Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

[[abstract]]Background: Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. Methods: We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002. Results: We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. Conclusions: These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis

Genetic variation in the extended major histocompatibility complex and susceptibility to childhood acute lymphoblastic leukemia: A review of the evidence

The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL), is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2–5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (MHC), an approximately 7.6 Mb region that is well-known for its high-density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA). First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C) and class II (HLA-DR, HLA-DQ, and HLA-DP) molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk

Weather and Health Symptoms

Weather affects the daily lives of individuals. However, its health effects have not been fully elucidated. It may lead to physical symptoms and/or influence mental health. Thus, we evaluated the association between weather parameters and various ailments. We used daily reports on health symptoms from 4548 individuals followed for one month in October of 2013, randomly sampled from the entirety of Japan. Weather variables from the monitoring station located closest to the participants were used as weather exposure. Logistic mixed effects model with a random intercept for each individual was applied to evaluate the effect of temperature and humidity on physical symptoms. Stratified analyses were conducted to compare weather effects by sex and age group. The lag day effects were also assessed. Joint pain was associated with higher temperature (1.87%, 95% CI = 1.15 to 2.59) and humidity (1.38%, 95% CI = 0.78 to 2.00). Headaches was increased by 0.56% (95% CI = −0.55 to 1.77) per 1 °C increase in the maximum temperature and by 1.35% per 1 °C increase in dew point. Weather was associated with various physical symptoms. Women seem to be more sensitive to weather conditions in association with physical symptoms, especially higher humidity and lower temperature

Imaging Characteristics of Driver Mutations in EGFR, KRAS, and ALK among Treatment-Naïve Patients with Advanced Lung Adenocarcinoma.

This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB-IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups' characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB-IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal invasion, and lymphangitis. These mutation-specific imaging characteristics may be related to the biological differences between these cancers

Evaluating the seasonality of growth in infants using a mobile phone application

Abstract It has been observed that growth velocity of toddlers and school children shows seasonal variation, while such seasonality is unknown in infants. The aim of this study was to examine whether growth velocity (length and weight) of infants differs by seasons. We assessed longitudinal measurement data obtained for 9,409 Japanese infants whose parents used the mobile phone application, “Papatto Ikuji”, during the period from January 2014 to October 2017. On average, each infant had 4.8 entries for length and 5.4 entries for weight. The mean daily change in sex- and age-adjusted z-scores between two time points was estimated as the growth velocity during that period: ΔLAZ/day and ΔWAZ/day for length and weight, respectively. We analyzed 20,007 ΔLAZ/day (mean, −0.0022) and 33,236 ΔWAZ/day (mean, 0.0005) measurements, and found that ΔLAZ/day showed seasonal differences with increases during summer. We conducted a multilevel linear regression analysis, in which effects of age, sex, nutrition and season of birth were adjusted, showing significant difference in ΔLAZ/day between winter and summer with a mean ΔLAZ/day difference of 0.0026 (95%CI 0.0015 to 0.0036; P < 0.001). This seasonal difference corresponded to 13% of the average linear growth velocity in 6-month-old infants. A modest effect of nutrition on linear growth was observed with a mean ΔLAZ/day difference of 0.0015 (95%CI 0.0006 to 0.0025; P < 0.001) between predominantly formula-fed infants and breastfed infants. In conclusion, we observed that linear growth, but not weight gain, of Japanese infants showed significant seasonality effects represented by increases in summer and decreases in winter

Association between very advanced maternal age and adverse pregnancy outcomes: a cross sectional Japanese study

Abstract Background While several studies have demonstrated the increased risk of pregnancy complications for women of advanced age, few studies have focused on women with very advanced age (≥ 45), despite the increasing rate of pregnancy among such women. Furthermore, how such risks of increase in age differ by maternal characteristics are also poorly understood. Thus, we aimed to clarify pregnant outcomes among women with very advanced age and how the effect of age differs by method of conception and parity. Methods We used the national multicenter Japan Society of Obstetrics and Gynecology perinatal database, including 365,417 women aged 30 years or older who delivered a singleton between 2005 and 2011. We divided women into four groups based on age (years): 30–34, 35–39, 40–44, and ≥45, and compared risk of adverse birth outcomes between the groups using Poisson regression. Effect modification by parity and use of assisted reproductive technology (ART) was also evaluated. Results: Compared with women aged 30–34 years, women aged 45 or older had higher risk of emergency cesarean delivery [adjusted risk ratio (aRR): 1.77, 95% confidence interval (95% CI): 1.58–1.99], preeclampsia (aRR: 1.86, 95% CI: 1.43–2.42), severe preeclampsia (aRR: 2.03, 95% CI: 1.31–3.13), placenta previa (aRR: 2.17, 95% CI: 1.60–2.95), and preterm birth (aRR: 1.20, 95% CI: 1.04–1.39). The effect of older age on risk of emergency cesarean section, preeclampsia, and preterm birth were significantly greater among those who conceived naturally compared to those who conceived by ART. The effect on emergency cesarean section was stronger among primiparous women, whereas the risk of preeclampsia associated with older age was significantly greater among multiparous women. Conclusions Very advanced maternal age (≥ 45) was related to greater risk for adverse birth outcomes compared to younger women, especially for maternal complications including cesarean section, preeclampsia, severe preeclampsia, and placenta previa. The magnitude of the influence of age also differed by conception method and by parity