A Genome Wide Meta-Analysis Study for Identification of Common Variation Associated with Breast Cancer Prognosis

Objective

Genome wide association studies (GWAs) of breast cancer mortality have identified few potential associations. The concordance between these studies is unclear. In this study, we used a meta-analysis of two prognostic GWAs and a replication cohort to identify the strongest associations and to evaluate the loci suggested in previous studies. We attempt to identify those SNPs which could impact overall survival irrespective of the age of onset.

Methods

To facilitate the meta-analysis and to refine the association signals, SNPs were imputed using data from the 1000 genomes project. Cox-proportional hazard models were used to estimate hazard ratios (HR) in 536 patients from the POSH cohort (Prospective study of Outcomes in Sporadic versus Hereditary breast cancer) and 805 patients from the HEBCS cohort (Helsinki Breast Cancer Study). These hazard ratios were combined using a Mantel-Haenszel fixed effects meta-analysis and a p-value threshold of 5×10⁻⁸ was used to determine significance. Replication was performed in 1523 additional patients from the POSH study.

Results

Although no SNPs achieved genome wide significance, three SNPs have significant association in the replication cohort and combined p-values less than 5.6×10⁻⁶. These SNPs are; rs421379 which is 556 kb upstream of ARRDC3 (HR = 1.49, 95% confidence interval (CI) = 1.27–1.75, P = 1.1×10⁻⁶), rs12358475 which is between ECHDC3 and PROSER2 (HR = 0.75, CI = 0.67–0.85, P = 1.8×10⁻⁶), and rs1728400 which is between LINC00917 and FOXF1.

Conclusions

In a genome wide meta-analysis of two independent cohorts from UK and Finland, we identified potential associations at three distinct loci. Phenotypic heterogeneity and relatively small sample sizes may explain the lack of genome wide significant findings. However, the replication at three SNPs in the validation cohort shows promise for future studies in larger cohorts. We did not find strong evidence for concordance between the few associations highlighted by previous GWAs of breast cancer survival and this study.     

Life Satisfaction and Morbidity among Postmenopausal Women

Objective

To investigate associations between morbidity and global life satisfaction in postmenopausal women taking into account type and number of diseases.

Materials and Methods

A total of 11,084 women (age range 57–66 years) from a population-based cohort of Finnish women (OSTPRE Study) responded to a postal enquiry in 1999. Life satisfaction was measured with a 4-item scale. Self-reported diseases diagnosed by a physician and categorized according to ICD-10 main classes were used as a measure of morbidity. Enquiry data on health and lifestyle were used as covariates in the multivariate logistic models.

Results

Morbidity was strongly associated with life dissatisfaction. Every additional disease increased the risk of life dissatisfaction by 21.1% (p < .001). The risk of dissatisfaction was strongest among women with mental disorders (OR = 5.26; 95%CI 3.84–7.20) and neurological disorders (OR = 3.62; 95%CI 2.60–5.02) compared to the healthy (each p < .001). Smoking, physical inactivity and marital status were also associated with life dissatisfaction (each p < .001) but their introduction to the multivariate model did not attenuate the pattern of associations.

Conclusions

Morbidity and life dissatisfaction have a disease-specific and dose-dependent relationship. Even if women with mental and neurological disorders have the highest risk for life dissatisfaction, monitoring life satisfaction among aging women regardless of disorders should be undertaken in order to intervene the joint adverse effects of poor health and poor well-being.     

Change of pupal size of Panolis flammea (Lepidoptera; Noctuidae) and Bupalus piniarius (Geometridae) in response to concentration of industrial pollutants in their food plant

Summary Larvae of Panolis flammea and Bupalus piniarius were reared in the laboratory on needles of Scots pine affected by industrial air pollutants in Finland. Needles were collected at different distances from a distinctive source of emission along two 9-km-long transects, and from independent control plots. The elemental composition of the needles used as larval food was analysed. Pupal weight, length and width were negatively correlated wiht the distance from the source of emission. The elemental composition of the pine needles explained 24–53% of the variation in pupal weight. Most of the explained variation was assoicated with the concentration of heavy meals in the pine needles.     

