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Previous studies have associated maternal diet during pregnancy with the development of sporadic unilateral retinoblastoma (RB), but few studies have focused on the role of individual nutrients. The aim of this study is to investigate the association between maternal nutrient intake during pregnancy and the development of sporadic unilateral RB in the offspring. A modified food frequency questionnaire, with additional questions on supplement use, was completed via a phone interview. Cases were recruited from hospitals and controls were comprised of friends and relatives of the patient without a history of cancer. Overall, 168 sporadic unilateral RB cases and 145 controls were included in case-control study. We performed logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for child's age, child's sex, parental race/ethnicity, maternal education, total calorie intake during pregnancy, maternal age at birth, maternal smoking during pregnancy, pre-pregnancy body mass index, maternal weight gain during pregnancy, paternal age at birth, and maternal multivitamin use in the year before pregnancy. In the adjusted model, the interquartile (IQR) increase in vitamin A intake, which was measured in retinol activity equivalent (RAE; OR: 0.64, 95 % CI: 0.46-0.90), and vitamin D intake (OR: 0.62, 95 % CI: 0.42-0.91) significantly reduced the risk of sporadic unilateral RB. These findings suggest that a higher intake of vitamins A and D can be a protective factor for sporadic unilateral RB. Further analyses in consideration of multi-exposures such as parental occupational exposures are warranted to discover the complex etiology of sporadic unilateral RB. In addition, the role of nutritional epigenetics for how maternal nutrient intake influences the risk of sporadic unilateral RB in the offspring still needs to be explored., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Prior ecologic studies suggest that UV exposure through sunlight to the retina might contribute to increased retinoblastoma incidence., Aims: Our study objectives were (1) to examine the relationship between exposure to sunlight during postnatal retinal development (prior to diagnosis of sporadic disease) and the risk of retinoblastoma, and (2) to examine the relationship between sun exposure during postnatal retinal development, and the extent of disease among children with unilateral and bilateral retinoblastoma., Methods and Results: We interviewed 511 mothers in the EpiRbMx case-control study about their child's exposure to sunlight during postnatal retinal cell division by examining three time periods prior to Rtb diagnosis coinciding with developmental stages in which outdoor activities vary. Weekly sun exposure was compared by age period, between unilateral (n = 259), bilateral (n = 120), and control (n = 132) children, accounting for two factors affecting UV exposure: residential elevation and reported use of coverings to shield eyes. For cases, association between sunlight exposure and clinical stage was examined by laterality at each age period. After adjusting for maternal education and elevation, sun exposure was lower in cases than controls in all three age periods especially during the first 6 months, and in children 12-23 months whose mothers did not cover their eyes when outdoors. In children diagnosed after 12 months of age, sun exposure during the second year of life (age 12-23 months) appeared inversely correlated (r = -0.25) with more advanced intraocular disease in bilateral Rtb children after adjusting for maternal education, residential elevation, and age of diagnosis (p < .09) consistent with effects of Vitamin D exposure on intraocular spread in earlier transgenic murine models of retinoblastoma, and suggesting potential chemopreventive strategies., Conclusion: Sun exposure in early childhood is protective for retinoblastoma and may decrease degree of intraocular spread in children with bilateral Rtb., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among offspring., Methods: Our population-based case-control study linked data from four nationwide Danish registries and included all cases of retinoblastoma diagnosed in Danish children (<5 y, n = 144) between 1975 and 2014. We focused on two biologically relevant time periods: 90 days preconception to conception for fathers; conception to birth for mothers. Parents were grouped into major industry headings created from Danish industry codes., Results: We observed increased risk of all retinoblastoma for children of fathers in the food and drink industry and iron and metal industry. Bilateral disease was associated with paternal work in manufacturing and land transportation., Conclusion: Our results suggest that some occupational exposures may increase the risk of childhood sporadic retinoblastoma., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Background: While there is evidence that parental exposure to medical radiation is associated with increased risk of sporadic bilateral retinoblastoma in offspring, this association has not been confirmed. Additionally, the relationship between paternal and maternal exposures and sporadic unilateral retinoblastoma has not been fully investigated., Procedure: Data were obtained from two large multicenter case-control studies of retinoblastoma. For the paternal analyses, 268 bilateral cases, 155 unilateral cases, and 358 controls were included. For the maternal analyses, 298 bilateral cases, 184 unilateral cases, and 404 controls were included. Logistical regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) to evaluate the associations between parental exposures to medical radiation and sporadic retinoblastoma, while adjusting for potential confounders., Results: Paternal exposure to medical radiation was not significantly associated with sporadic bilateral retinoblastoma in offspring. However, increasing paternal exposure to gonadal radiation was associated with increased risk of unilateral retinoblastoma (P-trend = .03). Maternal history of upper and lower gastrointestinal (GI) series was associated with bilateral retinoblastoma (OR = 1.9, 95% CI: 1.1-3.2 and OR = 6.9, 95% CI: 2.9-16.4, respectively). However, there was no association between maternal exposure to medical radiation and unilateral retinoblastoma in offspring., Conclusion: Our investigation adds to the evidence that medical radiation exposure in fathers as well as mothers prior to pregnancy may increase the risk of germline alterations leading to the development of retinoblastoma in their offspring. However, our findings could point to a more complex etiological framework for this important pediatric malignancy., (© 2020 Wiley Periodicals LLC.)

