Israel Cancer Registry Research Articles

DOP72 The association of anti-tumor necrosis factor and thiopurine therapy with the risk of lymphoma among Inflammatory Bowel Disease patients: A nation-wide study from the epi-IIRN

Abstract Background To clarify the risk of lymphoma in patients with inflammatory bowel diseases (IBD) exposed to anti-tumor necrosis factor (anti-TNF) and/or thiopurines we aimed to evaluate the Israeli IBD population. Methods A nested case-control study on the epidemiology cohort of the Israeli IBD Research Nucleus (epi-IIRN) including all 4 Health Maintenance Organizations in Israel linked to the Israeli Cancer Registry. Patients diagnosed since 1.1.2005 until 31.12.2015 (42,954 patients) were included and followed until 31.12.2017. Each lymphoma case was matched to 30 non-lymphoma IBD patients by age, gender, IBD subtype, and date of earliest evidence of IBD in the database. Patients with other risk factors for lymphoma, or lymphoma diagnosis prior to IBD diagnosis were excluded (figure 1). Conditional logistic regression was used to compute the association of drug exposure (anti-TNF, thiopurines and combination) with diagnosis of lymphoma. Patients without exposure to anti-TNF and/or thiopurines in each group served as reference within each group. Additionally, sub-group analyses by gender, age group at inclusion (≤48, 49–64, ≥65), time from last drug exposure (≤90 days, 91–365 days, >365 days) were done. Results The final nested cohort included 5556 IBD patients (185 lymphoma cases matched to 5,371 without lymphoma). Mean follow-up (F/U): 5.5±3.5 years, 50% with Crohn’s disease, mean age at database entry 52.6±17.80 years. Anti-TNF-only exposure was documented in 4.3% (8/185) of lymphoma cases vs. 2.6% (145/5,371) of controls OR 1.97, CI 0.93–4.16, p=0.07; in males the ORs were 2.84 (CI 1.17–6.92 p=0.04) and increased to OR 3.48 (CI 1.55–7.88, p=0.002) for males <48 years and OR 2.87 (CI 1.53–5.37, p=0.001) for patients with last exposure ≤90 days (figure 2). Exposure to combination anti-TNF+thiopurines occurred in 8.6% (16/185) of lymphoma cases vs. 5.3% (282/5,371) of controls OR 2.09 (CI 1.17–3.73, p=0.013). Males on anti-TNF-thiopurine combination had OR of 3.42 (CI 1.37–8.52, p=0.003) and in sequential (non-overlapping exposure to both thiopurines and anti-TNFs during F/U) combination an OR of 2.74 (CI 1.02–7.35 p=0.02). Thiopurine-only exposure occurred in 15.1% (28/185) of lymphoma cases vs. 13.5% (726/5,371) of controls, OR 1.32 (CI 0.86–2.03, p=0.20). Males on thiopurines had an OR of 1.75 (CI 1.02–2.99, p=0.05). The risk increased further in males <48 years OR 2.17 (CI 1.01–4.66, p=0.047) and in males aged≥65 OR 3.50 (CI 1.55–7.82, p=0.002). Females were not at risk for lymphoma (figure 3). Conclusion This nationwide study suggests that exposure to anti-TNF therapy alone or in combination with thiopurines may be associated with an increased risk of lymphoma, but only in males, especially when last exposure occurred within 90 days.

The impact of socio-economic and environmental factors on the spatial patterns of cancer incidence in Israel: A registry-based cohort study

