of cancer registries

Vulvar cancer is an uncommon malignancy. Vulvar cancer alarmed the public health problem in terms of the cost of diagnostic and medical treatments and psychical health of females. Our study aims to provide a thorough analysis of the global disease burden, related risk factors and temporal incidence trends of vulvar cancer in population subgroups. Data from Global Cancer Observatory and the Cancer Incidence in Five Continents Plus were used for the vulvar cancer incidence. Age-standardized rates (ASR) were used to depict the incidence of vulvar cancer. The 10-year trend of incidence was assessed using joinpoint regression with average annual percentage change and 95% confidence intervals in various age groups, while its correlations with risk factors were investigated using linear regression. Higher ASR were found in Western Europe (2.4), Northern America (1.9), Northern Europe (1.9), Australia and New Zealand (1.8) and Eastern Africa (1.4). The associated risk factors of higher vulvar cancer incidence were gross domestic product per capita, Human Development Index, higher prevalence of smoking, alcohol drinking, unsafe sex and human immunodeficiency virus infection. The overall trend of vulvar cancer incidence was increasing. An increasing trend was found in older females while a mixed trend was observed in younger females. The disease burden of vulvar cancer follows a bimodal pattern according to its two histologic pathways, affecting women in both developed and developing regions. Smoking cessation, sex education and human papillomavirus vaccination programs should be promoted among the general population. Subsequent studies can be done to explore the reasons behind the increasing trend of vulvar cancer.