Retinoblastoma (RB) is the most common intraocular malignancy. The tumor propagation of RB is maintained by several core transcriptional regulators, including c-Myc. Strictly regulated posttranslational modifications control the c-Myc protein. However, the posttranslational regulatory mechanisms for c-Myc in retinoblastoma remain largely unclear. Here, we identified the zinc-finger protein ZCCHC2 as a critical negative regulator of c-Myc-associated tumorigenesis. Knockout of ZCCHC2 promoted retinoblastoma cell proliferation, whereas ZCCHC2 overexpression had the opposite effect. Meanwhile, the level of ZCCHC2 was positively correlated with retinoblastoma tumorigenesis and animal survival in vivo. Mechanistically, ZCCHC2 was associated with c-Myc and negatively regulated the K63-linked polyubiquitination of c-Myc. We demonstrated that ZCCHC2 inhibits the interaction of the E3 ubiquitin ligase HectH9 with c-Myc and that ZCCHC2 inhibits HectH9-mediated K63-linked polyubiquitination and activation of c-Myc. Altogether, these data suggest that ZCCHC2 plays a role in the regulation of RB tumorigenesis through the inhibition activity of c-Myc., (Copyright © 2019. Published by Elsevier Inc.)

Background: Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood., Methods: Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population., Results: Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15-29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients., Conclusion: Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past., (Published by Oxford University Press 2019.)

As all the structures of the human eye are characterized by sex hormone receptors, this study tested the hypothesis that assisted reproductive technology (ART) treatment influences visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment. A systematic literature search of all original articles published up to August 2018 was performed using the PubMed database, including all original studies available in the literature. Review articles, studies in which participants underwent mixed interventions (i.e. other than ART treatment), studies reporting data on ocular malformations in ART offspring, and studies written in languages other than English were excluded. All selected articles were analysed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Although sparse data suggest that ART treatment can influence visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment, the available evidence is inconclusive given its low level and quality. More high-quality research is needed to assess the potential interaction between ART treatment and the eye., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition., Method: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years., Results: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years., Conclusions: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: MicroRNAs have caught more attention for their role in tumor progression. Retinoblastoma (RB) is one of these ordinary malignant tumors. This study aims to identify whether mir-138-5p can regulate the development of RB, and find out its potential mechanism., Materials and Methods: Mir-138-5p expression in RB cells was monitored by RT-qPCR. Besides, the role of mir-138-5p in RB development was explored through function experiments in vitro. The potential mechanism was further explored by RT-qPCR, luciferase assay, and Western blot assay., Results: In our investigation, mir-138-5p was lower-expressed in RB cells than that in retinal pigment epithelial cells. Moreover, overexpression of mir-138-5p repressed cell viability, migration and invasion, and induced apoptosis of RB cells, while downregulated mir-138-5p increased cell viability, migration and invasion, and reduced apoptosis of RB cells. Furthermore, pyruvate dehydrogenase kinase 1 (PDK1) could be downregulated via overexpression of mir-138-5p, while PDK1 was upregulated via knockdown of mir-138-5p., Conclusions: Our results suggested that mir-138-5p could repress the development of RB via suppressing PDK1, which may offer a new vision for interpreting the mechanism of RB tumorigenesis.

Deletion of the long arm of chromosome 13 (13q deletion syndrome) is very rare chromosomal aberration which causes mental retardation and multiple congenital malformations. Furthermore, it is associated with the increased risk of retinoblastoma. The aim of the paper was to present two cases of retinoblastomna in children with 13q deletion syndrome, discussing the diagnostic and therapeutic management, clinical manifestation and the importance of genetic testing which helps to determine the type of retinoblastoma and may also contribute to the diagnosis of other congenital abnormalities associated with intraocular tumors.

Background: Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma., Methods: Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma., Findings: Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption., Conclusion: The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.

