Network analysis of smoking-related sleep characteristics in Chinese adults.

The associations between multiple sleep characteristics and smoking behavior are inconsistent, and it is unclear which sleep characteristics are most crucial for tobacco prevention. This study aimed to explore the associations between smoking status/intensity and multiple sleep characteristics and to identify the potential core domain of smoking-related sleep using network analysis. Data were obtained from a survey of cancer-related risk factors among Chinese adults. Logistic regression models were used to quantify the associations between sleep characteristics and smoking status/intensity. Network analyses were employed to identify the core sleep characteristics. A total of 5,228 participants with a median age of 44 years old were included in the study. Current smoking was significantly positively associated with long nap time, difficulty falling asleep, late bedtime, getting up after 7 am, and waking up earlier than expected. There was significant positive association between current smoking and short sleep duration in young adults under 45 years old. Late bedtime and getting up after 7 am were only associated with current heavy smoking, but not current light smoking. Network analyses showed that multiple smoking-related sleep characteristics were interconnected, with difficulty falling asleep and late bedtime as central characteristics in the network. The study found that the associations between sleep characteristics and smoking varied by age and smoking intensity and highlights the potential benefits of sleep health promotion in smoking cessation, with a particular focus on difficulty falling asleep and late bedtime.

Risk-Adapted Starting Age of Personalized Lung Cancer Screening: A Population-Based, Prospective Cohort Study in China.

BACKGROUND: The current one-size-fits-all screening strategy for lung cancer is not suitable for personalized screening. RESEARCH QUESTION: What is the risk-adapted starting age of lung cancer screening with comprehensive consideration of risk factors? STUDY DESIGN AND METHODS: The National Lung Cancer Screening program, a multicenter, population-based, prospective cohort study, was analyzed. Information on risk factor exposure was collected during the baseline risk assessment. A Cox proportional hazards model was used to estimate the association between risk factors and lung cancer incidence. Age-specific 10-year cumulative risk was calculated to determine the age at which individuals with various risk factors reached the equivalent risk level as individuals aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history. RESULTS: Of the 1,031,911 participants enrolled in this study, 3,908 demonstrated lung cancer after a median follow-up of 3.8 years. We identified seven risk factors for lung cancer, including pack-years of smoking, secondhand smoke exposure, family history of lung cancer in first-degree relatives, history of respiratory diseases, occupational hazardous exposure, BMI, and diabetes. The 10-year cumulative risk of lung cancer for people aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history was 1.37%, which was treated as the risk threshold for screening. Individuals who never smoked and those with active tobacco use and a < 30-pack-year history of smoking reached the equivalent risk level 1 to 14 years later compared with the starting age of 50 years. Men with active tobacco use, a ≥ 30-pack-year history of smoking, and concurrent respiratory diseases or diabetes should be screened 1 year earlier at the age of 49 years. INTERPRETATION: The personalized risk-adapted starting ages for lung cancer screening, based on the principle of equal management of equal risk, can served as an optimized screening strategy to identify high-risk individuals.

Physical activity domains and patterns with risk of depressive symptoms: A cross-sectional study in China.

BACKGROUND: The health benefits of domain-specific physical activity (PA) on depressive symptoms were inconclusive. Few studies explored PA patterns and depressive symptoms. This study aimed to investigate the associations of PA domains and patterns with depressive symptoms. METHODS: We conducted a cross-sectional study in China with 5047 adults. Latent class analysis was applied to identify the PA patterns and logistic regression analysis was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: The ORs (95 % CIs) for the active versus inactive groups were 0.79 (0.69-0.91) for leisure-time PA, 0.57 (0.49-0.65) for transport PA, 0.95 (0.82-1.09) for household PA, and 1.38 (1.18-1.62) for occupational PA. We found non-linear associations between leisure-time PA, transport PA and depressive symptoms, with the lowest risk at 11 METs-h/week of leisure-time PA (equal to 147 min/week moderate PA or 88 min/week vigorous PA) and 23 METs-h/week of transport PA. There was a marginal inverse association with household PA for men while not for women. We identified four PA patterns and found a lower risk of depressive symptoms associated with "low occupational PA pattern" versus "moderate PA level pattern" (0.45 (0.38-0.52)). LIMITATIONS: Given the cross-sectional design, causality cannot be inferred. CONCLUSIONS: Our study supported an inverse association of leisure-time PA and transport PA with depressive symptoms and a positive association of occupational PA. The observed inconsistent association of household PA among men and women, and the finding that "low occupational PA pattern" was associated with a lower risk of depressive symptoms warrant further investigation.

