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Background: Thyroid hormones heavily impact energy expenditure, body mass, and body composition. Their role in the state of exogenous subclinical hyperthyroidism in differentiated thyroid carcinoma (DTC) patients, however, is less well defined. The first aim of this study was to assess changes in body weight, body composition, resting energy expenditure (REE), respiratory quotient (RQ), and metabolic parameters in female DTC patients, starting from the phase of a euthyroid state before total thyroidectomy through the subsequent year after thyrotropin (TSH) suppression. The second aim was to assess the relationship between these variables and thyroid function parameters. Methods: This observational case series analyzed changes in body composition, calorimetric, and metabolic parameters of 15 DTC female patients at 5 time points: (1) at initial DTC diagnosis (euthyroid state), (2) at 2–3 weeks after thyroidectomy (hypothyroid state), (3) at 2–3 months of levothyroxine (LT4) treatment (exogenous euthyroid state), (4) after 6–9 months, and (5) after 1 year of TSH suppressive LT4 therapy (exogenous subclinical hyperthyroid state). A generalized estimating equation (GEE) analysis was performed to estimate the longitudinal correlations of the total triiodothyronine (TT3)/free thyroxine (fT4) ratio (as an independent variable) with body composition, metabolic, and calorimetric parameter changes (as dependent variables). Results: REE, REE per kilogram of lean body mass (REE/LBM), pulse, and systolic and diastolic blood pressure were significantly higher after TSH suppressive LT4 therapy. The GEE analysis revealed longitudinal negative correlations between the TT3/fT4 ratio and systolic blood pressure, fasting blood glucose, body mass index, android (abdominal wall and visceral mesentery) fat distribution, trunk, and arm fat distribution, REE, and REE/LBM. There was a positive correlation with RQ. Conclusions: REE, REE/LBM, pulse, and systolic and diastolic blood pressure were significantly higher after thyroidectomy, radioiodine and TSH suppressive therapy in female DTC patients, while no changes were observed in body weight or body composition. A lower TT3/fT4 ratio longitudinally correlated with increases in REE, REE/LBM, abdominal fat distribution, systolic blood pressure, and fasting blood glucose, as well as with decreased RQ. These findings highlight the importance of judicial balancing of the benefits and detriments of TSH suppression with subsequent decreased TT3/fT4 ratios for female DTC patients.

Objective Thyroid cancer (TC) survivors may be at risk of subsequent cardiovascular and cerebrovascular (CaV&CeV) morbidity. The 2009 American Thyroid Association (ATA) guidelines recommended less aggressive treatment for low-risk TC patients. The aim of this study was to assess the atherosclerotic CaV&CeV outcome of Israeli TC survivors compared to individuals with no thyroid disease, and the atherosclerotic CaV&CeV outcome before (2000–2008) and after (2009–2011) implementation of the 2009 ATA guidelines. Methods All members of the largest Israeli healthcare organization who were diagnosed with TC from 1/2000 to 12/2014 (study group) and age- and sex-matched members with no thyroid disease (controls) were included. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models. Results The mean follow-up was 7.6 ± 4.2 and 7.8 ± 4.1 years for the study (n = 5,677, 79% women) and control (n = 23,962) groups, respectively. The former had an increased risk of new atherosclerotic CaV&CeV events (adjusted HR 1.26, 95% CI 1.15–1.39). The 5-year incidence of CaV&CeV was lower (adjusted HR 0.49, 95% CI 0.38–0.62) from 2009 to 2011 compared to 2000 to 2008, but remained higher in the study group than in the control group (adjusted HR 1.5, 95% CI 1.14–1.69). Conclusions This large Israeli population-based cohort study showed greater atherosclerotic CaV&CeV morbidity in TC survivors compared to individuals with no thyroid diseases. There was a trend toward a decreased 5-year incidence of atherosclerotic CaV&CeV events among TC survivors following the implementation of the 2009 ATA guidelines, but it remained higher compared to the general population.

Background The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. Methods Individuals diagnosed with TC during 2001–2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. Results During a 15-year follow-up (median 8 years), 577 TC survivors out of 5677 (10.2%) TC patients and 1235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR = 1.89, 95%CI 1.71–2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR = 1.49, 95%CI 1.33–1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P P = 0.05) compared to those who died in the non-TC group. Conclusions This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed long-term all-cause mortality and its association with cardiovascular risk factors in Israeli TC survivors compared to the general population. Methods: The computerized database of Clalit Health Services, the largest healthcare fund in Israel, was used to identify individuals who were diagnosed with TC during 2001-2014 (exposed group) and age- and sex-matched individuals from the same healthcare system without thyroid disease or a cancer history (non-exposed group). Cox regression hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality were calculated by exposure status. Findings: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5,677 (10·2%) exposed patients and 1,235 individuals out of 23,962 (5·2%) non-exposed patients died. The TC survivors had an increased risk of all-cause mortality (HR=1·89, 95% CI 1·71-2·10), after adjusting for cardiovascular risk factors already present at the beginning of the follow-up. This increased risk was most pronounced in the 55- to 64-year old age group (HR=1·49, 95% CI 1·33-1·67). At the end of the follow-up, the TC survivors who died had a higher prevalence of hypertension (14·6% vs. 10·3%, P=0·002), more dyslipidemia (11·4% vs. 7·2%, P

BACKGROUND Holocaust survivors during World War II were exposed to various factors that are associated with cancer risk. The objective of this study was to determine whether Holocaust survivors had an increased risk for developing cancer. METHODS The study population included 152,622 survivors. The main analysis was based on a comparison between individuals who were entitled to compensation for suffering persecution during the war and individuals who were denied such compensation. A complementary analysis compared survivors who were born in countries governed by Nazi Germany with survivors born in nonoccupied countries. A Cox proportional hazards model was used, with the time at risk of cancer development starting on either January 1, 1960, or the date of immigration to the date of cancer diagnosis or death or the date of last follow-up (December 31, 2006). RESULTS Cancer was diagnosed in 22.2% of those who were granted compensation versus 16% of those who were denied compensation (P < .0001). Adjusting for birth cohort, sex, country of origin, and period of immigration, both analyses revealed significant increased risks of developing cancer in those who were exposed. For those who were granted versus denied compensation, the hazard ratios were 1.06 (P < .001) for all sites, 1.12 (P = .07) for colorectal cancer, and 1.37 (P = .008) for lung cancer. For those born in occupied countries versus nonoccupied countries, the hazard ratios were 1.08 (P < .001), 1.08 (P = .003), and 1.12 (P = .02), respectively. CONCLUSIONS The current results, based on a large cohort of Holocaust survivors who were exposed to a variety of severe deprivations, add to the conflicting and sparse knowledge on this issue and support the notion that this group has a small but consistent increase in cancer development. Cancer 2017;123:3335-45. © 2017 American Cancer Society.