BACKGROUND AND AIM: Spatial methods usually used to identify geographical health risk differences. Only a few studies used semi-individual latent multi exposure approach, to investigate the socioeconomic and environmental factors that explain cancer risk spatial patterns. Our aim is to evaluate spatial clusters of cancer and to determine the impact of both socioeconomic and environmental factors on the spatial patterns of cancer incidence in Israel by applying generalized additive models (GAMs). METHODS: The current study is a registry-based cohort study. The data include the 1995 Israeli Central Bureau of statistics census (N=1,066,714) linked to the Israeli Cancer Registry data. In addition, ambient exposures were determined including: particulate matter with a diameter size that is equal to or smaller than 2.5µm, normalized difference vegetation index derived from satellite data, nitrogen oxides. We first used the global and local Morans’ I in order to identify cancer incidence clusters. RESULTS:During 17 years of follow-up (1998-2015) there were 62,049 new cancer cases among 1,022,637 participants in the 1995 census. Cancer incidence were clustered by geographical area (global Moran’s I Index =0.054, p-value0.000). Cancer clusters were located mainly in the northern district of Israel (surrounding Haifa region) and in the center part of Israel (surrounding Tel-Aviv region). CONCLUSIONS:The spatial clusters of cancer incidence in Israel can be attributed to socioeconomic and environmental risk factors. Further analysis will be conducted to evaluate the spatial associations with the socioeconomic and environmental factors using spatial modeling. KEYWORDS: socio-economic factors, environmental epidemiology, spatial statistics, particulate matter, cancer incidence, green space

Congenital Anomalies of the Kidney and Urinary Tract and Adulthood risk of Urinary Tract Cancer

IntroductionCongenital anomalies of the kidney and urinary tract (CAKUT) are the most common kidney diseases in childhood. Alterations in genes governing nephrogenesis may cause CAKUT, and in some cases may contribute to development of urinary tract (UT) tumors later in life. We aimed to assess the association between CAKUT and UT cancer in adulthood.MethodsWe conducted a population-based historical cohort study encompassing 1,510,042 recruits to the Israeli army between 1967 and 1997. CAKUT exposure was determined by army medical coding of CAKUT in childhood. Incidence of UT cancer (kidney, ureter, or bladder) was available through record linkage with the Israeli Cancer Registry. Recruits were followed from the prerecruitment assessment until cancer diagnosis, death, or study termination, in 2012. Cox proportional hazards models were constructed to estimate the hazard ratios (HRs) for UT cancer in participants with vs. without CAKUT.ResultsDuring a mean follow-up of 30.4 years, 2959 participants (2573 men and 386 women) developed UT cancer. Men with CAKUT exhibited an increased risk of UT cancer compared with men without CAKUT, yielding an adjusted HR of 1.98 (95% confidence interval [CI] 1.03-3.82). Among women CAKUT was associated with a HR of 5.88 (95% CI 2.19-15.76). Notably, upon stratification according to age of cancer diagnosis, the association between CAKUT and UT cancer was statistically significant only before 45 years of age in women and only after 45 years of age in men.ConclusionCAKUT is associated with a significantly increased risk of UT cancer, although the incidence and absolute risk remained quite low.

EPID-02. HEIGHT AND THE RISK OF MENINGIOMA

Abstract BACKGROUND Meningiomas are the most common primary central nervous system tumors. Risk factors for meningiomas including obesity, height, history of allergy/atopy or autoimmune diseases, have been previously assessed with conflicting results. We reviewed a large cohort of Israeli adolescents in order to assess potential risk factors for the development of meningiomas. METHODS This study analyzed a cohort of 2,035,915 Jewish men and women who underwent obligatory physical examination when aged 16 to 19 years, from 1967 to 2011. Meningioma incidence was identified by linkage to the national cancer registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according to sex, body mass index (BMI), height, history of allergic and autoimmune disease. RESULTS Linkage of the adolescent military database with the Israeli cancer registry identified 480 cases (152 males and 328 females) of meningioma during a follow up of 40,304,078-person years. The median age at diagnosis of meningioma was 42.1 ± 9.4 (range 17.4–62.6). On univariate analysis, only female gender (p< 0.01) and height (p< 0.01) were associated with risk for meningioma in the total study population. When stratified by gender, height remained a significant risk factor only in men. Spline analysis in the men group showed the minimum risk at a height of 1.62 meters and a statistically significant increase in the risk for meningioma at heights taller than 1.85 meters. BMI, past medical history including asthma, diabetes, and atopic and autoimmune diseases, were not associated with meningioma risk. CONCLUSION in this large population study, we found that sex and taller height in adolescent males was associated with an increased risk of adult meningioma.