Modifiable risk-attributable and age-related burden of lung cancer in China, 1990-2019.

BACKGROUND: There were limited studies on the quantification of the modifiable and nonmodifiable lung cancer burden over time in China. Furthermore, the potential effect of risk factor reduction for lung cancer on gains in life expectancy (LE) remains unknown. METHODS: This study explored temporal trends in lung cancer deaths and disability-adjusted life years (DALY) attributable to modifiable risk factors from 1990 to 2019, based on the 2019 Global Burden of Disease Study. The abridged period life table method was used to quantify the effect of risk factors on LE. The authors used the decomposition approach to estimate contributions of aging metrics to change in the lung cancer burden. RESULTS: Nationally, the majority of lung cancer deaths and DALYs were attributable to behavioral and environmental risk clusters. Potential gains in life expectancy (PGLE) at birth would be 0.78 years for males and 0.35 years for females if the exposure to risk factors was mitigated to the theoretical minimum level. Tobacco use had the most robust impact on LE for both sexes (PGLE: 0.71 years for males and 0.19 years for females). From 1990 to 2019, risk-attributable age-standardized death and DALY rates of lung cancer showed an increasing trend in both sexes; adult population growth imposed 245.9 thousand deaths and 6.2 million DALYs for lung cancer. CONCLUSIONS: The modifiable risk-attributable lung cancer burden remains high in China. Effective tobacco control is the critical step toward addressing the lung cancer burden. Adult population growth was the foremost driver of transition in the age-related lung cancer burden. PLAIN LANGUAGE SUMMARY: We estimate the lung cancer burden attributable to modifiable and nonmodifiable contributors and the effect of risk factor reduction for lung cancer on the life expectancy in China. The findings suggest that the majority of lung cancer deaths and disability-adjusted life years were attributable to behavioral risk clusters, and the risk-attributable lung cancer burden increased nationally from 1990 to 2019. The average gains in life expectancy would be 0.78 years for males and 0.35 years for females if the exposure to risk factors for lung cancer was reduced to the theoretical minimum risk exposure level. Adult population growth was identified as the foremost driver of variation in the aging lung cancer burden.

Esophageal cancer: Epidemiology, risk factors and screening.

More than 600,000 people are diagnosed with esophageal cancer (EC) every year globally, and the five-year survival rate of EC is less than 20%. Two common histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have great geographical variations in incidence rates. About half of the world's EC was diagnosed in China and a majority of which belong to ESCC. Globally, the overall incidence rate of EC is decreasing. In some high-risk Asian regions, such as China, the incidence rate of ESCC has generally declined, potentially due to economic growth and improvement of diet habits. In some European high-income countries and the United States, the decline is mainly attributed to the decrease in smoking and drinking. The risk factors of EC are not well understood, and the importance of environmental and genetic factors in the pathogenesis is also unclear. The incidence and mortality of advanced EC can be reduced through early diagnosis and screening. White light endoscopy is still the gold standard in the current screening technology. This article reviews the epidemiology, risk factors, and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.

Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma.

