Familial vs sporadic multiple sclerosis in the Israeli population: Differences in ethnicity distribution and disease progression, with anticipation in successive generations.

BACKGROUND: Multiple Sclerosis (MS) may cluster in families, an entity known as familial MS (FMS), possibly due to aggregation of genetic and environmental factors. Though previous studies have characterized FMS in different populations, no study to the best of our knowledge has yet characterized FMS in the unique Israeli population, which is comprised of relatively endogamous ethnicities. Our goal in this study was to compare demographic and clinical characteristics between FMS and sporadic MS (SMS), and to search for intra-familial patterns. METHODS: In a retrospective study of 101 FMS patients and 508 SMS patients, ethnicity and sex distribution was assessed. Clinical aspects were compared between 172 paired FMS and SMS patients, matched for sex, age and ethnicity, and between generations of the FMS cohort. RESULTS: Females comprised 75.3 % of FMS and 67.5 % of SMS patients (p = 0.1). Ethnic distribution was significantly different between FMS and SMS (p = 0.014), with the former comprising a higher proportion of Christian-Arabs (15.4% vs. 5.1 %, p = 0.004) and lower proportion of Jews (60% vs. 74.2 %, p = 0.016). Age at disease onset or diagnosis, frequency of positive Oligoclonal bands and comorbidity of other autoimmune/inflammatory disease or chronic diseases was comparable between FMS and SMS, yet motor symptoms at onset were more prevalent in FMS (34% vs. 20 %, p = 0.02). Annualized relapse rates throughout 10 years from onset were comparable. Among FMS, mean Expanded-Disability-Status-Scale (EDSS) and slope of deterioration in EDSS over 20 years from diagnosis were higher (p = 0.0004 and p = 0.023, respectively), time to EDSS ≥ 3 was shorter (7.1 vs. 12.1 years, HR 1.6, p = 0.036) and MS-Severity-Score (MSSS) was higher (3.84 vs. 2.95, p = 0.04), compared to SMS. Following adjustment for smoking, which tended to be higher among FMS patients (P = 0.06), mean EDSS and slope of deterioration in EDSS over 20 years remained significantly higher (p = 0.0006 and p = 0.025, respectively) in FMS, time to EDSS ≥ 3 tended to be higher (HR 1.5, p = 0.06), while MSSS was comparable. An inter-generational analysis of the total FMS cohort, as well as an intra-familial analysis, both adjusted for year of diagnosis, revealed significantly earlier age of onset (p < 0.0001 and p < 0.0001) and diagnosis (p = 0.001 and p < 0.0001) in the younger compared to the older generations, respectively. CONCLUSION: In this Israeli cohort, the proportions of specific ethnicities differ between FMS and SMS, indicating that FMS has a population-specific prevalence pattern, and that further investigation for susceptibility genes is warranted. Disease progression is faster in FMS patients and anticipation is observed in families with multiple cases of MS. Closer surveillance and application of a pro-active induction or early highly-effective therapeutic strategy for FMS patients should be considered, to reduce high disease activity and fast disability progression.

Age at diagnosis of cancer in 185delAG BRCA1 mutation carriers of diverse ethnicities: tentative evidence for modifier factors.

Germline pathogenic sequence variants (PSVs) in BRCA1 substantially increase risk for developing breast (BC) and ovarian cancer (OvC). Yet, incomplete penetrance suggests that modifier factors affect phenotypic expression of mutant BRCA1 alleles. Analysis of identical BRCA1 PSV carriers of diverse ethnicities may provide further evidence for modifier factors. Female carriers of the 185delAG BRCA1 PSV identified through high-risk clinics in Israel, and Manchester England from 1998-2018 were eligible. Data were retrieved from patients records and confirmed (in Israel) by cross referencing with the Israeli National Cancer Registry. Overall, 2503 female carriers were included: 1715 (71.4%) Ashkenazi Jews (AJ), 201 (8.3%) Iraqi Jews and 383 (15.9%) of mixed ethnicity. In 102 (4.2%) cases ethnicity could not be ascertained. Of Israeli AJ carriers 649 (37.8%), 256 (14.9%) and 62 (3.6%) were diagnosed with BC, OvC or both cancers, respectively. For the Iraqi Jews these frequencies were 76 (37.8%), 43 (21.4%), and 8 (3.98%), respectively. Age at diagnosis of BC in AJ and Iraqi Jews was 46.7 ± 12.3 years and 52.8 ± 12.2 years, respectively (p = 0.001). For OvC age at diagnosis for AJ was 53.5 ± 10.7 years and for Iraqi Jews 50.1 ± 8.8 years (p = 0.0027). No differences in these parameters were noted between English Jews (n = 110) and non-Jews (n = 32). Age at diagnosis of BC and OvC differs between AJ and Iraqi Jews who carry an identical BRCA1 PSV. This finding supports the existence of modifier factors that may be ethnic specific.