Purpose: Retinoblastoma (RB) is a common pediatric cancer. The study aimed to uncover the mechanisms of RB progression and identify novel therapeutic biomarkers., Methods: The miRNA expression profile GSE7072, which includes three RB samples and three healthy retina samples, was used. After data normalization using the preprocessCore package, differentially expressed miRNAs (DE-miRs) were selected by the limma package. The targets of the DE-miRs were predicted based on two databases, followed by construction of the miRNA-target network. Pathway enrichment analysis was conducted for the targets of the DE-miRNAs using DAVID. The CTD database was used to predict RB-related genes, followed by clustering analysis using the pvclust package. The correlation network of DE-miRs was established. MiRNA expression was validated in another data set, GSE41321., Results: In total, 24 DE-miRs were identified whose targets were correlated with the cell cycle pathway. Among them, hsa-miR-373, hsa-miR-125b, and hsa-miR-181a were highlighted in the miRNA-target regulatory network; 14 DE-miRs, including hsa-miR-373, hsa-miR-125b, hsa-miR-18a, hsa-miR-25, hsa-miR-20a, and hsa-let-7 (a, b, c), were shown to distinguish RB from healthy tissue. In addition, hsa-miR-25, hsa-miR-18a, and hsa-miR-20a shared the common target BCL2L11; hsa-let-7b and hsa-miR-125b targeted the genes CDC25A, CDK6, and LIN28A. Expression of three miRNAs in GSE41321 was consistent with that in GSE7072., Conclusions: Several critical miRNAs were identified in RB progression. Hsa-miR-373 might regulate RB invasion and metastasis, hsa-miR-181a might involve in the CDKN1B-mediated cell cycle pathway, and hsa-miR-125b and hsa-let-7b might serve as tumor suppressors by coregulating CDK6, CDC25A, and LIN28A. The miRNAs hsa-miR-25, hsa-miR-18a, and hsa-miR-20a might exert their function by coregulating BCL2L1.

Purpose: To study the presenting signs of Retinoblastoma in Egypt at Egypt's main pediatric oncology referral center., Methods: This is a prospective descriptive study (hospital-based registry) conducted at Children's Cancer Hospital Egypt between July 2007 and December 2012., Results: Out of 262 patients diagnosed with retinoblastoma, 244 were suffering from intra-ocular disease at presentation. One hundred thirty-nine (57%) patients presented with unilateral disease, while 105 (43%) suffered bilateral disease. The mean age at presentation was 20.6 ± 17 months, averaging 18.87 ± 11.76 months for bilateral and 25.72 ± 18.78 months for unilateral disease. The most common clinical presentation was leukocoria in 180 (73.8%) patients, strabismus in 32 (13.1%) patients and decreased visual acuity in 12 (4.9%) patients. Group D and E disease represented 62% of all affected eyes. Patients with advanced disease (Group C-E) had longer duration of symptoms., Conclusion: In Egypt, retinoblastoma patients present more frequently with advanced disease. There is an ever-increasing need to develop a national team dedicated to studying disease significance and formulating a national awareness program., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The early age at retinoblastoma occurrence, the most common eye malignancy in childhood, suggests that perinatal factors may contribute to its etiology., Methods: In a large multicenter study of non-familial retinoblastoma, we conducted structured interviews with the parents of 280 cases and 146 controls to elicit information on health during the perinatal period. We used unconditional logistic regression to assess associations between retinoblastoma and parental fertility treatment, birth control use in the year prior to pregnancy, maternal health conditions and the use of prescription medications during pregnancy, and whether mothers breastfed the index child., Results: Bilateral retinoblastoma was related to maternal underweight (body mass index <18.5) prior to pregnancy [Odds Ratio (OR) = 4.5, 95 % confidence interval (CI) 1.0, 20]. With regards to unilateral retinoblastoma, we observed a negative association with the use of condoms in the year prior to pregnancy (OR = 0.4, CI 0.2, 0.9), and a trend towards a positive association with maternal diabetes (OR = 2.2, CI 0.8, 6.6)., Conclusions: Results from our study suggest a role for several maternal health and reproductive factors. Given that there are few epidemiologic studies of retinoblastoma, our results require replication in studies which utilize medical record review.

Purpose: To accurately map the retinal area covered by tumor in a prospectively enrolled cohort of children diagnosed with retinoblastoma., Methods: Orbital MRI in 106 consecutive retinoblastoma patients (44 bilateral) was analyzed. For MRI-visible tumors, the polar angle and angle of eccentricity of points defining tumor perimeter on the retina were determined by triangulation from images in three orthogonal planes. The centroid of the mapped area was calculated to approximate tumor origin, and the location and cumulative tumor burden were analyzed in relation to mutation type (germline vs. somatic), tumor area, and patient age at diagnosis. Location of small tumors undetected by MRI was approximated with fundoscopic images., Results: Mapping was successful for 129 tumors in 91 eyes from 67 patients (39 bilateral, 43 germline mutation). Cumulative tumor burden was highest within the macula and posterior pole and was asymmetrically higher within the inferonasal periphery. Tumor incidence was lowest in the superotemporal periphery. Tumor location varied with age at diagnosis in a complex pattern. Tumor location was concentrated in the macula and superonasal periphery in patients <5.6 months, in the inferotemporal quadrant of the posterior pole in patients 5.6-8.8 months, in the inferonasal quadrant in patients 8.8-13.2 months, and in the nasal and superotemporal periphery in patients >13.2 months. The distribution of MRI-invisible tumors was consistent with the asymmetry of mapped tumors., Conclusions: MRI-based mapping revealed a previously unrecognized pattern of retinoblastoma localization that evolves with age at diagnosis. The structured spatiotemporal distribution of tumors may provide valuable clues about cellular or molecular events associated with tumorigenesis in the developing retina.