Thyroid cancer (TC) is the most common endocrine malignancy. TC patients have a good prognosis and a low disease-related mortality rate. Since such patients are often young, they may be at a higher risk for a second primary malignancy (SPM). This study sought to determine the incidence, risk, and types of SPM between 1980 and 2011, and to assess SPM trends over time among Israeli TC patients.Data were derived from the Israel National Cancer Registry. Primary TC patients diagnosed during 1980-2009 were followed up for SPM incidence until December 31, 2011. Standardized incidence ratios (SIRs) of observed to expected SPM (based on the general population rates) were calculated using Poisson regression. Analyses were stratified by time period of initial TC diagnosis (1980-1995 and 1996-2009).A total of 11,538 TC patients were identified. After exclusion of 107 duplicate cases, records of 1032 patients with SPM were analyzed (an SPM incidence of 8.9%). SIRs for all-site SPMs were 1.23 [confidence interval 1.08-1.35] for males and 1.19 [confidence interval 1.10-1.27] for females. SIRs for tumors of the urinary system and prostate were significantly elevated in males, as were SIRs for tumors of the brain, urinary system, breast, and lung in females. Variables associated with increased risk of developing SPMs included a younger age at TC diagnosis, a shorter latency period, being born in Asia/Africa for both sexes, and being born in Israel for females. Compared with the general population, a subanalysis by TC diagnosis during 1980-1995 and 1996-2009 disclosed a higher SPM incidence for the latter time period in males and for both time periods, with a slightly higher SIR for the latter time period in females.The overall risk of SPM in Israeli TC patients was significantly greater for both sexes compared with the general population, thus identifying TC patients as a high-risk group and calling for caretakers to apply specific follow-up guidelines.

Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel. [Res Gerontol Nurs. 2015; 8(6):265–272.]

Background:Several studies have suggested that post-traumatic stress disorder (PTSD) is related to adverse health outcomes. There are limited data on PTSD and cancer, which has a long latency period. We investigated the association between World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among Jewish WWII survivors and examined whether this association was modified by exposure to hunger during WWII.Methods:We compared 65 BC patients diagnosed in 2005 through 2010 to 200 population-based controls who were members of various organizations for Jewish WWII survivors in Israel. All participants were born in Europe, lived at least six months under Nazi rule during WWII, and immigrated to Israel after the war. We estimated PTSD using the PTSD Inventory and applied logistic regression models to estimate the association between WWII-related PTSD and BC, adjusting for potential confounders.Results:We observed a linear association between WWII-related PTSD and BC risk. This association remained significant following adjustment for potential confounders, including obesity, alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and total number of traumatic life events (OR = 2.89, 95% CI = 1.14–7.31). However, the level of hunger exposure during WWII modified this effect significantly.Conclusions:These findings suggest an independent association between WWII-related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by hunger, a novel finding. Future research is needed to further explore these findings.

This manuscript provides the available data on the burden of human papillomavirus (HPV) infections and HPV-related diseases in Israel. The incidence of cervical intraepithelial neoplasia grade 3 (CIN3) among Jewish women was 17.4 per 100,000 in 2007, showing an increase since 1997. The incidence of cervical cancer was 5.3 per 100,000 Israeli Jewish women and 2.3 per 100,000 Israeli non-Jewish women in 2007. This rate is relatively low compared to other developed countries, and could be explained by cultural and religious factors such as male circumcision or sexual behavior. Mortality rates were around 1.5 per 100,000 Israeli women in 2007. Incidences of other anogenital, oral cavity, and pharynx cancers are very low, below 1.0 per 100.000 Israeli women and men. Information is scarce on HPV prevalence and HPV type distribution among women with cervical cancer. HPV types 16 and 18 were the two most common types in both preneoplastic lesions and cervical cancer, representing 60% of total invasive cases. Data on genital warts show an incidence rate of 239 per 100,000 men and 185 per 100,000 women, similar to that found in other Western countries. Despite these low incidences, it is important to improve the information on the overall burden of HPV-related morbidity and on the HPV prevalence to evaluate an organized cervical cancer screening program and the introduction of the HPV vaccine in the national school-based vaccine program. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Purpose Our goal was to describe adolescent cancer incidence and survival in Israel, and to identify demographic and epidemiologic variations among adolescents with cancer. Patients and Methods We used data from the Israel National Cancer Registry in order to examine the incidence and survival of adolescent cancer in Israeli adolescents aged 15–19 years, diagnosed during the years 1998–2009. Cases were analyzed according to sex, ethnicity and geographical region, as well as comparison to other countries in the region and other western countries. Results Among the 1,532 new cases of adolescent cancer, there was a total incidence rate of 226 cases per million. The incidence rate for males was higher than for females (230 and 222, respectively) and higher for Jewish adolescents than for Arab adolescents (235 and 194, respectively). The largest groups were Lymphomas (69 per million), Malignant Epithelial Neoplasms (49 per million), and Leukemias (21 per million). We estimated the survival probability updated to December 2009, and calculated the 5-year survival for new cases until the end of 2004. The overall survival at 5 years was 78%, with 62% for the Arabic population and 81% for the Jewish population, dependent on the diagnosis. Conclusions The results of this study show little difference in the predominance of some adolescent cancers in comparison with other developed countries. This study may add more information for further investigation of the genetic and environmental factors that cause adolescent cancer in Israel. As well as delineate the genetic basis for ethnic origin disparities in survival. Pediatr Blood Cancer 2013;60:1848–1854. © 2013 Wiley Periodicals, Inc.

Breast cancer is the most common malignancy in Israeli Jewish and Arab women. The main objective of this study was to reexamine the trends in breast cancer incidence, mortality, and survival in Israel in 1996 through 2007, as well as the use of mammography. Data were obtained from the Israel National Cancer Registry, the Central Bureau of Statistics, and National Health Surveys. Incidence and mortality rates per 100 000 are age adjusted to the world standard population. Time trends are presented using the joinpoint regression analysis. The relative survival was calculated for the diagnosis years 1996-2003. Data on mammography performance were obtained from the Knowledge, Attitudes and Practices surveys carried out in 2002-2008. From 1996 through 2007, the incidence of in-situ breast cancer increased in both subpopulations whereas the incidence of invasive breast cancer decreased by 3% for Jewish women and increased by 98% for Arab women (P value for 'between-populations' differences

Obesity has been linked to various malignancies, but a clear relation of overweight with urothelial cancer has not been established. We assessed the association between adolescent obesity and future risk for urothelial cancer. Medical data on 1,110,835 Israeli adolescents examined for fitness for military duty between 1967 and 2005 were linked to the National Cancer Registry in this nationwide population-based cohort study. We used Cox proportional hazards modeling to estimate the covariate-adjusted hazard ratio (HR) for urothelial cancer associated with BMI measured at age 17. The mean follow-up of 17.6 ± 10.8 years reflected 19,576,635 person years, during which 661 examinees developed urothelial cancer of the bladder, ureter, or renal pelvis. BMI ≥ 85 th standard percentile in adolescence significantly predicted increased risk of urothelial cancer with a HR (adjusted for year of birth, education and religiosity) of 1.42 (95% confidence interval (CI), 1.13-1.77, P = 0.002). Similar results were observed using the ≥ 25 kg/m(2) definition of overweight (HR = 1.36 (95% CI, 1.08-1.72), P = 0.008). Incidence of urothelial cancer was significantly lower in the more educated and among those who attended religious schools. Overweight in adolescence is related to increased risk of future urothelial cancer. In view of the growing incidence of both urothelial cancer and adolescent obesity, our study suggests an avenue for possible prevention of urothelial cancer.