The pattern-recognition pathway plays an important role in infection recognition and immune responses, and previous studies have suggested an association between genetic variation in innate immunity genes and non-Hodgkin lymphoma (NHL). We evaluated NHL risk associated with genetic variation in pattern-recognition genes using data from a case-control study of NHL conducted in Connecticut women. Single nucleotide polymorphisms (SNPs) in 27 pattern-recognition genes were genotyped in 432 Caucasian incident NHL cases and 494 frequency-matched controls. Unconditional logistic regression was used to compute odds ratios (ORs) for NHL and common NHL subtypes in relation to individual SNPs and haplotypes. A gene-based analysis that adjusted for the number of tagSNPs genotyped in each gene showed a significant association with overall NHL for the MBP gene (P = 0.028), with the diffuse large B-cell lymphoma (DLBCL) subtype for the MASP2 gene (P = 0.011), and with the follicular lymphoma (FL) subtype for DEFB126 (P = 0.041). A SNP-based analysis showed that MBP rs8094402 was associated with decreased risks of overall NHL (allele risk OR = 0.72, P-trend = 0.0018), DLBCL (allele risk OR = 0.72, P-trend = 0.036), and FL (allele risk OR = 0.67, P-trend = 0.021), while MASP2 rs12711521 was associated with a decreased risk of DLBCL (allele risk OR = 0.57, P-trend = 0.0042). We also observed an increased risk of FL for DEFB126 rs6054706 (allele risk OR = 1.39, P-trend = 0.033). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NHL or specific NHL subtypes, but these preliminary findings require replication in larger studies.

Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma.

The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR)(CT) = 0.60, 95% confidence interval (CI) = 0.42-0.87, P(trend) = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR(CT) = 0.39, 95% CI = 0.20-0.73; P(trend) = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.

The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis.

Mammalian neural progenitor cells divide asymmetrically to self-renew and produce a neuron by segregating cytosolic Numb proteins primarily to one daughter cell. Numb signaling specifies progenitor over neuronal fates but, paradoxically, also promotes neuronal differentiation. Here we report that ACBD3 is a Numb partner in cell-fate specification. ACBD3 and Numb proteins interact through an essential Numb domain, and the respective loss- and gain-of-function mutant mice share phenotypic similarities. Interestingly, ACBD3 associates with the Golgi apparatus in neurons and interphase progenitor cells but becomes cytosolic after Golgi fragmentation during mitosis, when Numb activity is needed to distinguish the two daughter cells. Accordingly, cytosolic ACBD3 can act synergistically with Numb to specify cell fates, and its continuing presence during the progenitor cell cycle inhibits neuron production. We propose that Golgi fragmentation and reconstitution during cell cycle differentially regulate Numb signaling through changes in ACBD3 subcellular distribution and represent a mechanism for coupling cell-fate specification and cell-cycle progression.

Ultraviolet radiation exposure and risk of non-Hodgkin's lymphoma.

Sun exposure has been suggested to increase the risk of non-Hodgkin's lymphoma. The authors analyzed data from a population-based, case-control study of Connecticut women between 1996 and 2000 to study the hypothesis. Women who reported having had a suntan experienced an increased risk of non-Hodgkin's lymphoma with increasing duration (p(trend) = 0.0062) compared with women who reported never having had a suntan. An almost threefold increased risk of non-Hodgkin's lymphoma was observed among women who reported having had a suntan for less than 3 months per year and a suntan history of more than 60 years (odds ratio = 2.8, 95% confidence interval: 1.6, 4.9) compared with those who reported never having had a suntan. For women who reported having spent time in strong sunlight between 9 a.m. and 3 p.m. during the summer, a 70% increased risk of non-Hodgkin's lymphoma was observed for the highest tertile of duration compared with the lowest (odds ratio = 1.7, 95% confidence interval: 1.2, 2.4). The risk increased with increasing duration of time spent in strong sunlight in summer (p(trend) = 0.0051). The risk appears to vary by non-Hodgkin's lymphoma subtypes. Further investigations of the role of ultraviolet radiation on the risk of non-Hodgkin's lymphoma are warranted.

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut.

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case-control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P=0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P=0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56-0.91; P=0.007) and DLBCL (OR: 0.66; 95% CI: 0.45-0.95; P=0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.

The enigma of the numb-Notch relationship during mammalian embryogenesis.

