Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers

Abstract Introduction Women who carry mutations in BRCA1 and BRCA2 have a substantially increased risk of developing breast cancer as compared with the general population. However, risk estimates range from 20 to 80%, suggesting the presence of genetic and/or environmental risk modifiers. Based on extensive in vivo and in vitro studies, one important pathway for breast cancer pathogenesis may be the insulin-like growth factor (IGF) signaling pathway, which regulates both cellular proliferation and apoptosis. BRCA1 has been shown to directly interact with IGF signaling such that variants in this pathway may modify risk of cancer in women carrying BRCA mutations. In this study, we investigate the association of variants in genes involved in IGF signaling and risk of breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations. Methods A cohort of 1,665 adult, female mutation carriers, including 1,122 BRCA1 carriers (433 cases) and 543 BRCA2 carriers (238 cases) were genotyped for SNPs in IGF1, IGF1 receptor (IGF1R), IGF1 binding protein (IGFBP1, IGFBP2, IGFBP5), and IGF receptor substrate 1 (IRS1). Cox proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was assumed; and for single SNP analyses, no additivity assumptions were made. Results Among BRCA1 carriers, significant associations were found between risk of breast cancer and LD blocks in IGF1R (global P = 0.011 for LD block 2 and global P = 0.012 for LD block 11). Among BRCA2 carriers, an LD block in IGFBP2 (global P = 0.0145) was found to be associated with the time to breast cancer diagnosis. No significant LD block associations were found for the other investigated genes among BRCA1 and BRCA2 carriers. Conclusions This is the first study to investigate the role of genetic variation in IGF signaling and breast cancer risk in women carrying deleterious mutations in BRCA1 and BRCA2. We identified significant associations in variants in IGF1R and IRS1 in BRCA1 carriers and in IGFBP2 in BRCA2 carriers. Although there is known to be interaction of BRCA1 and IGF signaling, further replication and identification of causal mechanisms are needed to better understand these associations

Scientific Productivity of Saudi Faculty Members at Umm Alqura University: Its Status and Obstacles

Goals: Determining the average amount of research produced by a faculty member annually, and identifying the major obstacles of their research productivity. Data collection: A questioner distributed to the population of 244 Saudi faculty members, and when responses had reached 60 percent of the population, data was statistically analyzed. Findings: The major findings concerning research productivity include: faculty members produced an average of 0.4 research units per year. This average is less than the productivity level of their peers at advanced countries' universities , the average is 1-2 research units, . About 38.4% of faculty members have failed to produce any research since their graduation. Pay increases and promotions have ceased for about 63% of the assistant professors and 83% of associate professors because they failed to produce the required amount of research for their promotion. About 60% of faculty members are not satisfied with their research productivity because they produced less research than expected. There is a positive correlation of 0.5 between high productivity and faculty years of experience. Obstacles inhibiting scientific productivity have many sources. Faculty members think most of these obstacles are due to their institution. Obstacles related to the institution include scarce conferences and scientific meetings, few chances to attend such conferences abroad, poor library facilities with few up-to-date books and specialized periodicals, insufficient research equipment and facilities, unavailability of research assistants and support staff, low encouragement and motivation to researchers, low priority and limited funds allocated to research, overlong administrative procedures for processing research approval for publishing, limited channels for publishing faculty members' works inside their university. overloaded teaching schedule due to shortages of teaching staff, heavy engagement in administrative duties, poor research atmosphere and infirm research tradition. Social obstacles to research as reported by faculty members include: limited research support by private sector, low social priority and demand on research because society docs not believe strongly in its visible and applicative reality. Some of the individual obstacles reported are that faculty members think doing research at their expense is not profitable seeing that they have to spend a considerable sum of money in order to publish it

Scientific Productivity of Saudi Faculty Members at Umm Alqura University: Its Status and Obstacles

Goals: Determining the average amount of research produced by a faculty member annually, and identifying the major obstacles of their research productivity. Data collection: A questioner distributed to the population of 244 Saudi faculty members, and when responses had reached 60 percent of the population, data was statistically analyzed. Findings: The major findings concerning research productivity include: faculty members produced an average of 0.4 research units per year. This average is less than the productivity level of their peers at advanced countries' universities , the average is 1-2 research units, . About 38.4% of faculty members have failed to produce any research since their graduation. Pay increases and promotions have ceased for about 63% of the assistant professors and 83% of associate professors because they failed to produce the required amount of research for their promotion. About 60% of faculty members are not satisfied with their research productivity because they produced less research than expected. There is a positive correlation of 0.5 between high productivity and faculty years of experience. Obstacles inhibiting scientific productivity have many sources. Faculty members think most of these obstacles are due to their institution. Obstacles related to the institution include scarce conferences and scientific meetings, few chances to attend such conferences abroad, poor library facilities with few up-to-date books and specialized periodicals, insufficient research equipment and facilities, unavailability of research assistants and support staff, low encouragement and motivation to researchers, low priority and limited funds allocated to research, overlong administrative procedures for processing research approval for publishing, limited channels for publishing faculty members' works inside their university. overloaded teaching schedule due to shortages of teaching staff, heavy engagement in administrative duties, poor research atmosphere and infirm research tradition. Social obstacles to research as reported by faculty members include: limited research support by private sector, low social priority and demand on research because society docs not believe strongly in its visible and applicative reality. Some of the individual obstacles reported are that faculty members think doing research at their expense is not profitable seeing that they have to spend a considerable sum of money in order to publish it

An analysis of the competencies needed by extension workers in the southern province of Saudi Arabia

The main objectives of this study were: 1) to identify the main characteristics of extension work-ers;2) to determine the competencies needed pertaining to six areas of the extension work, i.e. philosophy. organization and administration of extension; teaching and learning process; human develop-ment and social knowledge, communication; program planning and development, research and evalua-tion;3) to identify the nature of the relationship between extension workers, characteristics and their needs for additional training. The empirical inquiry covered 114 extension workers representing the total extension workers in the Southern Province. The data were collected by means of personal interview. The results of the study revealed that: 1) most of extension workers were relatively young, unspecialized in extension; 2) the extension workers needed training in all the studied areas particularly in the following areas: research and evaluation in extension; teaching and learning process. There were significant relationships between some of the extension workers' characteristics and their need for train-ing. Among the important recommendations of the study are: the urgent need to establish agricultural extension specialization in the College of Agriculture in the Kingdom, and to plan and implement a training program to raise the competencies of the extension workers

Cross-border movement, economic development and malaria elimination in the Kingdom of Saudi Arabia

Malaria at international borders presents particular challenges with regards to elimination. International borders share common malaria ecologies, yet neighboring countries are often at different stages of the control-to-elimination pathway. Herein, we present a case study on malaria, and its control, at the border between Saudi Arabia and Yemen. Malaria program activity reports, case data, and ancillary information have been assembled from national health information systems, archives, and other related sources. Information was analyzed as a semi-quantitative time series, between 2000 and 2017, to provide a plausibility framework to understand the possible contributions of factors related to control activities, conflict, economic development, migration, and climate. The malaria recession in the Yemeni border regions of Saudi Arabia is a likely consequence of multiple, coincidental factors, including scaled elimination activities, cross-border vector control, periods of low rainfall, and economic development. The temporal alignment of many of these factors suggests that economic development may have changed the receptivity to the extent that it mitigated against surges in vulnerability posed by imported malaria from its endemic neighbor Yemen. In many border areas of the world, malaria is likely to be sustained through a complex congruence of factors, including poverty, conflict, and migration