Background and aims The relationship between exposure to petroleum products and cancer is well-established in occupational studies carried out among employees of transportation and oil-producing industries. However, question remains whether living near petroleum storage facilities may represent a cancer risk. In the present study, we examined cancer incidence rates associated with residential proximity to the Kiryat Haim industrial zone in Northern Israel, using different analytical techniques and adjusting for several potential confounders, such as road proximity, population density, smoking rates and socio-demographic attributes. Methods Both traditional zonal approaches and more recently developed Double Kernel Density (DKD) tools were used to estimate relative risks of lung and NHL cancers attributed to residential proximity to the petroleum storage site. Results Zonal approaches based on comparing ASRs across small census areas (SCAs) did not detect any significant association between residential proximity to the industrial zone and the two types of cancers under study (P > 0.2). In contrast, the DKD approach revealed that the relative density of both lung and NHL cancers declined in line with distances from the industrial zone, especially among the elderly (Lung: t > − 12.0; P − 9.0; P

Holocaust survivors during World War II were exposed to various factors that are associated with cancer risk. The objective of this study was to determine whether Holocaust survivors had an increased risk for developing cancer.The study population included 152,622 survivors. The main analysis was based on a comparison between individuals who were entitled to compensation for suffering persecution during the war and individuals who were denied such compensation. A complementary analysis compared survivors who were born in countries governed by Nazi Germany with survivors born in nonoccupied countries. A Cox proportional hazards model was used, with the time at risk of cancer development starting on either January 1, 1960, or the date of immigration to the date of cancer diagnosis or death or the date of last follow-up (December 31, 2006).Cancer was diagnosed in 22.2% of those who were granted compensation versus 16% of those who were denied compensation (P.0001). Adjusting for birth cohort, sex, country of origin, and period of immigration, both analyses revealed significant increased risks of developing cancer in those who were exposed. For those who were granted versus denied compensation, the hazard ratios were 1.06 (P.001) for all sites, 1.12 (P = .07) for colorectal cancer, and 1.37 (P = .008) for lung cancer. For those born in occupied countries versus nonoccupied countries, the hazard ratios were 1.08 (P.001), 1.08 (P = .003), and 1.12 (P = .02), respectively.The current results, based on a large cohort of Holocaust survivors who were exposed to a variety of severe deprivations, add to the conflicting and sparse knowledge on this issue and support the notion that this group has a small but consistent increase in cancer development. Cancer 2017;123:3335-45. © 2017 American Cancer Society.

SUMMARY AIM: The objective of the study was to examine the impact of WWII-related caloric restriction (CR) on subsequent breast cancer (BC) risk based on individual exposure experiences and whether this effect was modified by age at exposure. Methodology: We compared 65 breast cancer patients diagnosed between 2005‐2010 to 200 controls without breast cancer who were all members of various organizations for Jewish WWII survivors in Israel. All participants were Jewish women born in Europe prior to 1945 who lived at least 6 months under Nazi rule during WWII and immigrated to Israel after the war. We estimated CR using a combined index for hunger and used logistic regression models to estimate the association between CR and BC, adjusting for potential confounders. Results: Women who were severely exposed to hunger had an increased risk of BC (OR=5.0, 95% CI= 2.3‐10.8) compared to women who were mildly exposed. The association between CR and BC risk was stronger for women who were exposed at a younger age (0‐7 years) compared to the risk of BC in women exposed at ‡ 14 years (OR= 2.8, 95% CI=1.3‐6.3). Conclusions: Severe exposure to CR is associated with a higher risk for BC decades later, and may be generalized to other cases of severe starvation during childhood that may have long-term effects on cancer in adulthood. What’s known • The relationship between caloric restriction and cancer risk is a complex one. • Most of the studies in humans were based on hunger exposure during extreme wartime situations, not controlled caloric restriction. • Caloric exposure was assed based on geographical variables relating to the whereabouts of individuals during the time of exposure. • In a previous Israeli study, the incidence of all cancers was higher among Israeli Jews who were potentially exposed to the Holocaust than among those who were not. What’s new • We assessed individual exposure to caloric restriction based on three indices that were constructed. Though based on previously used research tools, they added novel dimensions in order to achieve a more comprehensive view of the exposures experienced by the survivors of WWII throughout the total war period. • Women who were severely exposed to hunger had an increased risk of Breast cancer. • The association was stronger for women who were exposed at a younger age. 1

There is renewed interest in flexible sigmoidoscopy (FS) colorectal cancer (CRC) screening following trials showing significantly reduced CRC incidence and mortality.To evaluate the potential usefulness of FS screening in our population.We examined rectosigmoid (RS) cancer epidemiology in our Jewish population using Israel National Cancer Registry data, computed by CRC site, age groups, and gender. We also reviewed endoscopy-screening publications for prevalence of RS and proximal advanced adenomas (AAP) and having both or either.During 1980-2008, there were 64,559 CRCs registered; 31.6 % were RS cancer which has now decreased to 29 % of men's and 26 % of women's CRC (both P0.01). In50 year olds, RS cancer occurred in 42 % of males' and 35 % of females' CRC, and in the last 2 decades this ratio is unchanged. In 50-74 year olds, RS cancer decreased to stable levels of 32 % of males' and 29 % females' CRC (both P0.01). In ≥75 year olds, RS cancer progressively decreased to 24 % of males' and 22 % females' CRC (both P0.001). From endoscopy screening reports in 40-79 year olds, RS AAPs occurred in 2.0-5.8 %, being least in women, most in men, and not increased with aging. Some 50-57 % of screenees had both RS and proximal AAPs, least when aged 40-49 years at 25 %, women were 35 %, and with aging 40 %, but most in men at 70 %.With the changing CRC epidemiology, having fewer RS neoplasms but more proximal cancer, the effectiveness of FS screening for identifying significant neoplasms decreases with screenees' age and especially in females. These make FS screening less suitable for our aging and increasingly female population.

Summary Merkel cell carcinoma (MCC) is a rare aggressive skin tumour that appears to be associated with a large number of other tumours. We collected all reported cases in Israel and estimated its association with other tumours, including haematological malignancies. The population based Israel Cancer Registry identified 335 patients with MCC diagnosed between1989 and 2010. Ninety-seven percent were in the Jewish population; median age at diagnosis for Jewish patients was 73·4 and 55·6 years for the Arab population. Other associated malignancies were encountered in 92 patients (27·4%) with MCC (90 Jews, two Arabs). Of the Jewish cases, 66 presented with an associated malignancy before, and 24 after, the diagnosis of MCC. Solid tumours were not significantly increased among patients with MCC. Thirty-one of these associated cancers (34·4%) were haemato-oncological malignancies, 24 were detected before and seven after the diagnosis of MCC. The standardized incidence ratio (SIR) for haematological malignancy was 3·67 for males and 3·62 for females, and the most frequent haemato-oncological neoplasias recorded were chronic lymphocytic leukaemia (45%) and lymphomas (29%). Although MCC is rare, clinicians should be aware of the possible association with B-cell lymphoproliferative disorders when evaluating patients with neuroendocrine skin tumours.

