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1.  A retrospective analysis of survival and prognostic factors of male breast cancer from a single center 
BMC Cancer  2014;14:227.
Background
Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients.
Methods
We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients’ OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis.
Results
In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS.
Conclusions
Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease.
doi:10.1186/1471-2407-14-227
PMCID: PMC3987167  PMID: 24673740
Male breast cancer; Overall survival; Prognostic factors; Hormone receptor status
2.  Risk Factors for Chronic Mastitis in Morocco and Egypt 
Chronic mastitis is a prolonged inflammatory breast disease, and little is known about its etiology. We identified 85 cases and 112 controls from 5 hospitals in Morocco and Egypt. Cases were women with chronic mastitis (including periductal, lobular, granulomatous, lymphocytic, and duct ectasia with mastitis). Controls had benign breast disease, including fibroadenoma, benign phyllodes, and adenosis. Both groups were identified from histopathologically diagnosed patients from 2008 to 2011, frequency-matched on age. Patient interviews elicited demographic, reproductive, breastfeeding, and clinical histories. Cases had higher parity than controls (OR = 1.75, 1.62–1.90) and more reported history of contraception use (OR = 2.73, 2.07–3.61). Cases were less likely to report wearing a bra (OR = 0.56, 0.47–0.67) and less often used both breasts for breastfeeding (OR = 4.40, 3.39–5.72). Chronic mastitis cases were significantly less likely to be employed outside home (OR = 0.71, 0.60–0.84) and more likely to report mice in their households (OR = 1.63, 1.36–1.97). This is the largest case-control study reported to date on risk factors for chronic mastitis. Our study highlights distinct reproductive risk factors for the disease. Future studies should further explore these factors and the possible immunological and susceptibility predisposing conditions.
doi:10.1155/2013/184921
PMCID: PMC3847959  PMID: 24327928
3.  Trends in Breast Cancer Incidence Rates by Age and Stage at Diagnosis in Gharbiah, Egypt, over 10 Years (1999–2008) 
Journal of Cancer Epidemiology  2013;2013:916394.
Background. This study was undertaken to evaluate trends in breast cancer incidence in Egypt from 1999 to 2008 and to make projections for breast cancer occurrence for the years 2009–2015. Patients and Methods. We utilized joinpoint regression and average annual percent change (AAPC) measures with 95% confidence intervals (CI) to describe the trends in breast cancer incidence rates from the Gharbiah Cancer Registry by age and stage at diagnosis and to estimate expected breast cancer caseloads for 2009–2015. Results. From 1999 to 2008, the AAPC in breast cancer incidence rates in Gharbiah significantly increased among women 50 years and older and among localized tumors (AAPC %, 95% CI, 3.1% to 8.0%). Our results predict a significant increase in breast cancer caseloads from 2009 to 2015 among women aged 30–39 (AAPC %, 95% CI, 0.9% to 1.1%) and among women aged 40–49 years (AAPC %, 95% CI, 1.0% to 2.6%). Conclusion. These results have important implications for allocating limited resources, managing treatment needs, and exploring the consequences of prior interventions and/or changing risk factors in Egypt and other developing countries at the same stages of demographic and health transitions.
doi:10.1155/2013/916394
PMCID: PMC3824336  PMID: 24282410
4.  Adherence to screening mammography among American Indian women of the northern plains 
Breast cancer is a burden for American Indian (AI) women who have younger age at diagnosis and higher stage of disease. Rural areas also have had less access to screening mammography. An Indian Health Service Mobile Women’s Health Unit (MWHU) was implemented to improve mammogram screening of AI women in the Northern Plains. Our purpose was to determine the past adherence to screening mammography at a woman’s first presentation to the MWHU for mammogram screening. Date of the most recent prior non-MWHU mammogram was obtained from mammography records. Adherence to screening guidelines was defined as the prior mammogram occurring 1–2 years before the first MWHU visit among women ≥41 years, and was the main outcome, whereas, age and clinic site were predictors. Adherence was compared with national data of the Breast Cancer Surveillance Consortium (BCSC). Among 1,771 women ≥41 years, adherence to screening mammography guidelines was 48.01 % among ≥65 years, 42.05 % among 50–64 years, 33.43 % among 41–49 years, and varied with clinic site (25.23–65.93 %). Age (p <0.0001) and clinic site (p <0.0001) were associated with adherence. Overall, adherence to screening mammography guidelines was found in 39.86 % (706/1771) of MWHU women versus 74.34 % (747,095/1,004,943) of BCSC women. The majority (60.14 %) of women at first presentation to the MWHU had not had mammograms in the previous 2 years, lower screening adherence than nationally (25.66 %). Adherence was lowest among women ages 41–49, and varied with clinic site. Findings suggest disparities in mammography screening among these women.
doi:10.1007/s10549-013-2580-4
PMCID: PMC3760373  PMID: 23749344
Screening mammography; Health mobile; American Indians; Mammography adherence; Health disparities
5.  Variation of cervical cancer incidence in Latin America and the Caribbean 
Objective
To provide a comprehensive analysis of the descriptive epidemiology of invasive cervical cancer in Latin America and the Caribbean by analyzing quality data from the area’s cancer registries, including data that were excluded from the International Agency for Research on Cancer (IARC) publication, Cancer Incidence in Five Continents, Vol. IX (CI5-IX).
Methods
This was a descriptive epidemiologic study that involved 20 cancer registries, 9 of which were included by IARC in CI5-IX, and 11 of which were not. Data on invasive cervical cancers diagnosed from 1998–2002 were obtained from IARC. A cervical cancer-specific quality assessment was performed on all registries whether or not they were included in CI5-IX. Data from 14 registries met quality criteria and were analyzed. Incidence rates were calculated and compared across registries.
Results
A substantial variation in incidence rates existed among the registries; age-standardized rates ranged from 14.6–44.0 per 100 000 women per year. Mean cervical cancer incidence rates were 10.4% higher for registries included in CI5-IX than for those excluded; however, this difference was not significant (P = 0.541).
Conclusions
This study compared cervical cancer rates from a more diverse group of Latin American and Caribbean countries than that of the CI5-IX. The heterogeneity found among registries highlights the importance of examining data from as many registries as possible when characterizing risk across a geographic area. Data from developing countries can be used to better understand cancer distribution and enable Region-specific recommendations on cancer control and prevention once data quality has been established.
PMCID: PMC3629916  PMID: 22858816
Uterine cervical neoplasms; incidence rate; Latin America; Caribbean region
6.  The age-specific prevalence of human papillomavirus and risk of cytologic abnormalities in rural Nigeria: Implications for screen-and-treat strategies 
Cervical screening for carcinogenic human papillomavirus (HPV) infection is being considered for low income countries. Effectiveness requires targeted screening in older women in whom prevalent infections are more likely to be persistent and predictive of precancer. Some studies in West Africa have found unusually high HPV prevalences across all adult ages, that may reduce the positive predictive value (PPV) of HPV-based screening, if positivity in older women does not sufficiently predict elevated risk. We conducted a population-based study in rural Nigeria to identify HPV prevalence and associated cervical abnormalities. Using stratified random sampling, we enrolled women age 15+. Non-virgins had a cervical exam including liquid-based cytology and PCR HPV DNA testing from residual cytology specimens. Two-thirds of invited women participated, and 14.7% had detectable carcinogenic HPV, a proportion that did not decline with age (p-trend=.36) and showed slight peaks in the 15–29 and 60–69 age groups. Among women of the age typically considered for screen-and-treat programs (30–49 years), 12.8% were HPV-positive and the PPV for high-grade or worse cytology was 16.4%. Comparatively, women age <30, were more likely to be HPV-positive (18.9%, p=.03) with a lower PPV (4.2% p=.05). Among women age 50+ (typically excluded from screening in resource-poor settings because inexpensive treatment is not available), HPV positivity was 14.2% with a PPV of 13.9%. In Irun and similar settings where HPV does not decline with age, HPV-based screen-and-treat programs might be feasible for mid-adult women, since prevalence is sufficiently low, positivity predicts elevated risk of more easily treated precancer.
doi:10.1002/ijc.26211
PMCID: PMC3227742  PMID: 21630264
HPV prevalence; age; screening
7.  Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt 
Environmental Health  2013;12:33.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1476-069X-12-33
PMCID: PMC3655072  PMID: 23590724
Bead array; Bisphenol A; Egypt; Epigenetics; DNA methylation
8.  Individual and Neighborhood Socioeconomic Status and Healthcare Resources in Relation to Black-White Breast Cancer Survival Disparities 
Journal of Cancer Epidemiology  2013;2013:490472.
Background. Breast cancer survival has improved significantly in the US in the past 10–15 years. However, disparities exist in breast cancer survival between black and white women. Purpose. To investigate the effect of county healthcare resources and SES as well as individual SES status on breast cancer survival disparities between black and white women. Methods. Data from 1,796 breast cancer cases were obtained from the Surveillance Epidemiology and End Results and the National Longitudinal Mortality Study dataset. Cox Proportional Hazards models were constructed accounting for clustering within counties. Three sequential Cox models were fit for each outcome including demographic variables; demographic and clinical variables; and finally demographic, clinical, and county-level variables. Results. In unadjusted analysis, black women had a 53% higher likelihood of dying of breast cancer and 32% higher likelihood of dying of any cause (P < 0.05) compared with white women. Adjusting for demographic variables explained away the effect of race on breast cancer survival (HR, 1.40; 95% CI, 0.99–1.97), but not on all-cause mortality. The racial difference in all-cause survival disappeared only after adjusting for county-level variables (HR, 1.27; CI, 0.95–1.71). Conclusions. Improving equitable access to healthcare for all women in the US may help eliminate survival disparities between racial and socioeconomic groups.
doi:10.1155/2013/490472
PMCID: PMC3590635  PMID: 23509460
9.  Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988–2008) 
SpringerPlus  2013;2:3.
Introduction
Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, little is known about disease patterns among Arab Americans because a racial category is rarely considered for this group. The aim of this study was to advance our understanding of the burden of IBC in Arab ethnic populations by describing the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology and End Results (SEER) registries.
Methods
We utilized a validated Arab surname algorithm to identify women of Arab descent from the SEER registries. Differences in the proportion of IBC out of all breast cancer and IBC characteristics by race and menopausal status were evaluated using chi-square tests for categorical variables, t-tests and ANOVA tests for continuous variables, and log-rank tests for survival data. We modeled the association between race and IBC among all women with breast cancer using hierarchical logistic regression models, adjusting for individual and census tract-level variables.
Results
Statistically significant differences in the proportion of IBC out of all breast cancers by race were evident. In a hierarchical model, adjusting for age, estrogen and progesterone receptor, human epidermal growth receptor 2, registry and census-tract level education, Arab-Americans (OR=1.5, 95% CI=1.2,1.9), Hispanics (OR=1.2, 95% CI=1.1,1.3), Non-Hispanic Blacks (OR=1.3, 95% CI=1.2, 1.4), and American Indians/Alaskans (OR=1.9, 95% CI=1.1, 3.4) had increased odds of IBC, while Asians (OR=0.6, 95% CI=0.6, 0.7) had decreased odds of IBC as compared to Non-Hispanic Whites.
Conclusions
IBC may be more common among certain minority groups, including Arab American women. Understanding the descriptive epidemiology of IBC by race may generate hypotheses about risk factors for this aggressive disease. Future research should focus on etiologic factors that may explain these differences.
doi:10.1186/2193-1801-2-3
PMCID: PMC3568481  PMID: 23420611
Inflammatory breast cancer; Arab; Race; Hierarchical logistic regression
10.  Association of Inflammatory and Non-Inflammatory Breast Cancer with Socioeconomic Characteristics in the Surveillance, Epidemiology, and End Results Database, 2000–2007 
Background
Inflammatory breast cancer (IBC) is a rare and highly aggressive form of primary breast cancer. Little is known regarding risk factors for IBC, specifically the association with socioeconomic position (SEP).
Methods
The association between breast cancer type (IBC vs. non-IBC) with county-level SEP in the Surveillance, Epidemiology, and End Results database for cases diagnosed from 2000–2007 was examined. County-level SEP characteristics included metropolitan vs. non- metropolitan residence, percent below the poverty level, percent less than high school graduate,and an index combining the poverty and high school variables. IBC and non-IBC age-adjusted incidence rates (IRs) were calculated, stratified on SEP and race/ethnicity. The odds of IBC vs. non-IBC given a particular SEP characteristic, adjusting for age and race/ethnicity, was examined through fitting of hierarchical logistic regression models (HLMs).
Results
IRs for IBC generally increased as SEP decreased, while the opposite was found for non-IBC. HLM results showed low SEP is associated with higher odds of IBC: Highest (≥ 20%) vs. lowest (<10%) persons below the poverty level Odds Ratio (95% Confidence Interval) = 1.25 (1.09–1.43); Highest (>28.76%) vs. lowest (≤15.99%) persons less than high school graduate = 1.25 (1.10–1.42); Low SEP as measured by poverty-high school index vs. high SEP = 1.26 (1.11–1.44).
Conclusion
Overall breast cancer has been found to be positively associated with SEP, whereas in this analysis IBC was associated with decreasing SEP.
Impact
Studies focused on understanding the disparity in IBC incidence, as well as interventions to eliminate these differences are needed.
doi:10.1158/1055-9965.EPI-11-0833
PMCID: PMC3254254  PMID: 22028401
Inflammatory Breast Cancer; Socioeconomic Position; Epidemiology; Incidence Rates; Hierarchical Logistic Regression
11.  Considerations in setting up and conducting epidemiologic studies of cancer in middle- and low-income countries: the experience of a case–control study of inflammatory breast cancer in North Africa in the past 10 years 
Cancer Medicine  2012;1(3):338-349.
This article illustrates some issues we faced during our experience in conducting an epidemiologic case–control study of inflammatory breast cancer in North Africa. We expect that some of the questions we had to ask in order to address these issues might be helpful to others in setting up epidemiologic studies in developing regions. We describe our experience from different angles including the use of multiple sites to achieve adequate sample size, standardizing diagnosis of disease, identifying cancer cases at the time of diagnosis, control selection procedures, logistics of study implementation, questionnaire development and interviewing, biologic specimens, and procedures for protection of human subjects. We have developed a brief checklist to summarize important issues for conducting future epidemiologic studies in these or similar low- or middle-income countries.
doi:10.1002/cam4.36
PMCID: PMC3544462  PMID: 23342283
Breast cancer; Egypt; epidemiology; field methods; Morocco; North Africa; Tunisia
12.  Age distribution, polyps and rectal cancer in the Egyptian population-based cancer registry 
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 (1.3/105) while the incidence in the age groups 40 and over was very low (12.0/105, 19.4/105 and 21.2/105 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.
doi:10.3748/wjg.v18.i30.3997
PMCID: PMC3419996  PMID: 22912550
Colorectal cancer; Young-onset; Polyps; Developing countries; Egypt
13.  Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study 
Environmental Health  2012;11:20.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1476-069X-11-20
PMCID: PMC3361671  PMID: 22472083
Egypt; Urban; Rural; Bisphenol A
14.  Healthcare access and mammography screening in Michigan: a multilevel cross-sectional study 
Background
Breast cancer screening rates have increased over time in the United States. However actual screening rates appear to be lower among black women compared with white women.
Purpose
To assess determinants of breast cancer screening among women in Michigan USA, focusing on individual and neighborhood socio-economic status and healthcare access.
Methods
Data from 1163 women ages 50-74 years who participated in the 2008 Michigan Special Cancer Behavioral Risk Factor Survey were analyzed. County-level SES and healthcare access were obtained from the Area Resource File. Multilevel logistic regression models were fit using SAS Proc Glimmix to account for clustering of individual observations by county. Separate models were fit for each of the two outcomes of interest; mammography screening and clinical breast examination. For each outcome, two sequential models were fit; a model including individual level covariates and a model including county level covariates.
Results
After adjusting for misclassification bias, overall cancer screening rates were lower than reported by survey respondents; black women had lower mammography screening rates but higher clinical breast examination rates than white women. However, after adjusting for other individual level variables, race was not a significant predictor of screening. Having health insurance or a usual healthcare provider were the most important predictors of cancer screening.
Discussion
Access to healthcare is important to ensuring appropriate cancer screening among women in Michigan.
doi:10.1186/1475-9276-11-16
PMCID: PMC3414751  PMID: 22436125
Mammography screening; Access to healthcare, Neighborhood effects; Socio-economic status
15.  Urban-rural differences in breast cancer incidence in Egypt (1999–2006) 
Breast (Edinburgh, Scotland)  2010;19(5):417-423.
Objective
To describe urban-rural differences in breast cancer incidence in Gharbiah, Egypt and to investigate if these differences could be explained by known risk factors of breast cancer.
Methods
We used data from the population-based cancer registry of Gharbiah, Egypt to assess breast cancer incidence from 1999 through 2006. The Egyptian census provided data on district-specific population, age, and urban-rural classification. Incidence patterns of breast cancer by district and age-specific urban-rural differences were analyzed.
Results
Overall, incidence rate of breast cancer was three to four times higher in urban areas than in rural areas (60.9/105/year for urban areas versus 17.8/105/year for rural areas; IRR = 3.73, 95% CI = 3.30, 4.22). Urban areas had consistently higher incidence of breast cancer across all age-groups for all years. Higher incidence of breast cancer was also seen in the more developed districts of Tanta and El-Mehalla.
Conclusions
Higher incidence of breast cancer in urban and more developed populations might be related to higher xenoestrogens, as well as other endocrine disruptors and genotoxic substances.
doi:10.1016/j.breast.2010.04.005
PMCID: PMC3209663  PMID: 20452771
Breast cancer; incidence; urban-rural; xenoestrogens; Egypt
16.  Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 Molar Ratio and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 
Background
Experimental evidence suggests that an overexpression of insulin-like growth factor-I (IGF-I) is implicated in human pancreatic tumors. Increased IGF-II and decreased insulin-like growth factor binding protein-3 (IGFBP-3) serum concentrations have been linked to a number of other cancers.
Methods
We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55–74 years of age at baseline, to test whether pre-diagnostic circulating IGF-I, IGF-II, IGFBP-3, andIGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n=374), who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex and date of blood draw. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for smoking.
Results
IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with pancreatic cancer (highest compared with lowest quartile, OR=1.58, 95% CI 0.91–2.76, p-trend=0.25; OR=0.86, 95% CI 0.49–1.50, p-trend=0.31; and OR=0.88, 95% CI 0.51–1.51, p-trend=0.47, respectively). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels (highest compared with lowest quartile OR=1.54, 95% CI 0.89–2.66, p-trend=0.04).
Conclusion
A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which maybe a risk factor for pancreatic cancer.
Impact
Our results highlight the importance of this biomarker for further investigation in large prospective cohort studies and pooled analysis with other prospective cohorts.
doi:10.1158/1055-9965.EPI-10-0400
PMCID: PMC2936681  PMID: 20699371
IGF-I; IGF-II; IGFBP-3; IGF-I/IGFBP-3; Pancreatic
17.  Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study 
Environmental Health  2011;10:40.
Background
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.
Materials and methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1476-069X-10-40
PMCID: PMC3112381  PMID: 21575223
18.  Incidence analyses of bladder cancer in the Nile delta region of Egypt 
Cancer epidemiology  2009;33(3-4):176-181.
Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region.
doi:10.1016/j.canep.2009.08.008
PMCID: PMC2763030  PMID: 19762298
bladder carcinoma; environmental exposures; developing countries; pollution; schistosomiasis
19.  Epidemiologic risk factors of hepatocellular carcinoma in a rural region of Egypt 
Hepatology International  2010;4(4):681-690.
Background
Hepatocellular carcinoma (HCC) is a major health problem worldwide, including Egypt. In the recent past, HCC has become the second most prevalent cancer among men in Egypt. Since HCC has not been well studied in the rural population of Egypt, this case–control study was conducted to investigate the epidemiologic risk factors of HCC in the predominantly rural region of Gharbiah, Egypt.
Methods
A total of 150 cases and 150 controls matched to cases on age (±5 years) and sex were recruited from the Gharbiah Cancer Society and Tanta Cancer Center. Exposure data were collected by an interviewer-administered standardized questionnaire about epidemiologic, occupational, medical and family history of HCC. Conditional logistic regression was utilized to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI). The effect modification of HCC risk between viral infection and environmental risk factors was also assessed.
Results
Being an industrial worker was an independent risk for developing HCC (OR 3.54, 95% CI 1.18, 10.63) after adjusting for viral infection, schistosomiasis and tobacco smoking. High relative risk of HCC was observed among HCV-infected individuals who were farmers (OR 9.60, 95% CI 3.72, 24.76), industrial workers (OR 12.90, 95% CI 4.33, 38.43) or active smokers (OR 5.95, 95% CI 2.20, 16.08).
Conclusion
Occupational exposure may play an important role in the development of HCC. Farming, industrial exposures and cigarette smoking may increase the risk of HCC among HCV-seropositive individuals. Future research focusing on mechanisms of occupational exposures among HCV patients in this population is needed.
doi:10.1007/s12072-010-9187-1
PMCID: PMC2994623  PMID: 21286338
Hepatocellular carcinoma; Rural; Gharbiah; Egypt
20.  Analysis of RhoC expression and lymphovascular emboli in inflammatory vs non-inflammatory breast cancers in Egyptian patients 
SUMMARY
Understanding the molecular factors that distinguish inflammatory breast cancer (IBC) from non-IBC is important for IBC diagnosis. We reviewed the records of 48 IBC patients and 64 non-IBC patients from Egypt. We determined RhoC expression and tumor emboli and their relationship to demographic and reproductive characteristics. Compared with non-IBC patients, IBC patients had significantly lower parity (P = 0.018) and fewer palpable tumors (P < 0.0001). IBC tumors showed RhoC overexpression more frequently than non-IBC tumors (87% vs. 17%, respectively) (P < 0.0001). Tumor emboli were significantly more frequent in IBC tumors than non-IBC tumors (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.0001). This study illustrates that RhoC overexpression and tumor emboli are more frequent in tumors of IBC relative to non-IBC from Egypt. Future studies should focus on relating epidemiologic factors to molecular features of IBC in this population.
doi:10.1016/j.breast.2008.11.002
PMCID: PMC2818070  PMID: 19157876
Inflammatory breast cancer; Tumor emboli; RhoC; Egypt; Developing countries
21.  Urban-rural differences in breast cancer incidence by hormone receptor status across 6 years in Egypt 
Breast cancer incidence is higher in developed countries with higher rates of estrogen receptor positive (ER+) tumors. ER+ tumors are caused by estrogenic exposures although known exposures explain approximately 50% of breast cancer risk. Unknown risk factors causing high breast cancer incidence exist that are estrogenic and development-related. Xenoestrogens are such risk factors but are difficult to study since developed countries lack unexposed populations. Developing countries have urban-rural populations with differential exposure to xenoestrogens. This study assessed urban-rural breast cancer incidence classified by hormone receptor status using data from Gharbiah population-based cancer registry in Egypt from 2001 to 2006. Urban ER+ incidence rate (per 100,000 women) was 2-4 times (IRR = 3.36, 95% CI = 4.84, 2.34) higher than rural incidence rate. ER− incidence rate was 2-3 times (IRR = 1.86, 95% CI = 2.38, 1.45) higher in urban areas than in rural areas. Our findings indicate that urban women may probably have a higher exposure to xenoestrogens.
doi:10.1007/s10549-009-0427-9
PMCID: PMC2808467  PMID: 19548084
Breast cancer incidence; hormone receptor status; mammary stem cells; xenoestrogens; Egypt
22.  Breast cancer characteristics at diagnosis and survival among Arab-American women compared to European- and African-American women 
Background
Data from Arab world studies suggest that Arab women may experience a more aggressive breast cancer phenotype. To investigate this finding, we focused on one of the largest settlements of Arabs and Iraqi Christians (Chaldeans) in the US, metropolitan Detroit- a SEER reporting site since 1973.
Materials and Methods
We identified a cohort of primary breast cancer cases diagnosed 1973–2003. Using a validated name algorithm, women were identified as being of Arab/Chaldean descent if they had an Arab last or maiden name. We compared characteristics at diagnosis (age, grade, histology, SEER stage, and marker status) and overall survival between Arab-, European-, and African-Americans.
Results
The cohort included 1,652 (2%) women of Arab descent, 13,855 (18%) African-American women, and 63,615 (80%) European-American. There were statistically significant differences between the racial groups for all characteristics at diagnosis. Survival analyses overall and for each SEER stage showed that Arab-American women had the best survival, followed by European-American women. African-American women had the poorest overall survival and were 1.37 (95% confidence interval: 1.23–1.52) times more likely to be diagnosed with an aggressive tumor (adjusting for age, grade, marker status, and year of diagnosis).
Conclusion
Overall, Arab-American women have a distribution of breast cancer histology similar to European-American women. In contrast, the stage, age, and hormone receptor status at diagnosis among Arab-Americans was more similar to African-American women. However, Arab-American women have a better overall survival than even European-American women.
doi:10.1007/s10549-008-9999-z
PMCID: PMC2804102  PMID: 18415013
Arab; breast cancer; epidemiology; incidence; survival
23.  Serum Cadmium Levels in Pancreatic Cancer Patients from the East Nile Delta Region of Egypt 
Environmental Health Perspectives  2005;114(1):113-119.
The northeast Nile Delta region exhibits a high incidence of early-onset pancreatic cancer. It is well documented that this region has one of the highest levels of pollution in Egypt. Epidemiologic studies have suggested that cadmium, a prevalent pollutant in the northeast Nile Delta region, plays a role in the development of pancreatic cancer.
Objective: We aimed to assess serum cadmium levels as markers of exposure in pancreatic cancer patients and noncancer comparison subjects from the same region in Egypt.
Design and Participants: We assessed serum cadmium levels of 31 newly diagnosed pancreatic cancer patients and 52 hospital comparison subjects from Mansoura, Egypt.
Evaluation/Measurements: Serum cadmium levels were measured using a novel immunoassay procedure.
Results: We found a significant difference between the mean serum cadmium levels in patients versus comparison subjects (mean ± SD, 11.1 ± 7.7 ng/mL vs. 7.1 ± 5.0 ng/mL, respectively; p = 0.012) but not in age, sex, residence, occupation, or smoking status. The odds ratio (OR) for pancreatic cancer risk was significant for serum cadmium level [OR = 1.12; 95% confidence interval (CI), 1.04–1.23; p = 0.0089] and farming (OR = 3.25; 95% CI, 1.03–11.64; p = 0.0475) but not for age, sex, residence, or smoking status.
Conclusions: The results from this pilot study suggest that pancreatic cancer in the East Nile Delta region is significantly associated with high levels of serum cadmium and farming.
Relevance to Clinical Practice/Public Health: Future studies should further investigate the etiologic relationship between cadmium exposure and pancreatic carcinogenesis in cadmium-exposed populations.
doi:10.1289/ehp.8035
PMCID: PMC1332665  PMID: 16393667
cadmium; East Nile Delta region; environmental exposure; immunoassays; occupational exposure; pancreatic cancer; pollution

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