Age at Onset of Parkinson's Disease Among Ashkenazi Jewish Patients: Contribution of Environmental Factors, LRRK2 p.G2019S and GBA p.N370S Mutations.

BACKGROUND: Both genetic and environmental factors contribute to Parkinson's disease (PD) risk. OBJECTIVE: We investigated the potential association of several relevant variables with PD age at onset (AAO), focusing on LRRK2 p.G2019S and GBA p.N370S mutations. METHODS: Ashkenazi Jewish (AJ) PD patients, screened for LRRK2 and GBA mutations, underwent an interview regarding exposure to the following environmental and lifestyle factors: cigarette smoking, consumption of coffee, tea and alcohol, head injury and rural living. Multivariate linear regression (adjusted for sex) was used to examine the association with AAO, and models included LRRK2 p.G2019S and GBA p.N370S mutation status (carrier/non-carriers), single environmental variable and their interactions terms, as independent variables. RESULTS: 225 Israeli AJ PD patients were enrolled: 65 LRRK2 p.G2019S mutation carriers, 60 GBA p.N370S carriers and 100 non-carries of these mutations. In the dichotomized exposure/non-exposure analyses, positive LRRK2 p.G2019S status was associated with younger AAO in all models, at nominal or near significant levels (p = 0.033-0.082). Smoking was associated with older AAO (p = 0.032), and the interaction between GBA p.N370S and history of head injury was associated with younger AAO (p = 0.049), both at nominal significance. There was no indication of a consistent main effect for GBA p.N370S status or significant LRRK2 p.G2019S-environmental factor interaction. In the dose-dependent analyses, increased coffee and tea consumption levels were associated with older AAO (p = 0.001 and p = 0.002, respectively). CONCLUSIONS: Our results suggest that genetic and environmental factors may affect AAO in PD patients, but validation in additional samples is required.

Ethnic Disparities for Gynecologic Cancers in Israel.

BACKGROUND: Israel's unique population is comprised of two main ethnic groups-Jews (75%) and Arabs (21%), with differing socioeconomic, cultural, and genetic profiles. This study's objective was to evaluate disparities in the incidence, presentation, and outcomes of gynecologic cancers among Israeli women of Arab and Jewish ethnicity. METHODS: Data on the Israeli female population diagnosed with gynecologic cancers during the years 2000-2012 was obtained from the National Cancer Registry and the National Population Registry. Disease incidence rates by ethnic origin were calculated, and the "Segi World standard population" was used for age standardization. Data for Jewish and Arab patients was compared using chi-square test for categorical variables and T test for continuous variables. Survival outcomes were compared using the log-rank test and Cox proportional hazards modeling. RESULTS: Annual ASR (age-standardized rate) for ovarian, cervical, and uterine cancers, are all significantly higher among Israeli women of Jewish ethnicity. Israeli Arab women are diagnosed with cervical cancer at an older age (mean, 60.9 vs 55.9, p < 0.001). Stage distribution for uterine, ovarian, and cervical cancers is similar in both ethnic groups. The age-adjusted hazard ratio for mortality from uterine cancer is significantly lower among Jewish Israeli women compared to Arab Israeli women (HR = 0.67, 95% CI 0.57-0.78, p < 0.0001). During the study period, there was a significant decline in the ASR for ovarian cancer among Jewish Israeli women. The ASR for pre-invasive cervical disease increased significantly in both ethnic groups. CONCLUSIONS: Disparities in gynecological cancer rates, presentations, and outcomes are evident between two major ethnic groups in Israel. Lower cancer incidence rates among Israeli Arab women are likely multifactorial. Uterine cancer outcomes between the two ethnic groups need to be further assessed in order to identify opportunities for improved outcomes among Israeli Arab women.