Risk of disability and mortality due to overweight in a Finnish population.

OBJECTIVE--To investigate the effect of overweight on premature mortality and work disability in young and middle aged Finns. DESIGN--Prospective cohort study based on data collected in the multiphasic health examinations by the Social Insurance Institution of Finland from 1966 to 1972 and follow up until 1982. SETTING--34 Communities throughout Finland. SUBJECTS--12,053 Women and 19,076 men who were employed and aged 25-64 at baseline. MAIN OUTCOME MEASURES--Mortality and work disability pensions from all and specified causes. RESULTS--Body mass index was a weak predictor of death but a strong predictor of early work disability, which increased linearly with body mass index. After adjustment for age, geographical region, occupation, and smoking the relative risks of work disability for women and men with a body mass index greater than or equal to 30 kg/m2 were, respectively, 2.0 (95% confidence interval 1.8 to 2.3) and 1.5 (1.3 to 1.7) when compared with those of subjects with body mass index less than 22.5 kg/m2. The increased risks were due to an excess of cardiovascular and musculoskeletal diseases but not of mental diseases. One fourth of all disability pensions from cardiovascular and musculoskeletal causes in women and half as many in men could be attributed to overweight (body mass index greater than 25 kg/m2) alone. CONCLUSIONS--Though modest overweight has little impact on mortality it predicts severe functional impairment. A considerable proportion of work disability pensions could probably be prevented by efficient weight control.     

重庆市蝴蝶多样性环境健康指示作用和环境监测评价体系构建

在重庆市生态功能区蝴蝶多样性参数研究的基础上,进行区系相似性分析;选取22个蝴蝶多样性参数和5项主要环境因子指标,进行回归和主成分分析,进而探讨监测指标、监测种类和类群的选取与评价体系的建立。分析结果表明:当进行区域级的监测时,在22个指标中,种、科、属的多样性指数和均匀度指数可以忽略;5项环境指标中,人口压力(X22)因子重于面积比例(X18)、人口密度(X19)、林地比例(X20)、土地载有量(X21)等4项因子。选出物种数(X1),蝴蝶属(X2)、科级(X3)单元的多少,种类优势度(X9),各数量等级的物种数贡献率(X10—X13),人口压力(X22)及4个主成分的综合得分等10个因子,作为重庆市生态功能区环境健康状况的10个评价指标;和24个蝴蝶监测种类,12个蝴蝶监测类群一起,探讨评价方法,共同构筑了重庆市生态功能区环境监测评价体系。在此基础上,对各功能区环境健康状况的评价表明,功能区1的环境健康评价为非常健康,5、9、10区为健康功能区;2、3、6、7、14区为亚健康功能区;不健康功能区是4、8、11、12、13区。功能区13、14是城市化区域,它们的分值在14个区中,居第十二位和第七位,不是最低的,这表明城镇化与环境质量并不完全是因果关系,即通过绿化和环境保护,城镇环境是可能得到很好改善的。期望此监测评价体系在实践中进一步完善。     

Annual and seasonal variation of sap flow and conductance of pine trees grown in elevated carbon dioxide and temperature

Measurements of sap flow, crown structure, and microclimate were used to estimate the transpiration of individual 30-year-old Pinus sylvestris L. trees grown in elevated temperature and CO2. The trees were enclosed in closed-top chambers and exposed either to current ambient conditions (CON), or elevated CO2 (+350 micromol mol(-1); EC), or elevated temperature (+2 to +6 degrees C; ET) or a combination of EC and ET (ECT) since 1996, and the measurements were made from 1999 to 2001. EC significantly increased annual sap flow per tree (Ft.m) by 14% in 1999, but reduced it by 13% in 2000 and 16% in 2001. The CO2-induced increase in Ft.m in 1999 was due to a large increase in foliage area of trees, which more than compensated for a small decrease in crown conductance (Gc). The CO2-induced decreases in Ft.m in 2000 and 2001 resulted from a pronounced decline in Gc, which was much greater than the increase in foliage area. The CO2-induced increase in sensitivity of Gc at high vapour pressure deficit (VPD) did not alter the general response of sap flow to CO2 enrichment, but it did affect the diurnal courses of sap flow on some days during the main growing season (days 150-240). ET increased Ft.m by 53%, 45%, and 57% in 1999, 2000, and 2001, respectively, attributable to the combined effects of greater foliage area and maximum crown conductance, lower stomatal sensitivity to high VPD, and higher transpiration demand relative to the control treatments. There was no significant interaction between CO2 and temperature on sap flow, because ECT entailed approximately similar patterns of sap flow to ET, suggesting that the temperature played a dominate role in the case of ECT under boreal climate conditions.     