Purpose: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development., Methods: The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis., Results: Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous., Conclusions: OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.

Purpose: Previous studies have suggested a role for parental diet in childhood cancer prevention, but there are few studies of retinoblastoma. The aim of this study was to examine the relation between maternal diet and unilateral retinoblastoma., Methods: A case-control study of 163 unilateral RB cases and 136 controls ascertained information on maternal diet during pregnancy using a standardized food frequency questionnaire. Logistic regression was used to assess the relation between retinoblastoma and food groups and dietary patterns., Results: We observed a negative association between retinoblastoma and intake of fruit [odds ratio (OR) 0.38, 95 % confidence interval (CI) 0.14-1.02]. Positive associations were seen with intake of cured meats (OR 5.07, 95 % CI 1.63-15.70) and fried foods (OR 4.89, 95 % CI 1.72-13.89). A food pattern of high fruits and vegetables and low fried food and sweets was negatively associated with disease (OR 0.75, 95 % CI 0.61-0.92)., Conclusion: Our study provides preliminary evidence that mothers who consume diets higher in fruit and lower in fried foods and cured meats during pregnancy may reduce the risk of unilateral retinoblastoma in their offspring.

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing)., Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models., Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01)., Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germline mutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An association between mutations in germline cells and aging has been demonstrated. This suggests a higher incidence of childhood cancer including retinoblastoma among children of older parents., Materials and Methods: In the present study we aimed to determine the association of paternal and maternal age with an increased risk of retinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who were born during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studying the mean age of parents and in order to know whether parental age of patients is different from parental age of control group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated., Results: The results of statistical analysis including the study of mean parental age by the use of (t-test) compare averages test showed a significant difference between parental ages of patients and controls. Logistic regression showed that coefficients were significant for maternal but not paternal age., Conclusions: Our findings indicate that advanced maternal age can increase the risk of retinoblastoma in offspring, but the paternal age has no significant effect.

Purpose of Review: Retinoblastoma is the most common malignant intraocular tumor of childhood. Treatment and diagnostic modalities associated to this condition are changing rapidly as our understanding of this condition crystallizes. The purpose of this review is to provide an update of the current understanding of retinoblastoma., Recent Findings: Knowledge on tumorigenesis and genomic expression has expanded tremendously with the development of a mouse model for retinoblastoma. Tumor hypoxia has been identified as a significant step in the tumor progression and a novel target for future treatments. Current globe-sparing therapies, including periocular carboplatin, selective ophthalmic artery chemoreduction, intravitreal melphalan, and focal consolidation are being used and investigated actively. Diagnosis and the management of retinoblastoma is also undergoing major advances including wide-field photography, autofluorescence, and high-resolution optical coherence tomography., Summary: Progressive advances in the understanding of retinoblastoma pathogenesis continue to lead treatment strategies. Improvements in the diagnosis and management of retinoblastoma are improving morbidity and mortality associated to this condition in the developed nations. However, it is of outmost importance to flatten the international boundaries to offer prompt care to retinoblastoma children in underdeveloped communities.

Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression-based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.

Background: The risk factors for sporadic (ie, non-familial) retinoblastoma remain largely unknown., Objectives: We examined the relationship between paternal occupational exposures from jobs held 10 years and 1 year prior to conception and the risk of sporadic bilateral retinoblastoma in children., Methods: Paternal occupational data were obtained for 198 incident cases diagnosed with sporadic bilateral retinoblastoma from January 1998 to May 2006 and 245 referral-based controls from the case child's relatives and friends who were matched to 135 of the cases on birth year. Industrial hygienists independently assigned exposure scores for nine agents. Adjusted ORs and 95% CIs were computed using logistic regression models, using the full sample of cases and controls as well as subset of cases with matched controls only., Results: There was some indication of an elevated risk associated with paternal pesticide exposure in the 10 years prior to conception (OR=1.64; 95% CI 1.08 to 2.50) as well as in the year before conception (OR=2.12; 95% CI 1.25 to 3.61). However, results for pesticide exposure were inconsistent and varied by analysis approach. An increased risk was also observed for non-welding metal exposure during the 10 years prior to conception in the full (OR=1.35; 95% CI 0.86 to 2.12) and matched (OR=1.40; 95% CI 0.82 to 2.37) samples, but not in the year before conception. Exposure-response trends were observed for pesticides and non-welding metal exposures., Conclusions: Our findings suggest a potential role of paternal occupational exposures to non-welding metals and perhaps pesticides in the aetiology of childhood retinoblastoma.