Echoes from the past- changing associations between brain tumors and ethnicity.

BACKGROUND: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity. METHODS: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry. The first cohort included 376,336 participants born in 1948-1959 (when treatment with cranial X radiation was standard care for treating tinea capitis), and the second 474,923 participants born in 1960-1971. RESULTS: In the first cohort, ethnicity was strongly associated with the incidence of brain tumor (BT), with higher incidence observed among patients with origins in North Africa or the Middle East. This effect was ablated in the second cohort, and a significant decrease in the rate of meningiomas was noted. CONCLUSION: The association of brain tumor with ethnicity was present only during the period when treatment with cranial X radiation was the standard of care for TC in Israel, therefore it is most likely that radiation exposure was a confounding factor, and that ethnic susceptibility for brain cancer was not causative in these cohorts.

Ethnic differences of children with foreign body aspiration: a need for preventive education.

INTRODUCTION: Only in 2005 was a product labeling law passed in Israel that requires food companies to mark a choking hazard. We wished to investigate the influence of the hazard warning on the number of foreign body aspirations (FBA) in Israel, as well as the racial differences in the prevalence of and death rates from FBA. MATERIALS AND METHODS: All the medical records of patients under the age of 14 who arrived at our center's emergency department between the years 2007 and 2015 with suspected FBA were retrospectively reviewed. Population data was extracted from the Central Bureau of Statistics. RESULTS: Overall, 90 children arrived at the hospital with suspected FBA during 2007-2015. Forty-six (51%) of the patients were males, the mean age was 3.5 years. Seventy-one bronchoscopies were performed due to high suspicious presence of a foreign body. The most common objects aspirated were different types of nuts and seeds. In all cases, the patient's parents witnessed the aspiration of the foreign body. Most children (77, 86%) were of Arab ethnicity. The yearly prevalence of FBA in children 0-4 years of Arab ethnicity was 16.6:100,000 compared to 6.0:100,000 in the non-Arab population (p < 0.001). CONCLUSION: FBA is still a common injury in our region. Since most cases are preventable, efforts should be targeted among the population at higher risk, which are parents of children under the age of 4 and parents of Arab ethnicity. We believe that national effort and support for preventive education are needed.

The yield of full BRCA1/2 genotyping in Israeli Arab high-risk breast/ovarian cancer patients.

PURPOSE: While the spectrum of germline mutations in BRCA1/2 genes in the Israeli Jewish population has been extensively studied, there is a paucity of data pertaining to Israeli Arab high-risk cases. METHODS: Consecutive Israeli Arab breast and/or ovarian cancer patients were recruited using an ethically approved protocol from January 2012 to February 2019. All ovarian cancer cases were referred for BRCA genotyping. Breast cancer patients were offered BRCA sequencing and deletion/duplication analysis after genetic counseling, if the calculated risk for carrying a BRCA mutation by risk prediction algorithms was ≥10%. RESULTS: Overall, 188 patients participated; 150 breast cancer cases (median age at diagnosis: 40 years, range 22-67) and 38 had ovarian cancer (median age at diagnosis: 52.5 years, range 26-79). Of genotyped cases, 18 (10%) carried one of 12 pathogenic or likely-pathogenic variants, 12 in BRCA1, 6 in BRCA2. Only one was a rearrangement. Three variants recurred in more than one case; one was detected in five seemingly unrelated families. The detection rate for all breast cancer cases was 4%, 5% in bilateral breast cancer cases and 3% if breast cancer was diagnosed < 40 years. Of patients with ovarian cancer, 12/38 (32%) were carriers; the detection rate reached 75% (3/4) among patients diagnosed with both breast and ovarian cancer. CONCLUSIONS: The overall yield of comprehensive BRCA1/2 testing in high-risk Israeli Arab individuals is low in breast cancer patients, and much higher in ovarian cancer patients. These results may guide optimal cancer susceptibility testing strategy in the Arab-Israeli population.

Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A.

OBJECTIVES: Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited. METHODS: We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of BMPR1A. We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis. RESULTS: Patients with JPS from 7 families of Bukharin Jewish ancestry carried a deletion of 429 kb, encompassing the BMPR1A coding sequence and 8 downstream genes. Haplotype analysis and testing controls identified this as a common founder mutation occurring in 1/124 individuals of Bukharin origin. Tumor testing did not demonstrate loss of heterozygosity. Among carriers, JPS was almost fully penetrant, but clinical features varied widely, ranging from mild to very severe, including pan-enteric polyps, gastritis, and colorectal, esophageal, and testicular cancer, and carriers with phenotypes, which would not have raised suspicion of JPS. DISCUSSION: The phenotype in this large cohort was extremely variable, although all carriers shared the same variant and the same genetic background. New observations include a preponderance of adenomatous rather than juvenile polyps, possible association with testicular cancer, and unexpected upper gastrointestinal involvement.

Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel.

OBJECTIVES: HIV elite controllers (ECs) are a unique subgroup of HIV-positive patients who are long-term virologically suppressed in the absence of antiretroviral treatment (ART). The prevalence of this subgroup is estimated to be < 1%. Various cohorts of ECs have been described in developed countries, most of which have been demographically heterogeneous. The aim of this study was to identify ECs in two large African cohorts and to estimate their prevalence in a relatively genetically homogenous population. METHODS: We screened two cohorts of HIV-positive Ethiopian patients. The first cohort resided in Mekelle, Ethiopia. The second was comprised of HIV-positive Ethiopian immigrants in Israel. In the Mekelle cohort, ART-naïve subjects with stable CD4 counts were prospectively screened using two measurements of viral load 6 months apart. Subjects were defined as ECs when both measurements were undetectable. In the Israeli cohort, subjects with consistently undetectable viral loads (mean of 17 viral load measurements/patient) and stable CD4 count > 500 cells/µL were defined as ECs. RESULTS: In the Mekelle cohort, 16 of 9515 patients (0.16%) fitted the definition of EC, whereas seven of 1160 (0.6%) in the Israeli cohort were identified as ECs (P = 0.011). CONCLUSIONS: This is the first large-scale screening for HIV-positive ECs to be performed in entirely African cohorts. The overall prevalence of ECs is within the range of that previously described in developing countries. The significant difference in prevalence between the two cohorts of similar genetic background is probably a consequence of selection bias but warrants further investigation into possible environmental factors which may underlie the EC state.

Fear of catastrophic health expenditures and unrealistic expectations from supplementary health insurance: ethnic differences.

BACKGROUND: In Israel, the whole population is covered by comprehensive universal health insurance. Despite that, most of the population purchases supplementary health insurance (SHI). It has been shown that individuals purchase more health insurance and preventive medicine when they are uncertain of their state of health, while a majority may not fully understand basic concepts in their health insurance coverage. The purpose of this study was to examine the role of fear of catastrophic health expenditures and unrealistic expectations in purchasing SHI, which does not cover expenses for life-threatening illnesses. METHODS: A cross-sectional survey was conducted among random samples of 814 Jews and 800 Arabs in Israel. A structured questionnaire was administered by telephone using random digit dialling. Log-linear regression was used to identify factors associated with reasons for purchasing SHI and expectations from SHI. RESULTS: The most common reason for purchasing SHI was fear of catastrophic health-related expenditures (41%). The most important service expected from SHI was 'cancer medications' (mean 4.68 [standard deviation 0.87]). Differences in the reasons for purchasing SHI and in expectations from SHI were found according to population group, age, gender and education. CONCLUSIONS: Consumers' misconceptions and fear of catastrophic health expenditures are major factors leading to the purchase of SHI, despite universal health coverage. Improved and accessible information should help consumers make informed decisions as to whether or not to purchase SHI.

Hairy Cell Leukemia: Retrospective Analysis of Demographic Data and Outcome of 203 Patients from 12 Medical Centers in Israel.

