Posterior uveal malignant melanoma: temporal stability and ethnic variation in rates in Israel.

In a population-based study of posterior uveal malignant melanoma (755 incidence cases), the authors found a stabilized incidence in Israel from 1961-1996. Overall, Jewish immigrants to Israel had a relative rate (RR) of 2.2 [95% confidence interval [1.5-2.6] as compared to the reference population (Israeli-born Jews with Israel-born parents, i.e. third generation). Whereas individuals born in Eastern Europe or the Americas experienced the highest age adjusted incidence rates per million [for example; from 1972-1996, 8.3 for those from Poland, 8.2 from Romania, 6.4 from the former Union of Soviet Socialist Republics, 7.6 from the Americas], the lowest incidence rates were observed among immigrants from Algeria-Morocco-Tunisia (rate of 2.8), Iraq (1.7), Iran (3.2). Jews born in Israel exhibited incidence patterns similar to those individuals from the place of their parent's birth; high rates were observed among individuals born of American- or European-born parents (rate of 7.2), and low rates among offspring of parents who migrated from Africa or Asia (2.6). A low incidence was found among Israeli-born Arabs (2.6 in men, and 2.0 in women). The stable differences in incidence rates, according to populations of Jews, and the persistence of these variations within the descendants of these populations suggest that underlying susceptibility states are related to an individual's origin.

Use of sunscreen is linked with elevated naevi counts in Israeli school children and adolescents.

Epidemiological evidence indicates that a fair complexion and exposure to solar radiation in early years contribute to the proliferation of naevi and subsequent melanoma risk. To determine whether protection from sunlight is associated with lower naevi counts, we examined the prevalence and risk factors of naevi in a sample of Israeli school pupils. Whole body counts of naevi were recorded in 974 out of 1312 (74.2%) recruited pupils (7 and 12 year olds) from Ramat-Gan and Jerusalem. Host characteristics and habits of sun exposure were obtained using questionnaires. In each age group and geographic area, the mean whole body naevi counts, adjusted for confounders, were higher among males, pupils of European-American descent, and those susceptible to sunburn. The contributions to naevi risk of fair skin colour and frequent recreational sun exposure were higher among 7 year olds. Regular sunscreen use contributed to the naevi risk for both age strata in Ramat-Gan (at age 7, rate ratio [RR] = 1.7, 95% confidence interval [CI] = 1.3-2.2; at age 12, RR = 1.5, 95% CI = 1.1-2.1). Among the younger age group in Ramat-Gan, even seldom compared with no use of sunscreen was associated with higher naevi counts (RR= 1.5, 95% CI = 1.2-2.0). Similar patterns were noted with the pupils from Jerusalem. In conclusion, the elevated naevi count with increased sunscreen use indicates that sunscreens apparently do not modify the genetic predisposition to naevi proliferation. For better protection of children and adolescents, including those who use sunscreens, from the naevogenic effect of solar radiation, they should be encouraged to limit their exposure and wear protective clothing when in the sun.

Cancer incidence and survival following bereavement.

OBJECTIVES: This study investigated the effect of parental bereavement on cancer incidence and survival. METHODS: A cohort of 6284 Jewish Israelis who lost an adult son in the Yom Kippur War or in an accident between 1970 and 1977 was followed for 20 years. We compared the incidence of cancer in this cohort with that among nonbereaved members of the population by logistic regression analysis. The survival of bereaved parents with cancer was compared with that of matched controls with cancer. RESULTS: Increased incidence was found for lymphatic and hematopoietic malignancies among the parents of accident victims (odds ratio [OR] = 2.01; 95% confidence interval [CI] = 1.30, 3.11) and among war-bereaved parents (OR = 1.47; 95% CI = 1.13, 1.92), as well as for melanomas (OR = 4.62 [95% CI = 1.93, 11.06] and 1.71 [95% CI = 1.06, 2.76], respectively). Accident-bereaved parents also had an increased risk of respiratory cancer (OR = 1.50; 95% CI = 1.07, 2.11). The survival study showed that the risk of death was increased by bereavement if the cancer had been diagnosed before the loss, but not after. CONCLUSIONS: This study showed an effect of stress on the incidence of malignancies for selected sites and accelerated demise among parents bereaved following a diagnosis of cancer, but not among those bereaved before such a diagnosis.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus in healthy adults in Israel.

To determine if Kaposi's sarcoma-associated herpesvirus (KSHV) prevalence is correlated with the 9-fold difference in the incidence of classic Kaposi's sarcoma observed among Israeli Jewish populations, we conducted a cross-sectional KSHV seroprevalence survey in a population of 166 HIV-seronegative healthy subjects from the general population (26 women, 140 men). Eight individuals (4.8%) (all men) were seropositive for KSHV; differences between men and women were not statistically significant. If we consider the sensitivity and specificity of the assays, the corrected prevalence would be 6.1% (95% confidence interval 2.0-10.1). We noticed a non-statistically 5.5-fold difference between individuals above and below 40 years of age, but did not find an association with the incidence of classic KS among the Israeli Jewish sub-population, according to their origin. This suggests that KSHV is only necessary, albeit not sufficient, cause of classic Kaposi's sarcoma.