Purpose: We conducted a case-control study to examine the role of parents' nutrient intake before their child's conception in the child's risk of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation., Methods: Parents of 206 cases from 9 North American institutions and 269 friend and relative controls participated; fathers of 182 cases and 223 controls and mothers of 202 cases and 260 controls provided useable information in telephone interviews on their diet in the year before the child's conception. We also asked parents about supplements, a significant source of nutrients in users., Results: Father's intake of dairy-associated nutrients and his use of calcium supplements were associated with decreased risk, while his intake of copper, manganese, and vitamin E was associated with increased risk. Mother's use of multivitamins close to conception was associated with lower risk as was her intake of several micronutrients found in these supplements. In analyses to elucidate the primary factor from multiple correlated factors, the most robust findings were for father's calcium intake (adjusted OR = 0.46-0.63 for 700 mg increase) and calcium supplement use (OR = 0.35-0.41) and mother's multivitamin use (ORs 0.28-0.48)., Conclusions: There are few directly relevant studies but some data indirectly support the biologic plausibility of the inverse associations with father's calcium intake and mother's use of multivitamins; however, we cannot rule out contributions of bias, confounding, or chance. Our findings provide a starting point for further investigation of diet in the etiology of retinoblastoma and new germline mutation generally.

Background: The incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring., Methods: The authors used a case-control study design to examine the association between retinoblastoma risk and maternal variations in the folate-metabolizing genes methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution at nucleotide 677 [MTHFR677C→T]; reference single nucleotide polymorphism rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron 1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with newly diagnosed unilateral retinoblastoma were enrolled in an institutional review board-approved study along with a control group of 97 mothers who had healthy children. Mothers were interviewed regarding perinatal characteristics, including use of prenatal vitamin supplements, and gave peripheral blood samples, which were used for polymerase chain reaction-based genotyping of rs1801133 and rs70991108., Results: The risk of having a child with unilateral retinoblastoma was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95% confidence interval, 1.89-7.55; P = .0002), even after controlling for the child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32-5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of having a child with retinoblastoma., Conclusions: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Prenatal ingestion of synthetic folic acid supplements may be associated with increased risk for early childhood carcinogenesis in a genetically susceptible subset of the population., (Copyright © 2012 American Cancer Society.)

Purpose: The etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children., Methods: We identified 609 retinoblastoma cases (420 unilateral, 187 bilateral, and 2 with laterality unknown) from California Cancer Registry records of diagnoses 1988-2007 among children < 6 years of age. We randomly selected 209,051 controls from California birth rolls. The source of most study data was birth certificates. Multivariable logistic regression was used to examine associations between retinoblastoma and perinatal characteristics., Results: Bilateral retinoblastoma was associated with greater paternal age [for fathers over 35, crude odds ratio (OR) = 1.73, 95 % confidence interval (CI) 1.20, 2.47] and with twin births (OR = 1.93, 95 % CI 0.99, 3.79). Among unilateral cases, we observed an increased risk among children of US-born Hispanic mothers (OR = 1.34, 95 % CI 1.01, 1.77) while a decreased risk was observed for infants born to mothers with less than 9 years of education (OR = 0.70, 95 % CI 0.49, 1.00), a group that consisted primarily of mothers born in Mexico. We observed that maternal infection in pregnancy with any STD (OR = 3.59, 95 % CI 1.58, 8.15) was associated with bilateral retinoblastoma., Conclusions: This study supports the findings of previous investigations reporting associations between parental age, HPV infection, and retinoblastoma.

Retinoblastoma is a rare primary intraocular malignancy. Presentation in the neonatal period is not common. With improved genetic testing, screening of the unborn child and neonate is taking on a greater role in the management of these patients. Treatment of retinoblastoma in the neonate is complex and requires a multidisciplinary and highly individualized approach. If possible, focal modalities should be used and external beam radiation avoided. Systemic intravenous chemotherapy may be necessary with regimens including carboplatin, vincristine and etoposide. Such cases are best managed by specialist centers with access to experts in oncology, ophthalmology, radiation therapy, genetics, pathology and anesthesia., (Copyright © 2012. Published by Elsevier Ltd.)

Background: Retinoblastoma (RB) is the most frequent eye tumour in children, with an incidence of 1 in 15-20,000 births. It accounts for 11% of all cancers in the first year of life. Except for the hereditary forms, its causes are not well-known. Studies have recently suggested an increased risk of RB among children born after IVF, but the relevant literature is sparse. We assessed the association between infertility treatment, subfertility and RB., Methods: We included all children living in France diagnosed with RB between 1 January 2000 and 31 December 2006 at the Institut Curie, the national reference centre for RB diagnosis and treatment. We used multiple logistic regression to compare them with a national sample of births in France in 1998 and 2003 (n = 28 170)., Results: The study included 244 non-familial RB cases. The risk of RB increased with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval (CI) 1.33-3.22 at 35-39 years compared with younger than 25 years and adj OR = 2.42, 95% CI 1.22-4.81 at 40 years or older], but the associations with IVF (adj OR = 1.37, 95% CI 0.64-2.95) and ovarian stimulation or intrauterine insemination (adj OR = 1.35, 95% CI 0.77-2.38) were not statistically significant after adjustment for maternal age and tobacco use. Among women who had no infertility treatment, the risk of RB was significantly increased when time to pregnancy exceeded 24 months (adj OR = 2.02, 95% CI 1.17-3.48) compared with time to pregnancy ≤ 24 months., Conclusions: Our study did not observe a significantly increased risk of RB associated with infertility treatment, in particular with IVF. But we did find an increased risk for women for whom time to pregnancy exceeded 24 months.