BACKGROUND/AIM: In this retrospective study, we summarized the national Israeli experience with hairy cell leukemia (HCL) in a large cohort of patients with a long follow-up. PATIENTS AND METHODS: Demographic data, and relevant laboratory and clinical parameters were analyzed, emphasizing the outcome after first-line treatment with cladribine. RESULTS: Data on 203 patients was collected from 12 medical centers during 1985-2015. Mean and median follow-up were 7.5 years and 5.18 years (interquartile range=0.1-40 years), and 5- and 10-year survival were 96% and 90.62%, respectively. The median age of diagnosis was 55.5 years for Jews and 49 years for Arabs (p=0.021), and most patients were males (81.77%); 52.2% were Ashkenazi Jews, 36.1% Sephardic Jews and 11.7% were Arab, Druze or other ethnicity. Cladribine was given to 159 patients (80.7%%) and most (62%) received intravenous (i.v.) and 38% received subcutaneous (s.c.) therapy. Overall survival and time to next treatment were not significantly different between the two schedules (i.v., s.c.). In univariate analysis of a variety of factors, only age >65 years had a negative impact on outcome, with shorter overall survival. It is of interest that Arab patients with HCL were diagnosed at an earlier age, but had a similar clinical course and outcome to both Ashkenazi and Sephardic Jews.

Short and long-term prognosis following acute myocardial infarction according to the country of origin. Soroka acute myocardial infarction II (SAMI II) project.

BACKGROUND: Reports from many countries have shown birthplace-associated disparities in the incidence and mortality following acute myocardial infarction (AMI). The aims of the study were to identify and compare short- and long-term post-AMI mortality according to birthplace. METHODS: A retrospective analysis of Israeli AMI patients from a tertiary medical center in Southern Israel throughout 2002-2012. DATA SOURCE: the hospital's computerized systems. Patients were classified according to the country of birth (Israel, Southern Europe/Balkans, Northern Africa, Eastern/Central Europe, India/Pakistan, Middle-East, Yemen, and Ethiopia). STUDY OUTCOMES: in-hospital and up to 10-years post-discharge all-cause mortality. RESULTS: The study included 11,143 patients, age 67.4 ±â€¯13.9 and 67.5% men. Israeli-born patients were significantly younger, with lower rate of diabetes mellitus and hypertension but significantly higher rate of obesity, smoking, history of coronary artery disease and male sex compared with immigrants. The rate of STEMI and administration of percutaneous coronary revascularization was higher, yet extent of coronary findings and severe left ventricular dysfunction was lower in Israeli-born patients. In-hospital as well as post-discharge 1-and 10-year mortality rates were approximately 65% lower in Israeli-born patients compared with immigrants. Following adjustment for potential confounders the inequalities in post-discharge mortality attenuated (Yemen OR = 2.3 [95%CI: 1.4-3.6], Southern Europe/Balkans 1.75 [1.2-2.5], Northern Africa 1.5 [1.3-1.8], Eastern/Central Europe 1.4 [1.2-1.7] and India/Pakistan 1.4 [1.1-1.9], for 10-years mortality, p < 0.05 for each) and those for in-hospital mortality disappeared. CONCLUSIONS: Immigrants are at increased risk for post-discharge, yet not in-hospital mortality following AMI. Appropriate targeted preventive programs are required for these groups of patients.

Prevalence, Correlates, and Time Trends of Multiple Chronic Conditions Among Israeli Adults: Estimates From the Israeli National Health Interview Survey, 2014-2015.