The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with pancreatic cancer incidence in a cohort of 720,927 Jewish Israeli men. Body mass index (BMI) was measured during a general health examination at ages 16–19 between the years 1967 and 1995. Overweight was defined as BMI ≥ 85th percentile of the reference US-CDC distribution in adolescence. Pancreatic cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 23.3 ± 8.0 years. During 16.8 million person-years, 98 cases of pancreatic cancer were detected. Using Cox proportional hazards modeling, overweight in adolescence predicted an increased risk of pancreatic cancer [hazard ratio (HR) = 2.09; 95% confidence interval (CI): 1.26–3.50, p = 0.005]. Compared with adolescents with ‘normal’ range BMI Z-scores (−1 to +1), adolescents with Z-scores > 1 showed significantly increased risk [HR, 2.28 (95% CI: 1.43–3.64), p = 0.001]. Lower education level (10 or less years of schooling vs. 11–12 years) was also associated with increased risk of pancreatic cancer [HR 1.90 (95% CI: 1.27–2.86, p = 0.002)], whereas height, country of origin and immigration status were not. Adolescent overweight is substantially associated with pancreatic cancer incidence in young to middle-aged adults. Applying our point estimates to the 16.8% prevalence of excess weight in Israeli adolescents in the past decade suggests a population fraction of 15.5% (95% CI: 4.2–29.6%) for pancreatic cancer attributable to adolescent overweight in Israel.

Objectives This study explored cancer incidence rates in a large cohort of Israeli (Jewish and Arab) opioid-dependent individuals receiving methadone maintenance treatment (MMT), and how the incidences vary by ethnicity and sex. Method The record linkage between the Israel National Addiction Registry (INAR) and the Israel National Cancer Registry (INCR) was performed. Information about the Israeli general population from the Central Bureau of Statistics was used for comparison to match sex and year of birth to the cohort under study. Age standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. Results Though the SIR values for aggregated cancer sites for both men and women on MMT did not differ significantly from the corresponding figures in the general population (0.88, 95% CI 0.76–1.00, and 1.06, 95% CI 0.76–1.36, respectively), the risks were substantially increased for lung (1.97, 95% CI 1.13–2.82), larynx (3.62, 95% CI 1.11–6.13) and liver (6.8, 95% CI 1.76–11.83) cancers among Jewish men and for cervix uteri cancer among Jewish women (2.41, 95% CI 0.99–3.84). By contrast, the SIR values for colorectal cancer among Jewish men (0.46, 95% CI 0.09–0.82) and for breast cancer among Jewish women (0.36, 95% CI 0.00–0.71) were significantly lower than expected. Conclusions The results suggest that the increased and reduced site-specific cancer risks are counterbalanced, resulting in the absence of the expected excess cancer risk for the entire cohort. The reduced risks for colorectal and breast cancers suggest a protective effect of MMT, warranting further investigation.

Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥ 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17–2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38–1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26–2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33–2.3, P < 0.001)]. Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. Cancer Epidemiol Biomarkers Prev; 20(12); 2524–31. ©2011 AACR.

Purpose To assess whether radiation therapy for prostate cancer (PCa) increases the risk of metachronous rectal cancer (RCa) and compare outcomes of RCa after radiation therapy and surgery. Patients and methods The Israel Cancer Registry was queried to identify patients with PCa and RCa diagnosed between 1982 and 2005. The age adjusted standardized incidence ratio (SIR) of RCa was defined as the ratio between the observed and expected (calculated) RCa cases and compared among the following: overall Israeli male population, patients with PCa treated with radiation therapy, patients with PCa treated surgically. The medical records of men diagnosed with RCa were reviewed and clinical characteristics retrieved. Results Of 29,593 men diagnosed with PCa, 2163 were treated with radiation therapy, 6762 were treated surgically and 20,068 patients were treated with either primary androgen deprivation therapy or offered watchful waiting. Of the entire study cohort, 194 (0.65%) patients were diagnosed with subsequent RCa. Compared to the overall male population and stratified by treatment modality, the risk of developing RCa after radiation therapy was significantly increased (SIR = 1.81, 95% CI 1.2-2.5), whereas it was not increased in those managed by surgery (SIR = 1.22, 95% CI 0.85-1.65). RCa after radiation therapy was diagnosed at a more advanced stage, translating into inferior disease specific survival. Conclusions Compared to men diagnosed with PCa managed by surgery, we observed an increased risk of RCa in patients treated with radiation therapy. Further studies are needed to validate these findings and assess whether routine colonoscopic surveillance is warranted after pelvic radiation.

Objective To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake. Setting The Clalit Health Service screening programme, Israel. Methods Average-risk individuals aged 50–75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSA™ (3 evacuations) and FIT with the OC- MICRO™ (3 evacuations, refrigerating mandated). The GLIMMIX model was used. Results There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73–2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24–0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46–2.17], P = 0.99). Conclusions Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated.

OBJECTIVES: Most colorectal cancer (CRC) screening guidelines recommend average-risk screening up to the age of 75 years. However, increasing life span and incidence of proximal CRC could require changes to the age guidelines and adapting screening methodology for the elderly persons. Therefore, we reviewed our CRC epidemiology, international screening age-guidelines, and screening tests for the elderly persons and presented our long-term results of colonoscopy and semi-quantitated immunochemical fecal occult blood tests (I-FOBTs) in individuals that are 75 years or more. MATERIALS AND METHODS: We examined the Israel National Cancer Registry (INCR) data to assess the risk of CRC in individuals aged 75 years or more. We re-examined files of patients aged 75 years or more, who underwent both colonoscopy and three I-FOBTs, and followed them through the INCR to identify new cases of CRC. RESULTS: Nationwide, during 2005 and 2007, 41.3% of all CRCs occurred in individuals aged 75 years or more. Both I-FOBT and colonoscopy were performed on 271 individuals (mean age: 78.5 years, standard deviation: 3.1). Both initial colonoscopy and I-FOBT of at least 50 ngHb/ml buffer in either of the first two tests identified six patients with CRC; INCR registered another stage 1 rectal CRC within 1 year. Therefore, the initial sensitivity to CRC of either test was 85.7% (95% confidence interval: 59.8 and 112), valid during a mean of 44.3 months and a standard deviation of 13.4 at INCR follow-up; 14 of 27 advanced adenomatous polyps were identified by I-FOBT, giving a sensitivity of 58.8% (95% confidence interval: 42.3 and 75.4) for CRC or advanced adenomatous polyps. CONCLUSION: Recently, 41.3% of our CRCs occurred in individuals aged 75 years or more, diagnosed clinically and not by screening. I-FOBT and initial colonoscopic CRC sensitivity were similar, both having false-negative results. Screening age guidelines need reconsideration; our initial results show that semi-quantitated I-FOBT screening is feasible but needs large-scale evaluation in 'healthy' elderly persons.

