Purpose
Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by ...evaluating a broader range of risk factors.
Methods
Between 2009 and 2015, we conducted a case–control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups.
Results
After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types.
Conclusions
We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.
Genetic predisposition increases the risk of familial breast cancer. Recent studies indicate that genetic predisposition for familial breast cancer can be ethnic-specific. However, current knowledge ...of genetic predisposition for the disease is predominantly derived from Western populations. Using this existing information as the sole reference to judge the predisposition in non-Western populations is not adequate and can potentially lead to misdiagnosis. Efforts are required to collect genetic predisposition from non-Western populations. The Egyptian population has high genetic variations in reflecting its divergent ethnic origins, and incident rate of familial breast cancer in Egypt is also higher than the rate in many other populations. Using whole exome sequencing, we investigated genetic predisposition in five Egyptian familial breast cancer families. No pathogenic variants in BRCA1, BRCA2 and other classical breast cancer-predisposition genes were present in these five families. Comparison of the genetic variants with those in Caucasian familial breast cancer showed that variants in the Egyptian families were more variable and heterogeneous than the variants in Caucasian families. Multiple damaging variants in genes of different functional categories were identified either in a single family or shared between families. Our study demonstrates that genetic predisposition in Egyptian breast cancer families may differ from those in other disease populations, and supports a comprehensive screening of local disease families to determine the genetic predisposition in Egyptian familial breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM：To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.METHODS：The Gharbiah cancer registry ...is the only population-based cancer registry in Egypt since 1998.We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007.All medical records of the 1364 patients diagnosed in Gharbiah during the study period were retrieved and the following information abstracted：age,residence,diagnosis date,grade,stage,topology,clinical characteristics,and histology variables.Egyptian census data for 1996 and 2006 were used to provide the general population＇s statistics on age,sex,residence and other related demographic factors.In addition to age-and sex-specific incidence rate analyses,we analyze the data to explore the incidence distribution by rural-urban differences among the 8 districts of the province.We also compared the incidence rates of Gharbiah to the rates of the Surveillance Epidemiology and End Results（SEER） data of the United States.RESULTS：Over the 9 year-period,1364 colorectal cancer cases were included.The disease incidence under age 40 years was relatively high（1.3/10 5） while the incidence in the age groups 40 and over was very low（12.0/10 5,19.4/10 5 and 21.2/10 5 in the age groups 40-59 years,60-69 years and 〉 70 years,respectively）.The vast majority of tumors（97.2%） had no polyps and 37.2% of the patients presented with primary lesions in the rectum.Colorectal cancer was more common in patients from urban（55%） than rural（45%） areas.Regional differences in colon and rectal cancer incidence in the 8 districts of the study province may reflect different etiologic patterns in this population.The registry data of Egypt shows a slightly higher incidence of colorectal cancer than the United States in subjects under age 40 years.The results also shows significantly lower incidence of colorectal cancer in subjects over age 40 years compared to the same age group in the United States SEER.CONCLUSION：Low rate of polyps,low incidence in older subjects,and high rate of rectal cancer in Egypt.Future studies should explore clinical and molecular disease patterns.
Background. Pancreatic cancer is one of the deadliest forms of cancer, with incidence rates rising in many countries around the world. Geographic variation in pancreatic cancer incidence has not been ...studied extensively, especially in low- and middle-income countries. The aim of this study was to characterize the distribution of pancreatic cancer incidence in the central Nile Delta region of Egypt and to examine differences by urban and rural patient residence using the nation’s only population-based cancer registry. Methods. Utilizing the Gharbiah province population-based cancer registry, data were abstracted for 1,089 pancreatic cancer cases diagnosed over twelve years from 1999 to 2010. Age- and sex-specific incidence rates were calculated and compared for urban and rural areas of the eight districts of Gharbiah. Results. Age-adjusted incidence of pancreatic cancer within Gharbiah varied considerably by urban/rural patient residence and by district. Incidence rates were 1.3 times higher in urban compared to rural areas (4.45 per 100,000 in urban areas and 3.43 per 100,000 in rural areas). The highest incidence rates were observed in urban centers of Kotour, El Santa, and Kafr El-Zayat districts (12.94, 8.32, and 7.89, respectively). Conclusion. Incidence rates varied greatly by urban and rural areas and by district of residence in the Nile Delta region of Egypt. Future studies should examine potential environmental risk factors that may contribute to the geographic distribution of pancreatic cancer in this region.
There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal ...studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends.
Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing.
CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change.
These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The ...objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt.
We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans.
Monoethyl phthalate (MEP), was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban). Concentrations of urinary metabolites of di-(2-ethylhexyl) phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP) concentrations when comparing covariate adjusted means.
Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer mortality globally. HCC incidence has doubled in Egypt in the past 10 years, which could be ...attributed to the high prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV), although HBV rates have declined after the introduction of the vaccine in 1992. Aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy is the current gold standard for methylation studies; however, imaging techniques often suffice for diagnosis making tissue samples increasingly scarce. The efficacy of conducting DNA methylation studies in molecular epidemiology using plasma DNA is still unclear. We compared tumor methylation profile for the tumor suppressor genes APC, FHIT, p15, p16, and E-cadherin in tumor tissues and plasma to test the concordance between the two types of specimen from the same HCC patients. Twenty-eight HCC patients with matching tissue and plasma DNA were recruited from a case—control study in Gharbiah, Egypt. Concordance between the tissue and plasma was statistically significant in all five genes as follows: APC (23/28, 82.1%,
p=0.001), FHIT (24/28, 85.7%,
p=.0001), p15 (25/28, 89.2%,
p=0.045), p16 (19/28, 67.9%,
p=0.037), and E-cadherin (22/28, 78.5%,
p=0.0008). The average specificity was 90%, 86%, 96%, 86%, and 100%, respectively. There was no significant association between methylation and hepatitis viral infection for any of the genes tested in this study. Plasma DNA can be reliable for testing methylation profile in liver cancer patients in this population. Future studies on a larger sample size should investigate methylation profile in populations with higher rates of HBV, HCV, and other risk factors.
Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the ...potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt.
We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure.
Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA.
Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim: Hepatocellular carcinoma (HCC) is increasing worldwide, and is frequently attributed to rising rates of hepatitis C virus infection and interactions between viral and environmental risk ...factors. Because of Egypt's unique risk factor profile, we analyzed data from the Gharbiah Population‐Based Cancer Registry for the period 1999–2003 to characterize demographic and geographic patterns of cases in this province.
Methods: We calculated age‐ and sex‐specific and age‐ and sex‐standardized HCC incidence rates for the eight districts in Gharbiah. We also compared rates from Gharbiah with the USA (US Surveillance Epidemiology and End Results SEER database).
Results: The analysis revealed a higher incidence in males than in females, significant geographic variations among districts, and a higher incidence in Gharbiah than that reported by SEER.
Conclusion: The findings of this study document the heterogeneous distribution of HCC at regional and international levels. This population‐based registry offers the opportunity for careful representative studies of various etiologies, particularly infectious and/or environmental factors that may contribute to risk.
Background
Adenosine signaling is now an accepted explanation for the therapeutic mechanism of Methotrexate (MTX) in rheumatoid arthritis (RA). Adenosine receptors categorized into four subclasses: ...adenosine A1 receptor (ADORA1), adenosine 2a receptor (ADORA2a), adenosine 2b receptor (ADORA2B), and adenosine 3 receptor (ADORA3). Our aim is to check the mRNA expression of two adenosine receptors; ADORA2a and ADORA3 in whole blood cell of RA patients and its relation in prediction of MTX clinical response in Egyptian patients.
Results
There was significant correlation between both ADORA2a and ADORA3 gene expression in RA patients as compared with healthy controls. The expression of ADORA2a and ADORA3 was increased in good and moderate response groups compared to no response group. There was significant correlation between both genes in mRNA expression before and after MTX treatment. Matrix metalloproteinase-3 (MMP3) concentration was significantly decreased after treatment in good and moderate response groups in comparison to non-responder group.
Conclusion
The inflammatory and clinical responses in RA patients which is demonstrated by DAS28 and suppression of MMP3 were regulated by ADORA2a and ADORA3. Their level of expression can predict MTX response and their agonists may offer a novel and effective therapeutic option for RA patients.
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