Risk Factors for Acute Leukemia in Children: A Review

Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics

Membrane Paradigm and Horizon Thermodynamics in Lanczos-Lovelock gravity

We study the membrane paradigm for horizons in Lanczos-Lovelock models of gravity in arbitrary D dimensions and find compact expressions for the pressure p and viscosity coefficients \eta and \zeta of the membrane fluid. We show that the membrane pressure is intimately connected with the Noether charge entropy S_Wald of the horizon when we consider a specific m-th order Lanczos-Lovelock model, through the relation pA/T=(D-2m)/(D-2)S_Wald, where T is the temperature and A is the area of the horizon. Similarly, the viscosity coefficients are expressible in terms of entropy and quasi-local energy associated with the horizons. The bulk and shear viscosity coefficients are found to obey the relation \zeta=-2(D-3)/(D-2)\eta.Comment: v1: 13 pages, no figure. (v2): refs added, typos corrected, new subsection added on the ratio \eta/s. (v3): some clarification added, typos corrected, to appear in JHE

Maternal Exposure to Occupational Solvents and Childhood Leukemia

Many organic solvents are considered probable carcinogens. We carried out a population-based case–control study including 790 incident cases of childhood acute lymphoblastic leukemia and as many healthy controls, matched on age and sex. Maternal occupational exposure to solvents before and during pregnancy was estimated using the expert method, which involves chemists coding each individual’s job for specific contaminants. Home exposure to solvents was also evaluated. The frequency of exposure to specific agents or mixtures was generally low. Results were generally similar for the period ranging from 2 years before pregnancy up to birth and for the pregnancy period alone. For the former period, the odds ratio (OR), adjusted for maternal age and sex, for any exposure to all solvents together was 1.11 [95% confidence interval (CI), 0.88–1.40]. Increased risks were observed for specific exposures, such as to 1,1,1-trichloroethane (OR = 7.55; 95% CI, 0.92–61.97), toluene (OR = 1.88; 95% CI, 1.01–3.47), and mineral spirits (OR = 1.82; 95% CI, 1.05–3.14). There were stronger indications of moderately increased risks associated with exposure to alkanes (C5–C17; OR = 1.78; 95% CI, 1.11–2.86) and mononuclear aromatic hydrocarbons (OR = 1.64; 95% CI, 1.12–2.41). Risk did not increase with increasing exposure, except for alkanes, where a significant trend (p = 0.04) was observed. Home exposure was not associated with increased risk. Using an elaborate exposure coding method, this study shows that maternal exposure to solvents in the workplace does not seem to play a major role in childhood leukemia

Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study

INTRODUCTION: Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine. METHODS: Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival. RESULTS: The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00). CONCLUSION: This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted

Cancer risks following diagnostic and therapeutic radiation exposure in children

The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life

Analytical study on holographic superconductors in external magnetic field

We investigate the holographic superconductors immersed in an external magnetic field by using the analytical approach. We obtain the spatially dependent condensate solutions in the presence of the magnetism and find analytically that the upper critical magnetic field satisfies the relation given in the Ginzburg-Landau theory. We observe analytically the reminiscent of the Meissner effect where the magnetic field expels the condensate. Extending to the D-dimensional Gauss-Bonnet AdS black holes, we examine the influence given by the Gauss-Bonnet coupling on the condensation. Different from the positive coupling, we find that the negative Gauss-Bonnet coupling enhances the condensation when the external magnetism is not strong enough.Comment: revised version, to appear in JHE

Radon and childhood cancer

British Journal of Cancer (2002) 87, 1336–1337. doi:10.1038/sj.bjc.6600671 www.bjcancer.co

Lovelock theories, holography and the fate of the viscosity bound

We consider Lovelock theories of gravity in the context of AdS/CFT. We show that, for these theories, causality violation on a black hole background can occur well in the interior of the geometry, thus posing more stringent constraints than were previously found in the literature. Also, we find that instabilities of the geometry can appear for certain parameter values at any point in the geometry, as well in the bulk as close to the horizon. These new sources of causality violation and instability should be related to CFT features that do not depend on the UV behavior. They solve a puzzle found previously concerning unphysical negative values for the shear viscosity that are not ruled out solely by causality restrictions. We find that, contrary to previous expectations, causality violation is not always related to positivity of energy. Furthermore, we compute the bound for the shear viscosity to entropy density ratio of supersymmetric conformal field theories from d=4 till d=10 - i.e., up to quartic Lovelock theory -, and find that it behaves smoothly as a function of d. We propose an approximate formula that nicely fits these values and has a nice asymptotic behavior when d goes to infinity for any Lovelock gravity. We discuss in some detail the latter limit. We finally argue that it is possible to obtain increasingly lower values for the shear viscosity to entropy density ratio by the inclusion of more Lovelock terms.Comment: 42 pages, 17 figures, JHEP3.cls. v2: reference adde

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women

Background: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. Methods and Results: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T→C (rs799908:T→C), c.-2265C→T (rs11655505:C→T), c.-2004A→G (rs799906:A→G) and c.-1896(ACA) 1→(ACA) 2 (rs8176071:(ACA) 1→(ACA) 2) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% Cl 0.69 to 0.93; p = 0.003) which was more evident among women aged ≥45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% Cl 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged ≥45 years without a family history of breast cancer (OR = 0.64, 95% Cl 0.46 to 0.89; p = 0.008). Conclusion: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C→T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.published_or_final_versio