The risk of melanoma is higher in patients with Parkinson's disease (PD) than in the general population. Whether the association is disease related or treatment related is unclear. The objective of this study was to assess melanoma prevalence in PD patients in Israel using active dermatologic screening. Consecutive patients with idiopathic PD were recruited by 12 Israeli centers. A movement disorder specialist assessed the severity of PD and obtained a medical, neurological, and medication history. Subsequently, a dermatologist assessed melanoma risk factors, recorded a dermatologic history, proactively performed a whole-body skin examination, and biopsied suspicious skin lesions. Of the enrolled patients (n = 1,395, mean age 69.5 ± 10.6 years, mean PD duration 7.3 ± 6.0 years), 95.3% were treated with dopaminergic agents. Biopsies revealed 8 patients with melanoma in situ and 1 with invasive malignant melanoma; 14 patients reported a melanoma prior to enrollment. The observed 5-year limited duration prevalence of melanoma in PD patients was 4.4 times greater (95% CI 2.6-7.6) than expected from melanoma prevalence in an age- and sex-matched cohort from the Israel National Cancer Registry. The increase was accounted for by an elevated prevalence of melanoma in situ [relative risk 12.5 (95% CI 6.7-23.2)]. Occurrence of melanoma did not correlate with levodopa therapy or time of onset of PD. Melanoma prevalence in PD patients was higher than expected in the general Israeli population. This was not related to levodopa treatment. PD patients should be actively screened for melanoma on a routine basis.

In many countries at risk for colorectal cancer (CRC), screening guidelines provide average-risk screening for patients aged between the ages of 50 and 75 years. However, an earlier onset of CRC, an increasing life span and an incidence of right-sided CRC have been noted, which could require changes in age guidelines and screening methodology, especially for the elderly. We examined this in our Jewish populations using Israel Cancer Registry data, 1980-2008, computed by age groups, sex, ethnic groups, cancer site, and cancer stage. In patients who were below 50 years of age, there was no significant increase in incidence except for men born in Israel (P=0.05). In patients aged between 50 and 74 or more than 75 years there was an increased incidence (P

Objective Cancer risk in the elderly is about ten-fold higher than in younger age groups. Although several risk factors have been associated with cancer incidence among the general population, little is known about cancer risk factors among individuals entering old age without evidence of disease. Material and methods A historic cohort study of an age homogenous representative cohort of community-dwelling subjects born 1920–1921, enrolled in the Jerusalem Longitudinal Study. Subjects were aged 70 at baseline (1990) and underwent comprehensive assessment of numerous domains. Cancer incidence from age 70 to 88 (1990–2008) was ascertained from the Israel Cancer Registry. Results The cohort included 435 persons free from cancer at 1990 and the median follow-up was 16.1 years. Malignancies occurred among 59 persons (13.6%). Using Cox regression multiple analyses, diabetes mellitus (HR = 2.28, 95% CI: 1.27–4.09) and smoking pack years (HR = 1.01 per year, 95% CI: 1.001–1.022) were associated with increased risk of developing cancer after controlling for sex. On the other hand, gender, poor self-rated health, lower educational level and physical inactivity were not associated with cancer. Conclusions Diabetes mellitus and smoking pack years at age 70 are associated with an elevated risk of developing cancer. The possibility of detection bias in the association of diabetes mellitus with the risk cancers cannot be ruled out.

The age-standardized incidence rate (ASR) of invasive cervical cancer in Israeli-Jewish women is persistently low compared to many other countries. The aim of the present study was to assess selected demographic characteristics of Israeli-Jewish women with cervical squamous cell carcinoma (SCC) in an attempt to identify current selected risk factors. Included were all histologically confirmed SCC patients diagnosed during 2002–2004 according to the Israel National Cancer Registry. Demographic and population data were obtained from the Central Population Registry and from the Israel Central Bureau of Statistics annual abstract reports. The ASR and incidence rate for each demographic category were computed. During the study period, 350 SCC patients (mean age 50.3 years) were diagnosed (ASR of 3.8/100,000). High SCC incidence rates of single women 40+, of married women 30+ years old and of divorced and widowed women in the 40–49 age group were found. The mean number of children was 2.1 (range 0–9). Compared to the population the rate of childless patients in the 50+ age group, that of patients with 1–2 children in the 40–49 age group and that of North-African-born patients was significantly higher. No excess rate was found for multiparity and low socioeconomic status. High incidence rates of SCC were observed for some age groups of single and married women, for women without children or 1–2 children and for North-Africa-born women. Great differences between age groups within each demographic category were observed.

Studies comparing brain tumor incidence have consistently shown lower incidence in Africans compared to European populations. We compared the incidence of brain tumors in Ethiopian immigrants and their Israel-born descendants with other Israeli subpopulations. We included all cases of benign or malignant brain tumors from 1992 to 2003, as reported to the Israel Cancer Registry, except individuals known to have been irradiated for tinea capitis. Age standardized incidence rates (ASR) and standardized incidence ratios (SIR) were calculated. Among Ethiopian-born immigrants, 38 brain tumors were diagnosed (an ASR of 6.68 per 10(5) for all brain tumors among Ethiopian immigrants). The incidence of all brain tumors and malignant brain tumors among Ethiopian immigrants was significantly lower than that in Israeli-born Jews [SIR = 0.73, 95% confidence interval (CI) 0.50-0.96, and SIR = 0.65, 95% CI 0.32-0.98, respectively] and in all other Jewish subpopulations. Brain tumor incidence was not significantly different in Israeli-born children of Ethiopian immigrants aged 0-14 compared to Ethiopian immigrants of the same age group (SIR = 0.68, 95% CI 0.14-1.23), and was comparable to incidence among Israeli children of non-Ethiopian parents. We concluded that ethnicity influences brain tumor incidence, and that Ethiopian immigrants to Israel appear to be protected. If an environmental influence on the protective effect of the Ethiopian population in Israel exists, it was not demonstrated in the study in a statistically significant manner. Further investigation is needed to understand the factors involved in the incidence variation among different populations.

The Incidence of colorectal cancer (CRC) differs in different ethnic groups. The aim of this study is to investigate clinical and pathological features of CRC in Arab as compared to Jewish patients in Northern Israel. Clinical and pathological characteristics of 480 patients with CRC treated between 1999 and 2006 were retrospectively reviewed. Eighty-five percent of the patients were Jews and 15% were Arabs. Mean age at diagnosis was 67.1 years in Jews and 58.3 years in Arabs (P < 0.001). Stage I CRC was 17.5% versus 7.2% (P < 0.05), Stage II was 35.5% versus 27.5% (P < 0.01), Stage III was 26% versus 33.3% (P:0 < 0.01) and Stage IV 21% versus 31% (P < 0.01) in Jewish and Arab patients respectively. In 40.6% of Jewish patients, cancer was well differentiated compared to 27.1% of Arab patients (P < 0.01) and poorly differentiated in 5.5% versus 10,4% (P < 0.05). Abdominal pain, constipation and weight loss were more common in Arabs than in Jews (P < 0.05). In conclusion CRC is more advanced, more aggressive and more symptomatic in Arab than in Jewish patients. Arab patients are younger at the time of diagnosis. Screening for CRC should be started at earlier age in the Arab population than the population at large.