P09.06 Risk factors associated with Meningioma in a Cohort of 2 Million Israeli Adolescents

Abstract Background: Meningiomas are the most common primary central nervous system tumors. Risk factors including- obesity, height, history of allergy/atopy or autoimmune diseases, have been assessed with conflicting results. In this study, we reviewed the database of a large cohort of Israeli adolescents in order to assess potential risk factors for the development of meningiomas. Methods: This study analyzed a cohort of 2,035,915 Jewish men and women who underwent compulsory physical examination as part of screening for army drafting between the age of 16 to 19 from 1948 to 1991. Meningioma incidence was identified by linkage to the national cancer registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according the several risk factors including sex, BMI, height, history of allergic and autoimmune disease. Results: Linkage of the adolescent military database with the Israeli cancer registry revealed 480 cases of meningioma. The median age at diagnosis of meningioma was 42.1 ± 9.4 (range 17.4–62.6). On univariate analysis, only gender (female) and height were significantly associated with the risk of meningioma for the whole study population (p<0.01 for both variables). When analyzed separately for gender- height was significant only for men. Spline analysis in the men group showed the minimum risk at a height of 1.62 meters and a statistically significant increase in the risk for meningioma at heights taller than 1.85 meters. BMI was not associated with an elevated risk of meningioma even when analyzed separately for gender. Past medical history including asthma, diabetes, and other atopic and autoimmune diseases were not found to be associated with the risk of meningioma. Conclusion: In this large population study, we found that sex and taller height in adolescent males was associated with an increased risk of meningioma.

Higher incidence of screening-related cancers in the employed population.

Employment may confound the risk of a cancer diagnosis in both directions. We hypothesized that a higher baseline rate of employment among cancer patients may explain the lack of association between a cancer diagnosis and later unemployment in many studies. To assess the unemployment rate among cancer patients before diagnosis compared with a matched cancer-free control group. Using data from the Israeli National Central Bureau of Statistics 1995 census (persons aged between 15 and 60 years old), the Israeli Tax Authority database and the Israel Cancer Registry, cancer patients (diagnosed between the years 2000 and 2007 and alive at 2011) were compared with matched cancer-free controls. There were 8797 cancer patients and 26166 cancer-free controls. We found that, in general, cancer was not associated with unemployment 2 years before diagnosis (adjusted odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.90-1.009, P = NS) after adjustment for age, gender, ethnicity, educational years and residential socioeconomic position. However, the diagnoses associated with screening (breast, prostate, colorectal and cervix cancers) were inversely associated with unemployment 2 years before diagnosis (adjusted OR = 0.90, 95% CI 0.84-0.97, P < 0.01). The results from the current study suggest that a higher baseline rate of employment among cancer patients, mainly those who were diagnosed with screening-associated cancers, explains false negative results in previous studies assessing cancer survivors' work issues.

Breast cancer among older women: The influence of age and cancer stage on survival

Purpose of studyTo describe the association between increasing age and survival among women aged over 65 years, diagnosed with breast cancer. Materials and methodsA historical prospective cohort study, comparing 3270 breast cancer patients to 13,163 non cancer age matched controls. Baseline characteristics and cancer data gathered from the Israeli Central Bureau of Statistics (1995), the Israel Cancer Registry (2000–2010). Baseline measurements included age, socioeconomic status. Cancer stage at diagnosis was clustered as stage I, stage II–III and metastatic. Cox Proportional Hazards regression models were used to determine Hazards Ratios (HR) for mortality. ResultsBetween ages 65–69 and ≥85, metastatic disease rose from 3.9% to 23.4% and stage I disease declined from 58.6% to 30.1%. At age 80–84, 50% life expectancy among controls, stage I, and stage II–III disease was 95,92 and 90 months respectively, compared to 2 months for metastatic disease. Compared to controls, between the age 65–69 to ≥85, adjusted HR’s progressively decreased among subjects with stage I from HR 0.96 (95% CI 0.69–1.33) to 0.60 (95%CI 0.36–1.01), stage II–III from HR 3.26 (95%CI2.58–4.12) to HR 1.60 (95%CI 1.22–2.09), and metastatic disease from HR 57.40 (95%CI 39.56–83.29) to HR 20.76 (95%CI 14.73–29.24). ConclusionsThis study describes the increasingly poor prognosis and short life expectancy observed among women aged ≥80 diagnosed with metastatic breast. In contrast, our findings confirm the positive prognosis associated with rising age, among older women presenting with stage I breast cancer, among whom survival was similar, if not slightly better, than non-cancer age matched controls.