Asymmetric cell division is an attractive means to diversify cell fates during development and for stem cells to balance self-renewal and differentiation. In Drosophila, two signaling pathways, one mediated by Numb and the other by Notch, play essential but antagonistic roles in enabling the two daughters to adopt different fates after a wide variety of asymmetric cell divisions. However, recent studies show that mutating mammalian Numb homologues, m-Numb and Numblike (Numbl or Nbl), and eliminating Notch signaling in the developing nervous system both lead to premature depletion of neural stem/progenitor cells in mice. These findings raise an interesting question as to whether and how the antagonistic roles of Numb and Notch signaling are conserved in vertebrates. Here we provide evidence that loss of m-Numb and Numbl outside the embryonic nervous system also causes phenotypes similar to those exhibited by mice with defective Notch signaling. We further show that very little Numb protein is necessary for embryogenesis and that the presence of different m-Numb isoforms is unlikely to provide a molecular basis for differential regulation of Notch signaling in mammals, as these isoforms are functionally indistinguishable in cell fate specification. We discuss possible mechanisms by which the antagonistic roles of Numb and Notch are evolutionarily conserved to meet the needs of stem cell maintenance during mammalian neurogenesis.

Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.

Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.

A putative exonic splicing polymorphism in the BCL6 gene and the risk of non-Hodgkin lymphoma.

Recent studies have shown that the B-cell lymphoma 6 gene (BCL6) is an oncogene that contributes to lymphomagenesis. Exon 6 of BCL6 contains a common single nucleotide polymorphism (SNP) (-195 C>T; dbSNP ID: rs1056932) that alters a potential binding site for an exonic splicing enhancer. We used unconditional logistic regression models to examine the association between this SNP and the risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study of women residing in Connecticut (461 case patients and 535 control subjects). The risk of NHL among women with the CC genotype was more than double that of women with the TT genotype (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.5 to 3.3). Higher risks were observed for two NHL subtypes, namely B-cell chronic lymphatic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma (OR = 3.5, 95% CI = 1.6 to 7.8) and T-cell lymphoma (OR = 5.2, 95% CI = 2.0 to 13.3). Our results support the hypothesis that a genetic variant that could alter mRNA transcripts of BCL6 may contribute to the etiology of NHL and suggest that this variant warrants further investigation.

Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of breast cancer in Connecticut women.

Recent epidemiologic studies have suggested that genetic polymorphisms in the cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors report results from a case-control study evaluating the potential effect of gene-environment interaction between CYP1A1 and serum PCB levels on breast cancer risk among Caucasian women in Connecticut. The study included 374 case women with histologically confirmed breast cancer and 406 noncancerous controls with information on both serum PCB level and CYP1A1 genotype (1999-2002). Compared with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 variant genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9), especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI: 1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher serum PCB levels (611-2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not associated with breast cancer risk independently or in combination with PCB exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer and may modify the relation between PCB exposure and breast cancer risk.

Menstrual and reproductive factors and risk of non-Hodgkin's lymphoma among Connecticut women.

Several recent studies have suggested a potential role of menstrual and reproductive factors in the risk of non-Hodgkin's lymphoma. To further examine the relation, the authors analyzed data from a population-based case-control study of non-Hodgkin's lymphoma in Connecticut women between 1996 and 2000. A total of 601 histologically confirmed cases and 717 randomly selected population-based controls were included in this study. An in-person interview was conducted using a standardized and structured questionnaire to collect information on menstrual and reproductive factors and potential confounding factors. Compared with nulliparous women, women who had four or more pregnancies during their lifetime were found to have a significantly reduced risk of non-Hodgkin's lymphoma (odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.4, 0.9). Risk appeared to decrease with increasing number of pregnancies (p(trend) = 0.03). The authors also observed an increased risk of non-Hodgkin's lymphoma overall (OR = 1.5, 95% CI: 1.0, 2.2) and of diffuse non-Hodgkin's lymphoma (OR = 1.7, 95% CI: 1.1, 2.7) for women who started their first menstrual period at age 15 or more years compared with those who started their first menstrual period before age 12 years. These findings support a reduced risk of non-Hodgkin's lymphoma associated with multiple pregnancies and an increased risk of non-Hodgkin's lymphoma associated with later age at menarche.