We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate the role of parents' diet before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; of these, fathers of 184 cases and 223 controls and mothers of 204 cases and 260 controls answered a food frequency questionnaire administered by phone about their diet in the year before the child's conception. Cases provided DNA for RB1 mutation testing. We assessed parents' diet by examining 19 food groups. Father's intake of dairy products and fruit was associated with decreased risk and cured meats and sweets with increased risk. Mother's intake was not associated with disease for any food group. Considering analyses adjusted for the other food groups significantly associated with disease, energy intake, and demographic characteristics as well as more fully adjusted models, the associations with father's dairy products and cured meat intake were the most robust. In the fully adjusted, matched analysis, the odds ratios per daily serving were 0.70 (95% confidence interval (CI) 0.49-1.00, P = 0.047) for dairy products and 5.05 (CI 1.46-17.51, P = 0.01) for cured meat. The pattern of associations with paternal but not maternal diet is consistent with the fact that 85% of new germline RB1 mutations occur on the father's allele. As few human data exist on the role of diet in any condition resulting from new germ-cell mutation, additional studies will be needed to replicate or refute our findings., (Copyright © 2012 Wiley Periodicals, Inc.)

Birth defects may influence the risk of childhood cancer development through a variety of mechanisms. The rarity of both birth defects and childhood cancers makes it challenging to study these associations, particularly for the very rare instances of each. To address this limitation, the authors conducted a record linkage-based cohort study among Texas children born between 1996 and 2005. Birth defects in the cohort were identified through the Texas Birth Defects Registry, and children who developed cancer were identified by using record linkage with Texas Cancer Registry data. Over 3 million birth records were included; 115,686 subjects had birth defects, and there were 2,351 cancer cases. Overall, children with a birth defect had a 3-fold increased risk of developing cancer (incidence rate ratio (IRR) = 3.05, 95% confidence interval (CI): 2.65, 3.50), with germ cell tumors (IRR = 5.19, 95% CI: 2.67, 9.41), retinoblastomas (IRR = 2.34, 95% CI: 1.21, 4.16), soft-tissue sarcomas (IRR = 2.12, 95% CI: 1.09, 3.79), and leukemias (IRR = 1.39, 95% CI: 1.09, 1.75) having statistically significant elevated point estimates. All birth defect groups except for musculoskeletal had increased cancer incidence. Untangling the strong relation between birth defects and childhood cancers could lead to a better understanding of the genetic and environmental factors that affect both conditions.

Trilateral retinoblastoma is the association of hereditary bilateral or unilateral retinoblastoma with a pineal neuroblastic tumour. We describe two cases of trilateral retinoblastoma from a total of 141 cases of retinoblastoma seen over an 8.5 year period. Both had a fatal outcome, with survival times of only 4 and 8 months respectively.

Although ionizing radiation induces germline mutations in animals, human studies of radiation-exposed populations have not detected an effect. We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate gonadal radiation exposure of parents from medical sources before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; fathers of 184 cases and 223 friend and relative controls and mothers of 204 cases and 260 controls provided information in telephone interviews on their medical radiation exposure. Cases provided DNA for RB1 mutation testing. Of common procedures, lower gastrointestinal (GI) series conferred the highest estimated dose to testes and ovaries. Paternal history of lower GI series was associated with increased risk of retinoblastoma in the child [matched odds ratio (OR) = 3.6, 95% confidence interval (CI) = 1.2-11.2, two-sided p = 0.02], as was estimated total testicular dose from all procedures combined (OR for highest dose=3.9, 95% CI = 1.2-14.4, p = 0.02). Maternal history of lower GI series was also associated with increased risk (OR = 7.6, 95% CI = 2.8-20.7, p < 0.001) as was the estimated total dose (OR for highest dose = 3.0, 95% CI = 1.4-7.0, p = 0.005). The RB1 mutation spectrum in cases of exposed parents did not differ from that of other cases. Some animal and human data support our findings of an association of gonadal radiation exposure in men and women with new germline RB1 mutation detectable in their children, although bias, confounding, and/or chance may also explain the results., (Copyright © 2010 UICC.)

Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3-6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0-45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.