Unemployment Risk and Decreased Income Two and Four Years After Thyroid Cancer Diagnosis: A Population-Based Study.

Thyroid cancer (TC) often occurs in relatively young patients and has a high cure rate. However, decreased psychological and physical well-being may reduce the work capability of patients with TC. This study aimed to compare the risk for unemployment and decreased income in TC survivors with a matched non-cancer group at two and four years after diagnosis. The study also aimed to predict unemployment and income changes at two and four years after diagnosis. A historical prospective study design was used, with cohort inception and baseline measurements drawn from the Israeli Central Bureau of Statistics 1995 National Census, with follow-up until 2011. Cancer incidence was obtained from the Israel Cancer Registry, and employment status from the Tax Authority. A matched group was sampled from the census population. Binary logistic regression analyses were used to assess odds ratios (OR) for the study outcomes, controlled for age, sex, ethnicity, education years, socioeconomic position, and employment status at two years before diagnosis. In total, 417 cases of TC and 1277 non-cancer matched subjects were included in the study. People who died during the study period were excluded. The mean age at the time of cancer diagnosis was 43.5 years in the TC group and 43.8 years in the control group (p = 0.6). After adjusting for potential confounders, a positive association was found between TC and risk of unemployment two years after diagnosis (OR = 1.46 [confidence interval (CI) 1.09-1.95]), and decreased income two years after diagnosis (OR = 1.61 [CI 1.23-2.01]) and four years after diagnosis (OR = 1.63 [CI 1.25-2.13]). The association between TC and unemployment at four years after diagnosis weakened and lost significance (OR = 1.30 [CI 0.98-1.72]). TC survivorship was associated with unemployment at two years and decreased income at two and four years after diagnosis. Decreased income may be a marker for a shift to part-time work rather than a return to full-time work. The findings suggest that interventions to enhance the return to full-time work are needed in this population.

Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964-2008.

BackgroundSocioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women.MethodsResidents of Jerusalem who gave birth between 1964–1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband’s occupation and the woman’s education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin.ResultsIn multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend.ConclusionsSEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities.

Unemployment risk and income change after testicular cancer diagnosis: A population-based study

BackgroundAmong patients with cancer, returning to full working may serve as an indicator for return to normal lifestyle following illness, as opposed to unemployment or shifting to part-time work. The aim of the project was to clarify the association between unemployment risk and decreased income at 4 years after the diagnosis of testicular cancer (TC). Participants and methodsA case control in a cohort study includes baseline measurement of people participating in the Israeli Central Bureau of Statistics 1995 National Census, and follow-up until 2011. Cancer incidence, employment status, and income level were ascertained through the Israel Cancer Registry and Tax Authority, respectively. A matched group was sampled from the population in the census. Binary logistic regression analyses were used to assess odds ratios (ORs) for study׳s outcomes, while controlling for age, ethnicity, education, and socioeconomic and employment status at 2 years before diagnosis. ResultsA total of 113 cases of TC and 468 persons in the matched group were included in the study after excluding persons who died during the study period. No association was found between TC and subsequent risk after the 4 years of unemployment (OR = 1.12, 95% CI: 0.65–1.95) or decreased income (OR = 1.41, 95% CI: 0.84–2.36). Predictors of subsequent unemployment were unemployment 2 years before diagnosis (OR = 6.91, 95% CI: 4.39–10.86) and increasing age (OR = 1.03 per year, 95% CI: 1.01–1.06). ConclusionTC survivorship is not associated with subsequent unemployment or decreased income at 4 years after diagnosis.