INTRODUCTION: Chronic diseases constitute a major public health challenge. The prevalence of multiple chronic conditions (MCC) has increased. The objective of our study was to describe the prevalence, correlates, and time trends of MCC in the Israeli population and among the nation's 2 main population groups (Jewish and Arab). METHODS: To describe the prevalence of correlates of MCC, we used data from the 2014-2015 Israeli National Health Interview Survey-III (INHIS-III). MCC was defined as having 2 or more of the following 10 self-reported physician-diagnosed chronic conditions: asthma, arthritis, cancer, diabetes, dyslipidemia, heart attack, hypertension, migraine, osteoporosis, or thyroid disease. For trend analysis, we used data from INHIS-I (2003-2004) and INHIS-II (2007-2010). Logistic regression was used for multivariate analysis. Estimates were weighted to the 2014 Israeli population. P for trend was calculated by using the Cochran-Armitage test for proportions. RESULTS: In 2014-2015, the prevalence of MCC was 27.3% (95% confidence interval, 25.7%-28.8%). In multivariate analysis, MCC was associated with older age, female sex, a monthly household income of USD$3,000 or less, current and past smoking, and overweight or obesity. After adjusting for age, sex, income, smoking status, and body mass index, differences in MCC between Jewish and Arab populations disappeared. Dyslipidemia and hypertension were the most prevalent dyad among both men and women. Dyslipidemia, hypertension, and diabetes were the most prevalent triad among both men and women. The age-adjusted prevalence of MCC increased by 6.7% between 2003-2004 and 2014-2015. CONCLUSION: With the increase in the prevalence of MCC, a comprehensive approach is needed to reduce the burden of chronic conditions. Of special concern are the groups most prone to MCC.

Effect of ethnic origin and gender on the clinical manifestations of myasthenia gravis among the Jewish population in Israel.

Reports on patients with myasthenia gravis (MG) of different ethnic origins demonstrated differences in weakness distribution and serological results. We studied MG characteristics in a cohort of Ashkenazi (ASH) and non-Ashkenazi (NASH) Jewish origin according to their ethnic origins and gender. The frequency of age of MG onset was distributed in a bi-modal fashion in the female patients and increased gradually over time, with a peak around 70years of age in the male patients. Ocular MG was more frequent in males and ASH patients. Unlike previous reports, our male patients had a higher proportion of positive serum anti-acetyl choline receptor (AChR) than female patients, with no ethnic-based differences in the rates of anti-AChR or anti-muscle specific kinase. Comorbidity with another autoimmune disease was more frequent among female patients with late-onset MG and NASH patients (mainly Israel-born). Male MG patients tended to have more malignant comorbidities than female MG patients. These results demonstrate the effect of ethnicity on clinical aspects of MG within the Jewish population in Israel, and reveal novel effects of gender-associated comorbidities in patients with MG.

Familial chronic lymphocytic leukemia in Israel: A disproportionate distribution among Ashkenazi Jews.

BACKGROUND: Relatives of patients with chronic lymphocytic leukemia (CLL) are at increased risk of developing CLL. Familial CLL is defined as more than one case of CLL among blood relatives, a phenomenon reported in approximately 5%-10% of all CLL patients. OBJECTIVE: Given the known predisposition of CLL among Ashkenazi Jews, we studied the features of familial CLL in an Israeli population. METHODS: This is a retrospective study, in which we reviewed the demographics, clinical characteristics, and outcomes of a total of 332 patients with CLL/small lymphocytic lymphoma. RESULTS: Familial CLL was recorded in 41 cases (12.3%) of the patients. The age at diagnosis was younger in patients with familial CLL (by almost 3.5 years). Familial CLL was strongly associated with Ashkenazi Jewish origin. Patients with familial CLL more commonly presented with higher hemoglobin and lower serum ß-2-microglobulin levels. No significant differences were detected between sporadic and familial CLL in disease stage, time to treatment, second cancers, or overall survival. CONCLUSION: Familial cases of CLL in an Israeli population show a disproportionate ethnic distribution toward Jews of Ashkenazi origin. The clinical characteristics and the overall outcome are not substantially different from sporadic cases.

Incidence and epidemiology of non-Hodgkin lymphoma and risk of second malignancy among 22 466 survivors in Israel with 30 years of follow-up.