Blood transfusion and risk of non-Hodgkin's lymphoma in Connecticut women.

The incidence and mortality rates of non-Hodgkin's lymphoma have been increasing worldwide. Allogeneic blood transfusion has been suggested as a risk factor for non-Hodgkin's lymphoma, but the results from epidemiologic studies have been inconsistent. Data from a population-based case-control study of Connecticut women were analyzed to evaluate this relation. A total of 601 histologically confirmed, non-Hodgkin's lymphoma incident cases identified between 1996 and 2000 and 717 randomly selected controls were included in this study. Allogeneic blood transfusion was not associated with the increased risk of non-Hodgkin's lymphoma overall (odds ratio = 1.0, 95% confidence interval: 0.7, 1.3) or by subtype of the disease. The risk also did not vary by number of allogeneic blood transfusions, age at first transfusion, or time since first transfusion. When the reason for blood transfusion was considered, an increased risk of non-Hodgkin's lymphoma was found only for allogeneic blood transfusion for reason of anemia. In summary, the authors' findings do not support the hypothesis that allogeneic blood transfusion increases the risk of non-Hodgkin's lymphoma.

Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis.

Neural progenitor cells in the developing neocortex change over time to produce different neurons, a phenomenon that is also observed in other regions of the nervous system. Mouse Numb (also known as m-numb) and Numbl (also known as numblike or Nbl) are redundant but essential in maintaining virtually all progenitor cells during early neurogenesis. They do this by allowing cells to choose progenitor over neuronal fates. To determine whether their roles change as neurogenesis progresses, we conditionally ablated both genes in the embryonic dorsal forebrain after initial waves of neurogenesis. Here we report that these proteins continue to be required for progenitor-cell maintenance, contrary to recently reported findings. As occurs during early neurogenesis, the loss of Numb and Numbl causes premature progenitor-cell depletion and, consequently, a highly specific malformation of the neocortex and hippocampus. Because progenitor cells can proliferate without Numb and Numbl before neurogenesis, we propose that Numb-mediated asymmetric cell divisions, which diversify many cell fates in Drosophila melanogaster, represent a general mechanism in mammals for stem cells to balance self-renewal and differentiation.

Major molecular differences between mammalian sexes are involved in drug metabolism and renal function.

Many anatomical differences exist between males and females; these are manifested on a molecular level by different hormonal environments. Although several molecular differences in adult tissues have been identified, a comprehensive investigation of the gene expression differences between males and females has not been performed. We surveyed the expression patterns of 13,977 mouse genes in male and female hypothalamus, kidney, liver, and reproductive tissues. Extensive differential gene expression was observed not only in the reproductive tissues, but also in the kidney and liver. The differentially expressed genes are involved in drug and steroid metabolism, osmotic regulation, or as yet unresolved cellular roles. In contrast, very few molecular differences were observed between the male and female hypothalamus in both mice and humans. We conclude that there are persistent differences in gene expression between adult males and females. These molecular differences have important implications for the physiological differences between males and females.

Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women.

OBJECTIVE: To further investigate the role of prior medical conditions and medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the data from a population-based case-control study of NHL in Connecticut women. METHODS: A total of 601 histologically confirmed incident cases of NHL and 717 population-based controls were included in this study. In-person interviews were administered using standardized, structured questionnaires to collect information on medical conditions and medication use. RESULTS: An increased risk was found among women who had a history of autoimmune disorders (such as rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, and multiple sclerosis), anemia, eczema, or psoriasis. An increased risk was also observed among women who had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was found for women who had scarlet fever or who had used estrogen replacement therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with past medical history appeared to vary based on NHL subtypes, but the results were based on small number of exposed subjects. CONCLUSION: A relationship between certain prior medical conditions and medication use and risk of NHL was observed in this study. Further studies are warranted to confirm our findings.

Progenitor cell maintenance requires numb and numblike during mouse neurogenesis.

Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities.