Prevalence and Genotype-Phenotype Correlation of Lynch Syndrome in a Selected High-Risk Cohort from Qatar's Population.

Lynch syndrome (LS) is the most common cause of hereditary colorectal cancers (CRC) and is associated with an increased risk for ovarian and endometrial cancers. There is lack of knowledge on the epidemiology of LS in the non-Caucasian populations especially in Qatar. The aim of this retrospective study is to explore the prevalence of LS in a selected high-risk cohort in the State of Qatar in addition to investigating the frequency and genotype-phenotype correlation associated with mismatch repair genes pathogenic variants. Retrospective review of medical records of 31 individuals with LS, 20 affected with colorectal cancer and 11 unaffected with family history of cancers, referred from January 2017 until August 2020. The prevalence of LS among affected and unaffected patients is 22% (20/92) and 2.2% respectively. Among affected individuals, MLH1 and MSH2 genes were highly frequent while for unaffected individuals, a recurrent PMS2 pathogenic variant was reported in several related individuals suggesting a tribal effect. This study highlights the epidemiology of LS in high-risk cohort in Qatar which helps to provide recommendations on genetic testing, and personalize surveillance and management programs.

Immune-related 3-lncRNA signature with prognostic connotation in a multi-cancer setting.

BACKGROUND: Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding. METHODS: We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets. RESULTS: Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR. CONCLUSION: We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.

Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry.

Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E - 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.

Metabolic Signatures of Tumor Responses to Doxorubicin Elucidated by Metabolic Profiling in Ovo.

BACKGROUND: Dysregulated cancer metabolism is associated with acquired resistance to chemotherapeutic treatment and contributes to the activation of cancer survival mechanisms. However, which metabolic pathways are activated following treatment often remains elusive. The combination of chicken embryo tumor models (in ovo) with metabolomics phenotyping could offer a robust platform for drug testing. Here, we assess the potential of this approach in the treatment of an in ovo triple negative breast cancer with doxorubicin. METHODS: MB-MDA-231 cells were grafted in ovo. The resulting tumors were then treated with doxorubicin or dimethyl sulfoxide (DMSO) for six days. Tumors were collected and analyzed using a global untargeted metabolomics and comprehensive lipidomics. RESULTS: We observed a significant suppression of tumor growth in the doxorubicin treated group. The metabolic profiles of doxorubicin and DMSO-treated tumors were clearly separated in a principle component analysis. Inhibition of glycolysis, nucleotide synthesis, and glycerophospholipid metabolism appear to be triggered by doxorubicin treatment, which could explain the observed suppressed tumor growth. In addition, metabolic cancer survival mechanisms could be supported by an acceleration of antioxidative pathways. CONCLUSIONS: Metabolomics in combination with in ovo tumor models provide a robust platform for drug testing to reveal tumor specific treatment targets such as the antioxidative tumor capacity.

Cancer genetics program: Follow-up on clinical genetics and genomic medicine in Qatar.

This article presents an overview of the cancer genetics program in Qatar. In addition to summarizing clinical, research, educational, and other aspects, data related to testing outcomes (over the course of approximately 5.5 years) are presented.

Perceptions of Arab men regarding female breast cancer screening examinations-Findings from a Middle East study.

OBJECTIVES: In the Middle East, Qatar in particular, the incidence of breast cancer has substantially increased in recent years, and is expected to double by 2030. This diagnosis also occurs at a later stage in the disease. Early detection along with proper treatment reduces radical mastectomy and mortality rates, yet only one-third of Arab women in Qatar participate in breast cancer screening (BCS) activities of any sort. Many women in the conservative Qatari society rely on male family members for support and protection. This study investigates the attitudes and perceptions of Arab men in regards to breast cancer screening and what they see as both incentives and barriers to women's participation in BCS activities. DESIGN: A qualitative methodology using purposive sampling technique was chosen in order to explore participant's attitudes, beliefs and health-related actions. Individual in-depth interviews with open-ended questions were conducted with 50 Arab men during October 2011 to May 2012. Data collection, analysis, and interpretation occurred simultaneously. NVivo 9, a qualitative data analysis software program was used to organize themes and subthemes. RESULTS: It was found that most men understood the importance of regular BCS in early detection of breast cancer. They felt they had an important role in encouraging the women in their lives to participate in BCS activities, but were adamant that any examination must be done by a female health care professional. Few knew details about screening guidelines in Qatar, but most had a basic knowledge of some screening activities. Most indicated an interest in learning more about BC and screening activities in order to better help and inform their female family members. CONCLUSION: Because Arab men perceive that their opinions and support are a major factor influencing female family members' participation in breast cancer screening, it is important that any program instituted to increase such screening participation be aimed at both men and women. More information is needed by both sexes as to the need for and benefits of regular screening activities, the techniques used, and the newly revised guidelines in Qatar. Such a program needs to be introduced in the near future in order to avert, at least partially, the expected doubling in breast cancer cases by 2030 in the Middle East.

Addressing Factors Associated with Arab Women's Socioeconomic Status May Reduce Breast Cancer Mortality: Report from a Well Resourced Middle Eastern Country.

Differences in socioeconomic status (SES) such as income levels may partly explain why breast cancer screening (BCS) disparities exist in countries where health care services are free or heavily subsidized. However, factors that contribute to such differences in SES among women living in well resourced Middle East countries are not fully understood. This quantitative study investigated factors that influence SES and BCS of Arab women. Understanding of such factors can be useful for the development of effective intervention strategies that aim to increase BCS uptake among Arab women. Using data from a cross-sectional survey among 1,063 Arabic-speaking women in Qatar, age 35+, additional data analysis was performed to determine the relationship between socioeconomic indicators such as income and other factors in relation to BCS activities. This study found that income is determined and influenced by education level, occupation, nationality, years of residence in the country, level of social activity, self-perceived health status, and living area. Financial stress, unemployment, and unfavorable social conditions may impede women's participation in BCS activities in well resourced Middle East countries.

Do socioeconomic factors influence breast cancer screening practices among Arab women in Qatar?

OBJECTIVES: Breast cancer incidence rates are rising in Qatar. Although the Qatari government provides subsidised healthcare and screening programmes that reduce cost barriers for residents, breast cancer screening (BCS) practices among women remain low. This study explores the influence of socioeconomic status on BCS among Arab women in Qatar. SETTING: A multicentre, cross-sectional quantitative survey was conducted with 1063 Arab women (87.5% response rate) in Qatar from March 2011 to July 2011. Women who were 35 years or older and had lived in Qatar for at least 10 years were recruited from seven primary healthcare centres and women's health clinics in urban and semiurban regions of Qatar. Associations between socioeconomic factors and BCS practice were estimated using χ(2) tests and multivariate logistic regression analyses. RESULTS: Findings indicate that less than one-third of the participants practised BCS appropriately, whereas less than half of the participants were familiar with recent BCS guidelines. Married women and women with higher education and income levels were significantly more likely to be aware of and to practise BCS than women who had lower education and income levels. CONCLUSIONS: Findings indicate low levels of awareness and low participation rates in BCS among Arab women in Qatar. Socioeconomic factors influence these women's participation in BCS activities. The strongest predictors for BCS practice are higher education and higher income levels. RECOMMENDATIONS: Additional research is needed to explore the impact of economic factors on healthcare seeking behaviours in the Middle Eastern countries that have a high national gross domestic product where healthcare services are free or heavily subsidised by the government; promotion of BCS and intervention strategies in these countries should focus on raising awareness about breast cancer, the cost and benefit of early screening for this disease, particularly among low-income women.

Factors that influence awareness of breast cancer screening among Arab women in Qatar: results from a cross sectional survey.

BACKGROUND: Breast cancer is the most common cancer among women in the State of Qatar. Due to low participation in breast cancer screening (BCS) activities, women in Qatar are often diagnosed with breast cancer at advanced stages of the disease. Findings indicate that low participation rates in BCS activities are significantly related to women's low level of awareness of breast cancer screening. The objectives of this study were to: (1) determine the factors that influence Qatari women's awareness of breast cancer and its screening activities: and (2) to find ways to effectively promote breast cancer screening activities among Arabic speaking women in Qatar. MATERIALS AND METHODS: A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) female Qatari citizens and non-Qatari Arabic-speaking residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Outcome measures included participant awareness levels of the most recent national recommended guidelines of BCS, participation rates in BCS activities, and factors related to awareness of BCS activities. RESULTS: While most participants (90.7%) were aware of breast cancer, less than half had awareness of BCS practices (28.9% were aware of breast self-examination and 41.8% of clinical breast exams, while 26.4% knew that mammography was recommended by national screening guidelines. Only 7.6% had knowledge of all three BCS activities). Regarding BCS practice, less than one-third practiced BCS appropriately (13.9% of participants performed breast self-examination (BSE) monthly, 31.3% had a clinical breast exam (CBE) once a year or once every two years, and 26.9% of women 40 years of age or older had a mammogram once every year or two years). Awareness of BCS was significantly related to BCS practice, education level, and receipt of information about breast cancer and/or BCS from a variety of sources, particularly doctors and the media. CONCLUSIONS: The low levels of participation rates in BCS among Arab women in this study indicate a strong need to increase awareness of the importance of breast cancer screening in Qatari women. Without this awareness, compliance with the most recent breast cancer screening recommendations in Qatar will remain low. An increased effort to implement mass media and public health campaigns regarding the impact of breast cancer on women's health and the benefits of early detection of breast cancer must be coupled with an enhanced participation of health care providers in delivering this message to Qatar population.

Beliefs and attitudes about breast cancer and screening practices among Arab women living in Qatar: a cross-sectional study.

BACKGROUND: Despite rising breast cancer incidence and mortality rates, breast cancer screening (BCS) rates among women in Qatar remain low. Previous studies indicate the need to better understand the many complex beliefs, values, and attitudes that influence Arab women's health seeking behavior for the development of culturally appropriate and effective intervention strategies to address breast cancer in the Middle East. This study investigates beliefs, attitudes, and BCS practices of Arabic-speaking women in Qatar. METHODS: A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) Arabic-speaking female Qatari citizens and non-Qatari residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Associations between beliefs and BCS practice were estimated using chi-square tests and multivariate logistic regression analyses. Participants who adhered to BCS guidelines (BCS practice = Yes) were compared to those who did not (BCS practice = No). RESULTS: In addition to low levels of awareness and low participation rates in BCS, one quarter of the participants stated their doctors talked to them about breast cancer, and less than half of the women interviewed believed breast cancer can be prevented. Women who engaged in BCS practice were more likely to have a doctor who talked to them about breast cancer, to believe they were in good-excellent health, that cancer can be prevented, or that cancer might be hereditary. The majority wanted to know if they had cancer and felt their health care needs were being met. The main reasons given for not planning BCS were lack of a doctor's recommendation, fear, and embarrassment. CONCLUSIONS: These findings indicate that a variety of channels (health care providers, media, breast cancer survivors, community leaders) should be utilized to create culturally appropriate breast cancer intervention programs and increased awareness of breast cancer, BCS, and the benefits of early detection of breast cancer. Employment of these measures will reduce breast cancer mortality rates among Arabic-speaking women living in the State of Qatar.

Arab women's breast cancer screening practices: a literature review.

Breast cancer incidence and mortality rates are increasing in the Arab world and the involved women are often diagnosed at advanced stages of breast cancer. This literature review explores factors influencing Arab women's breast cancer screening behavior. Searched databases were: Medline, PubMed, Cochrane Database of Systematic Reviews, CINAHL Plus, Google Scholar, Index Medicus for WHO Eastern Mediterranean, and Asian Pacific Journal of Cancer Prevention. Breast cancer screening participation rates are low. Screening programs are opportunistic and relatively new to the region. Knowledge amongst women and health care providers, professional recommendation, socio-demographic factors, cultural traditions, beliefs, religious, social support, accessibility and perceived effectiveness of screening influence screening behavior.