Previous studies have shown an increase risk of second malignancies after non-Hodgkin's lymphoma (NHL), which is probably related to a combination of factors including genetic predisposition, molecular background, host immunological status and therapy administered. Here, we determined the incidence of NHL and risk of second solid tumours and haematological malignancies among survivors of NHL diagnosed in Israel during 1980-2011. Data were collected from the records of the Israeli National Cancer Registry. The total cohort of 24 666 NHL-patients included 22 601 Jews and 2065 Arabs. Median age of diagnosis for Jews was 61.3 years and 48.2 for Arab patients. Of the Jews with NHL, 11 265 (50%) were of European-American origin, 5005 (22%) Asian or African and 6114 (27%) were born in Israel. Second cancers were recorded in 2010 NHL survivors, 1918 Jews and 92 Arabs, representing a rate of 8.5%, and 4.5% o, respectively. Second malignancies in all recorded sites were more frequent than in the general population, with a standardized incidence ratio (SIR) of 1.28 for Jewish men, 1.25 for Jewish women, 1.73 for Arab men and 1.98 for Arab women. This higher risk was even more pronounced for the 309 cases with secondary haematological malignancies (secondary haematological malignancies of 1.97, 1.81, 4.48 and 4.15, respectively). Our findings show that there is an increased risk of second malignancies occurring after diagnosis of NHL in Israel, particularly for haematological malignancies such as leukaemia and NHL. The differences we report in the incidence of NHL and the types of second malignancies occurring among Jews and Arabs suggest that ethnicity and genetic susceptibility may be important relevant risk factors. Copyright © 2016 John Wiley & Sons, Ltd.

Spousal concordance in the use of alternative tobacco products: A multi-country investigation.

BACKGROUND: Married couples often share similar health-related characteristics and behaviors, including cigarette smoking status. Despite their rising popularity in the U.S., little research has examined the patterns of spousal concordance (SC) for alternative tobacco products (ATPs), such as e-cigarettes, cigars, and hookah. METHODS: The purpose of this project was to examine the roles of age, gender, and culture in the strength of SC for these ATPs. Analyses focused on a diverse community sample of married individuals in Ohio, U.S. (N=278), but also examined patterns in Austria, Greece, Israel, the Netherlands, and Slovakia. All participants completed a survey in which they indicated both their own, and their spouse's ever-use of various tobacco products. RESULTS: For the U.S. sample, SC was highest for e-cigarettes, flavored e-cigarettes, flavored cigarettes, and hookah (ϕs=0.48- 0.61); SC appeared to be stronger among younger couples, and when there was only a small female vs. male differences in use. Similar patterns were found in the other countries, with a few key exceptions. In particular, there was low SC for e-cigarettes and flavored e-cigarettes in the other countries, where e-cigarettes had been federally regulated by the time of data collection. CONCLUSION: Overall, these findings have implications for the continued spreading popularity of these tobacco use behaviors.

Measured adolescent body mass index and adult breast cancer in a cohort of 951,480 women.

Body mass index (BMI) in adolescence, studied predominantly as a self-reported risk factor for breast cancer (BC), may have been subjected to recall bias. We examined the association between measured BMI in adolescence and the incidence of BC by menopausal status. 951,480 Jewish Israeli females aged 16-19 who underwent anthropometric measurements in 1967-2011 were followed up to 31.12.2012 for BC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as age-specific CDC percentiles) and time to BC diagnosis, adjusting for sociodemographic covariates. The analysis was also subdivided by age at diagnosis. 9619 BC cases diagnosed during 18,078,941 person-years of follow-up were included in multivariable analyses: 4901 premenopausal, 3809 perimenopausal, and 909 postmenopausal. Compared with 'healthy' BMI (5th-<85th percentiles) and adjusted for country of origin, education, and height, adolescent BMI was largely negatively associated with BC: hazard ratio (HR) = 1.057 (95 % confidence interval (CI) 0.955-1.169, p = 0.286) in underweight (<5th percentile); HR = 0.918 (95 % CI 0.849-0.993, p = 0.032) in overweight (85th-<95th percentiles); and HR = 0.682 (95 % CI 0.552-0.843, p = 0.00004) in obese (≥95th percentile) women. In premenopausal, but not peri- and postmenopausal BC, associations were statistically significant; underweight was associated with increased risk of premenopausal BC (HR = 1.15, 95 % CI 1.01-1.31, p = 0.037), and overweight and obesity with significantly lower risk. Adolescent thinness was associated with increased risk for early BC. Overweight and obesity were protectively associated with premenopausal but not postmenopausal BC. The lack of an association of adolescent overweight/obesity with increased peri- and postmenopausal BC suggests a causal role for adult weight gain.