Prediagnostic self-assessed health and extent of social networks predict survival in older individuals with cancer: a population based cohort study.

To assess the association between social networks on survival after cancer diagnosis in a population-based sample of elderly Israelis (>60 yo) living in the community in 1985 and followed for up to 20 years. We conducted a historical prospective study, using baseline measurements from a 1985 survey of a representative sample of community-dwelling population. Five distinct social networks were defined using information regarding number and intensity of social contacts: traditional-family (reference category), friends and neighbors, narrow-family, diverse, and attenuated. Cancer was ascertained through the Israel Cancer Registry, and mortality through the Population Registry after 20 years of follow-up. The final study population included 676 participants diagnosed with cancer after 1985. Persons in the diverse network showed a lower risk of death (HR=0.74, 95% CI: 0.56-0.98) after adjusting for age, sex, smoking and self-assessed health. On the other hand, poor self-rated health at baseline (HR=1.39, 95% CI: 1.10-1.74 poor vs. all other categories of self-assessed health) was associated with increased risk of death. After excluding cancers amenable to early detection (breast, prostate, and colon) a borderline significant decreased risk of death following a diagnosis of cancer (HR=0.72, 95% CI: 0.52-1.01) was found. There is evidence of a significant protective association between diverse social networks present before a cancer diagnosis and survival after the onset of disease. Social support from a variety of sources may be an important element in improving cancer survival in older individuals.

Survival after cancer diagnosis among patients with higher income and education in Israel, a country with highly appreciated health service.

1598 Background: In recent years, the 5 year survival following cancer diagnosis is about two thirds. Among patients with various chronic diseases, improved survival is known to be associated with higher income and education. The aim of the current study is to assess the influence of income and education on survival following cancer diagnosis in Israel. Methods: Retrospective cohort study, using baseline measurement from the 1995 census conducted by the Central Bureau of Statistics in Israel. Cancer data were obtained from the Israel Cancer Registry. Cox proportional hazards ratios were calculated for mortality among cancer patients and adjusted for age, sex, religious, income and education years. The first model excluded cancers associated with early detection (breast, prostate, colorectal and cervix), and a second model excluded also lung cancer in order to control for smoking which is common in lower socioeconomic status. Results: A total of 3,712 cases of cancer and 1,252 deaths were reported during the study period. Higher income (HR=0.985 per 1000NIS, approximately 330$ in 1995's value, p=0.016) and education (HR=0.957 per year of education, p&lt;0.001) were associated with decreased risk of death after cancer diagnosis. Jews had better prognosis than non-Jews following cancer diagnosis (HR=0.62, p&lt;0.001), while males (HR=1.54, p&lt;0.001) and age (HR=1.036 per year, p&lt;0.001) had been associated with worse prognosis. The association between higher income and education was not changed in a model which excluded lung cancer. Conclusions: Higher income and education are associated with improved survival after cancer diagnosis. In the light of current study, further studies are needed to depict the variation in cancer incidence, stage at diagnosis and treatment disparities related to socioeconomic variables.

Statin and aspirin use and risk of VTEs in ovarian cancer patients.

5576 Background: Deep vein thrombosis and pulmonary embolism - venous thromboembolic events (VTEs) - are associated with significant morbidity and increased risk of mortality in cancer patients. Ovarian cancer patients are at a particularly increased risk for VTEs. Statins and aspirin have been shown to reduce the risk of VTEs in the general population in randomized trials. However, the effect of these medications on the incidence of VTEs in ovarian cancer patients has not been studied. Methods: Patients diagnosed with ovarian cancer between years 2000 and 2011 were identified through the Israeli Cancer Registry (ICR). Patients insured by Clalit Health Services, the largest HMO in Israel, were included. Data regarding medication use, chronic diseases and VTE diagnosis were extracted from the computerized database. Patients taking Warfarin or Low Molecular Weight Heparin for 3 months or longer were excluded. Statistical analysis was performed using SPSS (v 18). Use of medications was analyzed as a time dependent covariate in a Cox regression model. Results: Of 1,886 patients 179 (9.5%) had a VTE during a median follow up of 3.13 years. 95 patients (5%) had a VTE 2 years after diagnosis of ovarian cancer. In a multivariate analysis use of chemotherapy and stage 3 or 4 at presentation were associated with an increased risk for VTE's 2 years after diagnosis. Age was associated with a trend for increased risk. Statins were used by 43.2% of the patients, and 31.9% used aspirin. Aspirin use was associated with a reduced incidence of a VTE, which was borderline statistically significant (p=0.054). Statin use did not affect the incidence of VTE's in the group of ovarian carcinoma patients. Conclusions: Our results suggest that in patients with ovarian cancer aspirin use is a possible protector from deep vein thrombosis and pulmonary embolism. Prospective trials are warranted to assess the benefit of aspirin and statins for prevention of VTE's in the high risk population of ovarian cancer patients. [Table: see text]

Increased incidence of chronic lymphocytic leukaemia and lymphomas in patients with Merkel cell carcinoma – a population based study of 335 cases with neuroendocrine skin tumour

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 55·6years 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.

Radiation Therapy for Prostate Cancer Increases the Risk of Subsequent Rectal Cancer

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. 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. 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. 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.

3.17 Similar Rates of Invasive Fungal Disease in CLL and ‘High-Risk' Acute Myeloid Leukaemia/Allogeneic Transplant Patients

especially CLL /small lymphocytic lymphoma (SLL), and to study impact on overall survival (OS). Materials and methods: According to the Israel Cancer Registry, 503 cases of MCC were diagnosed in Israel during the period 1982-2009. Data were collected on age, sex, and ethnic origin, dates of diagnosis of MCC and other tumors, and dates and causes of death when applicable. The incidence of second neoplasms in MCC was compared with more than 4400 age-, ethnicityand period-matched controls diagnosed with primary neoplasms in the Jewish population. The age-specific standardized incidence ratio (SIR) was calculated with a 95% CI. Results: During the years 1989-2009, the incidence of MCC in Israel increased. Overall, 97% of cases were diagnosed in Jewish Israelis, while the remaining 3% included Arabs and non-Arab non-Jews. From this data, it is evident that MCC is more frequent in people with lighter skin, which is more common in Jews than in the Arab population and mostly encountered among ‘Ashkenazis’ or Jews migrating to Israel from the US or Europe. The median age at diagnosis was 73.3 years in the Jewish patients and 56 years in the Arab population. Second cancers were found in 104 patients, with 35 occurring before and 31 after the diagnosis of MCC was established. The SIR for non-hematologic malignancies did not show a higher proportion of second tumors among MCC patients. Thirty of the 104 second cancers (28.8%) were hematologic malignancies, and of these 23 were detected before and 7 after the diagnosis of MCC. The SIR for second hematologic malignancy was 3.39 for males (95% CI 1.55-5.23) and 3.05 for females (95% CI 1.06-5.04).The most frequent hematologic neoplasms encountered were CLL/SLL (46.6%) and nonHodgkin lymphoma (50%). Conclusions: There is an increased incidence of CLL/SLL in patients with MCC in Israel, especially among the Jewish Ashkenazi population. Recently, progress in the understanding of the pathogenesis of MCC has been made with the discovery of a link between a polyomavirus and this rare neuroendocrine tumor. The virus was termed Merkel cell polyomavirus, and its expression was recently analyzed in highly purified CLL cells with contradictory and controversial results. Further studies are needed to obtain a better understanding of the pathogenesis of MCC in CLL and the link between these 2 malignancies. Of these cases of MCC, 77% occurred after the diagnosis of CLL or lymphoma had already been made. This association should be considered when evaluating patients with B-cell lymphoproliferative disorders and a coexistent skin tumor.Figure 1