A population-based study of cervical intraepithelial neoplasia grade 3 (CIN3) has hitherto not been performed in Israel. The aim of the present study was to assess selected demographic characteristics of Israeli Jewish CIN3 patients in an attempt to identify the risk factors in this population.All CIN3 patients diagnosed during 2002-2004 according to the Israel National Cancer Registry were included. Demographic and population data were obtained from the Central Population Registry and from the Israel Central Bureau of Statistics annual abstract reports. The age-standardized incidence rate (ASR) and rate ratios (RR) for each demographic category were calculated.The study comprised 1,108 CIN3 patients (mean age 38.4 years) yielding an ASR of 13.9/100.000. A significantly greater number of CIN3 in the 30-39-year (RR = 2.16) and 40-49-year (RR = 1.74) age groups were observed. The overall rate of single and married women was similar, that in widowed women significantly lower and divorced women significantly higher (RR = 2.37) than in the general population. The mean number of children was 1.7. The rate of patients with 5 + children was significantly higher only in the 30-39-year age group. RR varied with age within each demographic category. The rate of Israeli born was higher and that of other ethnic origins was similar to the population rates. No association between CIN3 and socioeconomic status was found.Greater CIN3 rates were observed in women of 30-49 years, divorced women and Israeli-born women. Great differences in RR between age groups within the demographic categories were observed.

Objectives:To evaluate the incidence rates of cervical cancer by ethnic origins and compare these rates between first- and second-generation women of North African origin.Methods:Data of all cervical carcinoma of Jewish women during 2000 to 2005 were obtained from the National Cancer Registry. Standardized incidence ratios for each ethnic origin category were calculated and compared using Poisson regression.Results:During the study period, 938 patients were examined. The standardized incidence ratios of North African-born women and of Israeli-born women of North African descent were significantly higher compared with those of women of other origins.Conclusions:The persistence of a higher risk of cervical cancer in Israeli Jewish women of North African descent compared with those of other origins may suggest that genetic factors are involved in the etiology of this neoplasm.

In the absence of patient-specific data, composite level data are often used in epidemiological studies. However, since individual exposure levels cannot accurately be inferred from aggregate data, such an approach may lead to erroneous estimates of health effects of potential environmental risk factors. In the present study, we attempt to address this information-loss problem by using the “kernel density function”, which estimates the intensity of events across a surface, by calculating the overall number of cases situated within a given search radius from a target point. The present paper illustrates the use of this analytical technique for a study of association between the geographical distributions of lung cancer cases and SO2 air pollution estimates in the Greater Haifa Metropolitan Area (GHMA). In the analysis, the results obtained by kernel smoothing are contrasted with those obtained by areal aggregation techniques more commonly used in empirical studies.

Positive direct antiglobulin tests (DATs) have been associated with both autoimmunity and lymphoproliferative disorders. However, it is unknown whether DAT+ in healthy blood donors is associated with an increased risk of malignancies.In the current study, all blood donors with DAT+ samples were identified during the years 1999 through 2003 through the Magen David Adom National Blood Services in Israel. This study compared the risk of cancer among 586 DAT+ and 2344 DAT- donors who were matched according to sex, age, and year of donation. The risk of cancer in DAT+ donors was also compared to expected rates in the general Israeli population. Cancer was ascertained through the Israel Cancer Registry.Malignancies occurred among 17 (2.9%) of the DAT+ and 27 (1.2%) of the DAT- blood donors; of these, 3 donors in the DAT+ group were diagnosed with hematopoietic malignancies within 12 months of their donation. Even after excluding these early cases, the relative risk of developing cancer was 2.14 (95% confidence interval [CI], 1.13-4.10) comparing DAT+ with DAT- donors, while the relative risk for hematopoietic cancer was 8.3 (95% CI, 1.5-43.2). Comparing DAT+ blood donors with the general population, the standardized incidence ratios (observed/expected cases) were elevated at 2.11 (95% CI, 1.15-3.54; p = 0.16) for all malignancies and 8.03 (95% CI, 2.2-20.6; p = 0.003) for hematologic malignancies.There is evidence of a significantly increased risk of cancer, especially hematologic malignancies, among blood donors with a positive DAT even within a short follow-up period.

Background Several epidemiological studies explored the risk for cancer among both persons with schizophrenia and their first-degree relatives, and among patients with bipolar disorder. No studies have yet explored the risk among persons with schizoaffective disorders. Method Linkage analysis was conducted based on the psychiatric and the cancer national databases. Standardized incidence ratios (SIR) for aggregated cancer sites were calculated by comparing the incidence rates among patients in the psychiatric case register with schizoaffective disorders with the incidence rates in the Jewish–Israeli general population. Results No significant alteration in cancer risk was found for both genders: males, SIR = 1.11, 95% CI (0.48–1.73) and females, SIR = 1.38, 95% CI (0.96–1.80). Limitations Our sample was derived from patients with a history of psychiatric hospitalization. Putative factors such as diet, smoking and medications were not investigated. Conclusions Our study showed no significant increase in the risk for cancer in schizoaffective disorders. Those results appear to be positioned between the schizophrenia findings that show a lower risk for cancer and the bipolar disorder findings that show an increased risk.

To assess the trend over time of the relative frequency and incidence of adenocarcinoma (AC) in Israeli Jewish women.Register study.Israel National Cancer Registry.All cases of histologically proven invasive cervical cancer diagnosed during two time periods: 1961-1971 and 2002-2004.Calculation of frequencies and incidence rates and comparison by the chi2 test and by the Poisson regression model, respectively.Frequency and incidence of AC.There were a total of 532 women with a diagnosis of cervical cancer during the first and 434 women during the second period (incidence 4.2 and 4.7/100,000, respectively). The total incidence rates and frequency rates of AC during the two periods were statistically not different. The frequency rate of AC during the second period was significantly higher in the 20-29 and the 40-49 age groups and in the North African born than in the other ethnic groups.Our study indicates that except in certain age and ethnic groups, the frequency and incidence of AC has not significantly altered in Israel over the time periods studied.