沙棘木蠹蛾蛹的空间分布

沙棘木蠹蛾（Holcocerus hippophaecolus Hua, Chou , Fang et Chen）是近几年在内蒙古、辽宁、山西、宁夏和陕西等地大面积爆发的一种钻蛀性害虫,该虫约4a完成1代,主要以幼虫危害沙棘（Hippophae rhamnoidea）的根部和干部,老熟幼虫在土壤中化蛹.为了解种群的空间结构,从而有效控制其危害,应用生物学统计方法和地质统计学（Geostatistics）方法对沙棘木蠹蛾蛹的空间分布特性进行了分析研究.结果表明：约90%的蛹在6月初到7月末之间羽化,而7月份羽化的数量占总数的一半之多.在调查样地中,雌雄蛹的比例基本为1：1.每株沙棘树周围,蛹的数量为0～4个,有蛹株率仅为24.3%.蛹在距离根基部周围1.3m的范围内均有分布,不同分布区间内蛹的数量变化没有一定的规律性,但90%的蛹分布在距根基部1m的范围内.沙棘木蠹蛾蛹的种群呈现较明显的空间聚集状态,空间依赖范围大小为11.1m,局部空间连续性强度为90.7%,呈现较明显的斑块状分布,在整个区域内有很多聚集点.对不同样方大小的变异曲线图进行比较得知：样方边长分别为5、6、7m时,变程、空间局部连续性强度和基台值的变化幅度均很小,几乎相等,而样方边长为5m时的决定系数较大,此样方为最适样方大小.     

不同配置模式林分中光肩星天牛空间格局的地统计研究

运用地统计学方法对光肩星天牛在新疆杨和复叶槭混交林（新复混交林）、合作杨纯林以及新疆杨与合作杨混交林（新合混交林）3种林分中的空间格局进行了研究.结果表明：刻槽、排粪孔和羽化孔在新复混交林和合作杨纯林中呈现较明显的空间聚集状态,而在新合混交林中则呈现完全的随机分布.新复混交林中,刻槽和排粪孔在林内的扩散趋势完全相反,即刻槽由林地周围向中心扩散,而排粪孔则由林地中心向四周扩散,这在一定程度上反映了光肩星天牛喜好产卵于刻槽较少,危害较轻的树上,而羽化孔在新复混交林中的分布数量较少,仅有几处聚集分布,由这些零星分布的聚集斑块向周围扩散;合作杨纯林中,由于林缘通风透光,合作杨生长状况较好,受害严重,从而导致枯死,最终失去对光肩星天牛的诱集作用,光肩星天牛刻槽、排粪孔和羽化孔由林地周围向中心扩散;而新合混交林中,刻槽、排粪孔和羽化孔在林内有多个聚集区域,并以此为中心向四周扩散,保持聚集和扩散平衡状态,从而表现为随机分布,这主要是由林内树种的配置情况所决定的.就不同配置树种的空间依赖性范围而言,刻槽和羽化孔在新复混交林内的空间依赖性范围要远远大于合作杨纯林,而排粪孔则远小于合作杨;就样方内的空间连续性强度而言,新复混交林中刻槽大于合作杨纯林,而排粪孔和羽化孔均小于合作杨纯林,这些均说明光肩星天牛危害在新复混交林内较集中,而在合作杨纯林内较分散.