Objectives: To examine the association between paternal occupational exposures and retinoblastoma using birth registration data for cases from the National Registry of Childhood Tumours (NRCT) and controls from the general population of Great Britain., Methods: A case-control study of paternal occupational data for 1318 cases of retinoblastoma, born and diagnosed in Great Britain between 1962 and 1999, and 1318 controls matched on sex, date of birth and birth registration sub-district. Paternal occupations at birth were grouped according to inferred exposure using an occupational exposure classification scheme. A conditional (matched) case-control analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for each paternal occupational exposure group., Results: For non-heritable retinoblastoma, a statistically significant increased risk was found with father's definite occupational exposure to oil mists in metal working (OR = 1.85 (95% CI 1.05 to 3.36)). Together with a (non-significant) risk (OR = 1.64 (0.73 to 3.83)) amongst the heritable cases, this occupational exposure was also associated with a significant increased risk when all retinoblastoma cases were considered together (OR = 1.77 (1.12 to 2.85)). No statistically significant associations were observed for other exposure groups., Conclusions: Our finding for exposure to oil mists in metal working (a subset of metal workers) is not directly comparable to those for metal working previously reported in the literature. Overall, our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for retinoblastoma, however, the study has low power and other methodological limitations.

There is a clear dividing line in the group of actions aimed at solving sterility, and the techniques aimed at generating embryos to be transferred to a womb. The dividing line is now clearly established by science. The growing alarm among paediatricians raised by the higher risk of malformations and diseases in children when generated in vitro, with respect to those normally engendered, is leading to the need to clearly establish the consequences of in vitro technologies and informing society in an honest way. Two types of lack of exchange of information, cellular and molecular, cause the detected defects. In the fi rst place it is clear that both gametes should recognize each other when adequately mature and in the appropriate natural environment. In vitro technologies force these conditions and either one or both gametes might be impaired and consequently negative effects for the child might be caused. In the second place both embryo and maternal womb are deprived of that early mother-child communication facilitating implantation.

We have successfully imaged the retinal tumor in a mouse model using an ultra-high resolution spectral-domain optical coherence tomography (SD-OCT) designed for small animal retinal imaging. For segmentation of the tumor boundaries and calculation of the tumor volume, we developed a novel segmentation algorithm. The algorithm is based on parametric deformable models (active contours) and is driven by machine learning-based region classification, namely a Conditional Random Field. With this algorithm we are able to obtain the tumor boundaries automatically, while the user can specify additional constraints (points on the boundary) to correct the segmentation result, if needed. The system and algorithm were successfully applied to studies on retinal tumor progression and monitoring treatment effects quantitatively in a mouse model of retinoblastoma.

Purpose: The aim of this study is to analyze the results and the complications of radiotherapy in the treatment of retinoblastoma., Patients and Methods: Between 1994 and 2004, 40 children received radiotherapy for a retinoblastoma in Salah Azaiz Institute. The average age of the patients was 36 months (four to 132 months). There were 16 girls and 24 boys. Sixteen children presented a bilateral disease and 24 children a unilateral disease. Twenty eyes and thirty-six orbital cavities in 40 children with retinoblastoma were treated by radiotherapy. One child with a unilateral anterior retinoblastoma was treated with 106 ruthenium brachytherapy. External radiotherapy has been used to treat the 39 patients. In 20 cases the irradiation was conservative and in 36 cases postoperatively. The latter (n=36) presented at least one risk factor of relapses noted in the histological examination. The average dose was 44 Gy (1.8 to 2 Gy per fraction, five fractions weekly). This radiotherapy was associated with chemotherapy in 24 cases., Results: Thirty-five children were followed with an average follow-up of 53 months (3-108 months). The average delay of relapses was of 10 months (two to 26 months). We found four orbital relapses and seven metastasis in nine children. The conservation of the eye with a useful visual field was noted in 18 cases among the 20 conservative irradiated eyes. The major therapeutic complication was the growth defect of the bones face. A femoral bone sarcoma was noted five years after the end of the irradiation and chemotherapy in one case., Conclusion: If the radiotherapy offers the advantage of the functional conservation and the improvement of the local control, its indications are more and more restricted in favor of the other therapeutic methods (chemotherapy, thermochemotherapy) and this considering the iatrogene risk. The development of new techniques of brachytherapy and the progresses of the conformational radiotherapy appear to reduce considerably this risk.

Purpose: To report the incidence of new tumor formation in hereditary retinoblastoma patients treated with primary systemic chemotherapy., Design: Noncomparative retrospective case series., Participants: Fifty-eight consecutive patients with hereditary retinoblastoma treated with primary systemic chemotherapy., Methods: The charts of 58 consecutive patients with hereditary retinoblastoma treated between January 1996 and August 2005 were reviewed. Data extracted included gender, age at diagnosis, family history of retinoblastoma, laterality of disease, tumors per eye, Reese-Ellsworth grouping of affected eyes, starting and ending dates for chemotherapy, number of cycles of chemotherapy, chemotherapy regimen, need for external beam radiotherapy and/or enucleation, and development and location (macula, midzone, and periphery) of new tumors after the start of systemic chemotherapy., Main Outcome Measure: New tumor formation after treatment with primary systemic chemotherapy., Results: Of the 58 patients, 48 had bilateral involvement at diagnosis. Median age at diagnosis was 6.6 months. Thirteen patients had a positive family history. Of the eyes with tumor (n = 106) at diagnosis, 52 (49%) were in Reese-Ellsworth groups I to III, whereas 54 (51%) were in group IV or V. Seven patients (12%) with a median age of 1.6 months at diagnosis formed 36 new tumors in 11 eyes after the start of chemotherapy. Median time from initiation of chemotherapy to detection of the first new tumor was 3 months (range, 1-15). Cumulative incidence of new tumor formation at 2 years was 10+/-3%. An age of <6 months at diagnosis, family history of retinoblastoma, and Reese-Ellsworth grouping of I to III were found to correlate significantly with an increased incidence of new tumor formation (P<0.001, P<0.001, and P = 0.021, respectively). Median follow-up for all patients was 5 years (range, 1-10.1)., Conclusion: New tumors continue to form in patients with hereditary retinoblastoma despite treatment with primary systemic chemotherapy. Younger patients and those with a positive family history are more likely to have new tumors formed. However, chemotherapy may impact small previously undetected lesions by slowing their growth and facilitating later focal consolidation.

Background: Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries., Methods: In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently., Results: There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis., Conclusion: Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

Serum superoxide dismutase and catalase assays were performed using spectrophotometry in 60 adults and children with benign or malignant tumors and in controls. There was a statistically significant difference in the antioxidative status of children with intraocular tumors (primary retinoblastoma) compared with children without tumors. The difference was not significant in adults. These enzymes may be of value in the early diagnosis of malignant intraocular tumor, especially retinoblastoma.

Assisted reproductive technology (ART) has become the standard of care for the treatment of many types of infertility. As a result, the numbers of children born after ART worldwide has escalated dramatically, and attention has turned to the potential risks of these procedures to the health and development of the children. In addition to the well-established risks of multiple gestations, recent reports have suggested a link between ART and rare disorders of imprinting including Beckwith-Wiedemann syndrome and Angelman syndrome. Here we review molecular mechanisms of genomic imprinting, consider how ART procedures could influence imprinting of gametes and embryos, and review the reports connecting imprinting disorders to ART. We highlight the importance of long-term follow-up of children born after ART, and emphasize the need for an improved understanding of the mechanisms of imprinting at the molecular level so that methods to prevent disruption of this critical epigenetic process can be developed.

Objective: Little is known about the causes of sporadic (noninherited) retinoblastoma. Rates seem to be somewhat higher among poorer populations in Mexico. Fruits and vegetables are important sources of carotenoids and folate. We examined whether decreased gestational maternal intake of fruits and vegetables may contribute to development of sporadic retinoblastoma., Methods: At the Instituto Nacional de Pediatria in Mexico City, we conducted a hospital-based case-control study to evaluate prenatal maternal diet. We examined dietary intake of fruits and vegetables of mothers of 101 children with retinoblastoma and 172 control children using a dietary recall questionnaire and published food nutrient content tables., Results: The reported number of mean daily servings of fruits and vegetables was lower among case mothers when compared with control mothers [vegetables: 2.28 in controls, 1.75 in cases (P < 0.01); fruits: 2.13 in controls, 1.59 in cases (P = 0.07)]. Mean daily maternal folate intake from both vegetables and fruits was higher in controls (103 microg) than in cases (48 microg; P < 0.05). Risk for having a child with retinoblastoma was increased for mothers consuming fewer than 2 daily servings of vegetables [odds ratios (OR), 3.4; 95% confidence interval (95% CI), 2.0-6.0] or with a low intake of folate (OR, 3.9; 95% CI, 2.1, 7.3), or lutein/zeaxanthin (OR, 2.6; 95% CI, 1.5-4.6) derived from fruits and vegetables., Conclusions: Decreased intake of vegetables and fruits during pregnancy and the consequent decreased intake of nutrients such as folate and lutein/zeaxanthin, necessary for DNA methylation, synthesis, and retinal function, may increase risk for having a child with sporadic retinoblastoma.

Aims: To estimate the frequency of childhood retinoblastoma among children conceived by in vitro fertilization (IVF)., Methods: Using the United Kingdom-based General Practice Research Database (GPRD), we identified all live births, cases of retinoblastoma and IVF procedures occurring between January 1989 and December 2001., Results: We identified 0 cases of retinoblastoma among 176 children conceived by IVF (Risk = 0/176, one-sided 97.5% CI 0, 0.02) and 24 cases of retinoblastoma diagnosed before age 5 years among 358,094 children not conceived by IVF (6.7 cases per 100,000 births [95% CI 4.5, 10])., Conclusions: These data provide some reassurance that children born as a result of IVF are not at markedly increased risk of retinoblastoma.