Lung cancer in Israel has previously appeared to be less common than expected, relative to the prevalence of smoking. The objective is to examine trends in lung cancer rates and smoking prevalence in Israeli Arab and Jewish men compared with the United States. Age-adjusted lung cancer incidence and mortality rates in Israel were calculated for 1980-2004 using the National Cancer Registry, and compared with the United States' rates, on the basis of the Surveillance Epidemiology and End Results program. Smoking rates were obtained from national surveys carried out during the years 1970-2004. During the period 1980-2004, among Israeli Arab men, there was an increase in lung cancer incidence rates, particularly during 1990-2004, when they increased by 17.8%. During the latter period, the incidence of lung cancer among Israeli Jewish men and men in the United States declined by 5.2 and 22.8%, respectively. In 2003-2004, the age-adjusted smoking rates were 41.3 and 31.6% among Israeli Arab and Jewish men, respectively, and past smoking habits reflect higher rates among Arab men over the past three decades. The marked increase in the incidence of lung cancer among Israeli Arab men during the last decade, without any evidence of increased smoking prevalence, might reflect a gradual loss of some apparent protection in this subpopulation. The possible explanations are changes in lifestyle, particularly in dietary habits.

In Israel, breast cancer is the most common malignancy in women, but there are large intra-population differences. The aim of this study was to compare the incidence and mortality, incidence to mortality rate ratio and stage at diagnosis of breast cancer between Arab and Jewish women in Israel. Data on all cases of breast cancer, stage at diagnosis and mortality were obtained from the National Cancer Registry and the Central Bureau of Statistics. Trends in age-specific and age-adjusted incidence and mortality rates, rate ratios and stage at diagnosis were examined for Arab and Jewish women during 1979-2002. Five-year survival rates for 1995-1999 were compared by stage. Among Arab women, age-adjusted incidence rates increased by 202.1%, from 14.1 per 100,000 in 1979-1981 to 42.6 in 2000-2002. Among Jewish women, the rates increased by 45.7%, from 71.1 per 100,000 women in 1979-1981 to 103.6 in 2000-2002. Incidence to mortality rate ratio increased for both population groups, but it is still lower among Arab women. In every age group, Arab women were more likely to be diagnosed at a more advanced stage of the disease. The rise in breast cancer incidence and mortality rates and the later stage of diagnosis among Arab women emphasize the urgent need for increasing early detection of breast cancer in the Arab population by improving rates of compliance with screening mammography.

BackgroundA reduced risk of cancer has been noted among people with schizophrenia. Given that genetic causes have been proposed as an explanation of this finding, one would expect that the risk of cancer among first-degree relatives would be equally reduced.AimsTo investigate the risk of cancer among the biological parents and full siblings of people receiving in-patient care for schizophrenia.MethodLinkage analysis was conducted between national population, psychiatric and cancer databases. Standardised incidence ratios for all cancer sites were calculated by comparing the incident rates among first-degree relatives with national incidence rates.ResultsA reduced cancer risk was found across all groups examined. Among parents, whose numbers were adequately large, the findings reached statistical significance. For index cases and siblings – a markedly younger population – only a trend was elicited.ConclusionsThe genetic hypothesis – namely, the presence of a gene with the dual effect of reducing the cancer risk and disrupting neurodevelopment – is a plausible explanation for these findings.

Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring. The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 –1976 and their offspring (n = 88,829). After linking identification numbers with Israel’s Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval. By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was ≤3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring’s or mother’s diagnosis was first (P

In social and environmental sciences, ecological fallacy is an incorrect assumption about an individual based on aggregate data for a group. In the present study, the validity of this assumption was tested using both individual estimates of exposure to air pollution and aggregate data for 1,492 schoolchildren living in the in vicinity of a major coal-fired power station in the Hadera region of Israel. In 1996 and 1999, the children underwent subsequent pulmonary function tests (PFT), and their parents completed a detailed questionnaire on their health status and housing conditions. The association between children's PFT results and their exposure to air pollution was investigated in two phases. During the first phase, PFT averages were compared with average levels of air pollution detected in townships, and small census areas in which the children reside. During the second phase, individual pollution estimates were compared with individual PFT results, and pattern detection techniques (Getis-Ord statistic) were used to investigate the spatial data structure. While different levels of areal data aggregation changed the results only marginally, the choice of indices measuring the children's PFT performance had a significant influence on the outcome of the analysis. As argued, differences between individual-level and group-level effects of exposure (i.e., ecological or cross-level bias) are not necessary outcomes of data aggregation, and that seemingly unexpected results may often stem from a misguided selection of variables chosen to measure health effects. The implications of the results of the analysis for epidemiological studies are discussed, and recommendations for public health policy are formulated.

Background It has been implied that the incidence of malignant disorders is increased in patients with non-neuronopathic (type I) Gaucher disease. The purpose of the study was to ascertain numbers of cancers in type I Gaucher disease since this is of considerable concern to patients and physicians. Methods Records of 505 patients with type I Gaucher disease seen at a large referral clinic since 1990 were culled in December 2004 to ascertain diagnosis of a cancer identified during follow-up. Age-matched data from the Israeli National Cancer Registry (INCR) database were used for comparison. Findings Patients diagnosed with cancer before 1990 were not included. Of the remaining 500 patients, 227 (45.4%) were male, mean age = 38.7 years; and 273 (54.6%) were female, mean age = 37.0 years (SD = 21.0 years for both). Twenty patients (4.0%) had developed a cancer through December 31, 2003: 6 were male and 14 were female. The most common were three cases each of lymphoma and myelodysplastic syndrome and two cases of multiple myeloma. There was no statistically significant excess of cancer rate among patients relative to age-matched rates reported in national Jewish Israeli and Ashkenazi Jewish Israeli registry records. Conclusions There appears to be no excess risk for hematological or other cancers among patients with type I Gaucher disease relative to the overall Jewish population matched for age. This study confirms recent international studies of patients with Gaucher disease for no excess risk for all cancers but multiple myeloma where these latter studies implicate a significantly higher incidence.

Studies exploring the relationship between schizophrenia and cancer have shown conflicting results. Our study explores this association in three Jewish-Israeli population groups defined by their continent/place of birth (Israel, Europe-America, and Africa-Asia). The identification of the patients was made through the linkage of the nationwide psychiatric and cancer registries. The incidence of cancer in patients diagnosed with schizophrenia was compared with the incidence in the general population. The results showed that the cancer standardized incidence ratios (SIRs) for all sites were significantly lower among men and women with schizophrenia, 0.86 [95% confidence interval (CI) 0.80-0.93] and 0.91 (95% CI 0.85-0.97), respectively. This reduced overall risk was clearest for those born in Europe-America, both men (SIR 0.85, 95% CI 0.74-0.97) and women (SIR 0.86, 95% CI 0.77-0.94). Among women diagnosed with schizophrenia, the SIR was statistically higher for cancer in the breast among those born in Asia-Africa (1.37, 95% CI 1.12-1.63) and in the corpus uteri among the Israel-born (2.75, 95% CI 1.69-3.81) than among their counterparts in the general population. Lung cancer was significantly higher in men born in Asia-Africa diagnosed with schizophrenia than in the respective comparison population group (1.58, 95% CI 1.13-2.2). Our findings, and those of the literature, justify conducting a multinational study that includes identification of cancer-related risk factors among patients with schizophrenia and their families, and information on the use of psychotropic medications. This effort may clarify an epidemiological puzzle that remains outstanding.

Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in Israel for the period between 1960 and 1998 were analysed. World standardised incidence rates of 20.7 and 7.5 per million among men and women, respectively, were calculated. The highest incidence rates were displayed by men originated from Africa and by Asian-born women.

Objective: To evaluate the risk for developing second primary thyroid cancer (TC) following breast cancer (BC) and second primary BC following TC on a nationwide basis. Methods: All BC and TC Jewish females diagnosed in Israel during 1960–1998 were identified through the Israel Cancer Registry. The expected second primaries were calculated using cancer incidence rates stratified by age, country of birth and period of diagnosis among the Jewish population in Israel. Standardized incidence ratios (SIRs) were estimated using Poisson regression. Results: A total of 49,207 breast and 4911 thyroid neoplasms were identified. After the exclusion of concomitant disease (diagnosed within 1 year), 59 and 70 second primaries TC and BC yielded SIRs of 1.34 (95% CI: 1.03, 1.72) and 1.07 (95% CI: 0.84, 1.34), respectively. Younger age and earlier calendar year of first primary diagnosis and shorter follow-up period were associated with increased risk for developing second primary neoplasm. Conclusions: Considering the long latency required for carcinogenesis, excess risk of second primary diagnoses soon after the first cancer, argues against the hypothesis of first primary treatment as an initiator for the second cancer. A detection bias of meticulously followed cancer patients, early exposure to common risk factors or genetic susceptibility of certain subpopulations for both malignancies seem plausible.

Physicians' occupational environment includes exposures to potential carcinogenic factors on a regular basis. The prevalence of specific tumor types and subsequent mortality are reported to be elevated in physicians.To assess the incidence of various cancer types among Israeli physicians of various specialties, as compared with the general population, and to determine the role, if any, of gender and ethnicity.This historical retrospective cohort analysis incorporated data on Israeli officially licensed physicians and information retrieved from the Israel National Cancer Registry database (INCR). Physicians were divided into five groups: non-specialists, internists, pediatricians, surgeons, and potentially at-risk specialties. Data were collected retrospectively for the years 1980-2007.The study cohort comprised 37,789 physicians, of whom 33,393 (88.37%) were Jews and 4396 (11.63%) were Arabs. Comparing Jewish physicians to the general population revealed higher rates of: a) breast cancer among female specialized physicians, and b) melanoma among specialized male and female physicians. All cancer types were more prevalent in the Arab physicians than in the general Arab population.This study revealed incidences of specific cancer types among different medical specialties as compared to the general population. Hopefully, these findings will prompt changes in the occupational environment of physicians of particular specialties in order to reduce their high risk for cancer occurrence.

Data on adolescent precursors of thyroid cancer in adulthood are scant.In order to evaluate potential risk factors for thyroid cancer, we linked two national data sources: the military recruitment health examinations and the Israel National Cancer Register. The study population (1,624,310 participants) included 1,145,865 Jewish males aged 16-19 years when examined between 1967 and 2005, and 478,445 Jewish females aged 16-19 years when examined between 1989 and 2005. The cancer follow-up extended up to 2006. Multivariable Cox proportional hazards modeling was used.During 24,389,502 person years of follow-up, 760 incidence cases of thyroid cancer were identified. The mean age at diagnosis was 25.2±4.2 years for women and 37.2±10.0 years for men. Women had a substantially higher incidence (birth cohort-adjusted hazard ratio (HR)=5.70 [95% CI 4.45-7.31]; p0.001). Height predicted incidence in both sexes, with birth cohort-adjusted HRs of 1.03 (p0.001) in males and 1.04 (p0.001) in females, per 1 cm increment in height. In males, but not in females, there was a graded association between education, as measured by years of schooling, and incidence of thyroid cancer. Body mass index was not associated with incidence. In a multivariable analysis of 617,613 males and 469,185 females examined from 1989 onwards, which included sex, birth year, height, and education, the excess risk in females persisted strongly (HR=5.67 [CI 4.30-7.13]), as did the association with height.Female sex, measured height in adolescence, and later birth cohorts were independent predictors of thyroid cancer in young and middle-aged adults in Israel. Further study is needed to unravel the mechanisms whereby height is associated with thyroid cancer.

Background: Following research demonstrating an increased risk for meningiomas in the Jewish population of Shiraz (Iran) we conducted a cohort analysis of meningiomas among Jews originating in Iran and residing in Israel. Materials and Methods: We use the population-based registry data of the Israeli National Cancer Registry (INCR) for the main analysis. All benign meningioma cases diagnosed in Israel from January 2000 to the end of 2009 were included. Patients that were born in Iran, Iraq, Turkey, Bulgaria and Greece were used for the analysis, whereby we calculated adjusted incidence rates per 100,000 people and computed standardized incidence ratios (SIRs) comparing the Iranian-born to each of the three other groups. Results: Iranian-born Jews had statistically significant higher meningioma rates rates compared to other Jews originating in Balkan states: 1.46 fold compared to Turkish Jews and 1.86 fold compared to the Bulgaria-Greece group. There was a small increase in risk for the Iranian born group compared to those who were born in Iraq (1.06, not significant). Conclusions: Higher rates of meningiomas were seen in Jews originating in Iran that are living in Israel as compared to rates in neighboring countries of origin. These differences can be in part attributed to early life environmental exposures in Iran but probably in larger amount are due to genetic and hereditary factors in a closed community like the Iranian Jews. Some support for this conclusion was also found in other published research.

OBJECTIVES To determine the incidence of ovarian malignant tumors in childhood and adolescence, to ascertain the frequency distribution of the various tumor types and to assess time trends in Israel on a nationwide basis. METHODS The study group included all Israeli Jewish patients < or = 19 years old with histologically confirmed ovarian malignancies, diagnosed in Israel from 1970 to 1994. Data were obtained from the Israel Cancer Registry. The effects of age at diagnosis and period of diagnosis were analyzed using the Poisson regression. RESULTS Among the 82 patients identified, the most frequent tumors (72.0%) were of germ cell origin and among those about one third were dysgerminomas. Epithelial tumors were diagnosed in 26.6% of the patients and most of these were borderline malignancies. The incidence rate (IR) for the total group of ovarian malignancies in the 0-19 age group was 0.52 and for ages 5-19 it was 0.71 per 100,000. After adjustment for age, a significant linear trend for a decrease of germ cell tumors over time was found, stemming from a decrease of dysgerminomas. A significant trend for increase in the IRs with age was also found. In addition, a steep rise in the age specific IRs of epithelial borderline tumors was noted in the last 5 year period. CONCLUSIONS The IRs of ovarian malignancies in childhood and adolescence in Israel, as in other countries, is very low as compared to adults and the most common tumors are of germ cell origin while malignant epithelial tumors are very rare. A time period effect in the germ cell tumors that resulted from an inexplicable significant decrease in the age specific IRs of dysgerminomas, was observed. A significant increase in borderline tumors was also noted and may be attributed to greater awareness of pathologists to this entity.