ENVIROMENTAL EXPOSURE TO CADMIUM IS ASSOCIATED WITH INCREASED RISK OF CANCER

Background and Aims: Association between environmental exposure to Cadmium and cancer incidence was reported by few studies with conflicting results. The aim of the current study was to evaluate the association between Cadmium exposure and cancer incidence in a cohort of people living in an industrial subdistrict of Israel, followed for 13 years. Methods: A historical prospective study, with cohort inception and baseline measurement of people participating in the Central Bureau of Statistics 1995 census, was designed. To asses Cadmium soil concentration possible contribution to cancer incidence, a geochemical survey was analyzed. Cadmium concentration in soil was analyzed in 1823 samples in Haifa and the West Galilee (total 162 km2), which houses major industrial facilities. An Arithmetic mean of Cadmium measurements in a census block (aCd) was calculated. Cancer incidence was ascertained through the Israel Cancer Registry and was calculated after adjusting for age, sex, origin and years of education. Results: 37,690 people were followed and 1759 developed cancer throughout the study's follow-up period. Of these 18,408 people live in areas with aCd above the limit of detection. Living in areas where aCd is detected was associated with increased cancer incidence (Hazard ratio (HR) 1.11 95% CI: 1.01-1.23, P=0.038). People age 41-65 living in areas where aCd is detected were found to have an increased cancer incidence (HR 1.21, 95% CI: 1.09-1.40, P =0.014). In this age group, people living in areas where aCd is 0.1-1.5 ppm show no difference in cancer incidence (HR 1.15, 95% CI: 0.96-1.36, P =0.118), where as in people living in areas where aCd is above 1.5 ppm an increase in cancer incidence is found (HR 1.27, 95% CI: 1.07-1.51, P =0.007). Conclusion: We report an increase of cancer incidence in Cadmium rich areas in a dose dependent manner among people age 41-65.

Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma

Data on the association between smoking and meningioma are inconsistent. The aim of this study was to assess the role of smoking in radiation- and non-radiation-related meningiomas. The study was designed as a 4-group case-control study, balanced for irradiation, including 160 irradiated meningioma case patients, 145 irradiated control subjects, 82 nonirradiated case patients, and 135 nonirradiated control subjects. The sources of these groups included a cohort of individuals who underwent radiotherapy (mean dose, 1.5 Gy to the brain) during childhood for treatment of tinea capitis, claims filed for radiation damage in the framework of a compensation law, and the Israel Cancer Registry. All tests of statistical significance were 2-sided. A statistically significantly elevated risk of meningioma was found among men who had ever smoked, compared with those who were never smokers (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.09-4.15), increasing with smoking pack-years from 1.67 to 2.69 for <10 to >20 pack-years, respectively. Among women, an interaction between radiation and smoking was observed, expressed by a significant protective effect for meningioma (OR, 0.32; 95% CI, 0.14-0.77), with a strong dose-response association (P < .01) in non-irradiated women and a nonsignificant increased risk of meningioma among those who were irradiated (OR, 1.23; 95% CI, 0.68-2.23). Variation in the association between smoking and meningioma may be explained by effects of distinct host factors, such as past exposure to ionizing radiation and/or hormonal factors.

The changing epidemiology of colorectal cancer and its relevance for adapting screening guidelines and methods

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<0.001 for both). However, the percentage for CRC patients aged between 50 and 74 years decreased but those who were aged more than 75 years increased (P<0.001 for both). Therefore, 45.3% of patients (39.1% aged ≥ 75 years) would not be electively screened. In addition, there was an increased trend (P<0.001) for right-sided (from cecum to and including the splenic flexure) CRC in patients both 50-74 and more than 75 years old. During 1999-2008, as compared with patients aged between 50 and 74 years, those below 50 years were less likely to be diagnosed with stage 1 or 2 CRC and more likely have stage 3 or 4 CRC (P<0.01 for all), whereas those aged more than 75 years were less likely to have stage 3 CRC (P<0.01). These results should influence CRC screening age guidelines, especially for 'healthy' individuals aged 75 years or more, and their need for noninvasive, but sensitive and specific pre-colonoscopy screening methodologies. In addition, the more advanced cancer stage in the patients aged below 50 years needs to make the treating physicians more aware of the fact that CRC can occur even at this age.

Risk factors for cancer among elderly: The Jerusalem longitudinal cohort study

Abstract 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.