Classic kaposi sarcoma: epidemiology and risk factors.

BACKGROUND: Although Kaposi sarcoma (KS) initially was described over a century ago, its biology remains enigmatic and conflicting. Whereas the classic type occurs mainly in older men of Mediterranean or Eastern European backgrounds and is not linked to impairment of the host immune response, iatrogenic and human immunodeficiency virus (HIV)-associated KS are linked to such conditions. A recently discovered pathogen, KS-associated herpesvirus (KSHV) (also known as human herpesvirus 8 [HHV8]), is found in tissues from all four forms of KS (classic, iatrogenic, endemic [African], and HIV-associated). This universal detection of KSHV/HHV8 suggests a central role for the virus in the development of KS and a common etiology for all KS types. The epidemiology and risk factors of classic KS, along with the biology of KSHV/HHV8 and the prevalence of the virus among different populations, is presented. METHODS: The current review is based on multiple information sources, electronic health data in all languages from 1966 onward, and previously published scientific reports from the Americas, Europe, and Africa. RESULTS: Nearly 5000 cases of morphologically characterized classic KS have been reported in Europe, Mediterranean countries, and the Americas up to 1998. Geographic location, ethnicity, time interval, age, and gender heavily influence the incidence rate of classic KS. The rate of incidence of nonacquired immunodeficiency syndrome-associated KS correlates with the KSHV/HHV8 seroprevalence in the general population. CONCLUSIONS: Many contributory factors undoubtedly have etiologic and pathogenic significance in the development of classic KS; however, the interplay between these factors has complicated the understanding of the induction and development of the disease as well as the significance of each factor. As with other cell-transforming human DNA viruses, infection with KSHV/HHV8 alone is not sufficient for the development of KS and additional cofactors are required.

Malignant mesothelioma in Israel, 1961-1992.

The authors monitored time trends in the incidences and distributions of malignant mesotheliomas during 1961-92 in 223 Israeli persons, including 21 men from a cohort of 3,057 asbestos-cement workers (83,122 person-years). The annual incidence rates of malignant mesotheliomas in Jewish men ranged between 2.5 per million in 1961-82 and 4.6 per million in 1985-92. The male-to-female incidence ratio rose from 1.2 in the 1960s to 2.9 during 1985-92, as a result of increases in risk among Israeli-born males. Females accounted for 37.6% of all cases, after exclusion of the cohort of asbestos workers. Of the 223 cases, 202 (91%) had no indication of direct occupational exposure to asbestos. In Jewish females, the incidence of malignant mesotheliomas did not increase after 1961. The mean age at diagnosis in all cases was lowest in the Israeli-born (53.0 years). High levels of asbestos exposure in the 1970s and the relatively early age of onset of the disease indicate that exposure began at a younger age in Israel than in European countries. Asbestos manufacture and use peaked in Israel during the mid-1970s, so the maximum impact of these trends has yet to be seen.

Classic Kaposi's sarcoma as a first primary neoplasm.

Patients with a diagnosis of primary classic Kaposi's sarcoma (CKS) appear to be at a higher risk of multiple neoplasms. We analyzed a nation-wide series of 1,016 patients with a primary CKS occurring between 1961 and 1992 in the Jewish Israeli population to evaluate the risk of secondary neoplasms. The primary CKS and subsequent neoplasms were identified from the Israel Cancer Registry. All HIV-seropositive Kaposi's sarcoma cases were excluded. The expected number of second primary neoplasms was calculated after stratifying by age, origin and gender. Of the CKS patients, 61 developed a second neoplasm by the end of the study, similar to the expected number of 60.33 [standardized incidence ratio (SIR) of 1.01]. However, there was an excess of non-Hodgkin's lymphoma (NHL) (SIR = 3.94) and cutaneous malignant melanoma (SIR = 5.81), balanced by a deficit of lung cancers (none observed, 7 expected). We found high risk for migrants from Eastern Europe when compared with other migrants for both solid tumors [rate ratio (RR) = 3.01] and NHL (RR = 4.10). Patients with a diagnosis of primary CKS do not have an overall increased risk of new neoplasms later in life. However, an increased risk of NHL implies the presence of common risk factors for both NHL and CKS.

Classic Kaposi's sarcoma as a second primary neoplasm.

Although the incidence of classic Kaposi's sarcoma (CKS) has been investigated, its occurrence following a primary neoplasm and its association with this first neoplasm need to be determined. We analyzed a series of 124 patients with a secondary CKS (8.4% of a total of 1485 incident cases) which occurred between 1961 and 1992 in the Jewish Israeli population. Data on first neoplasms and subsequent Kaposi's sarcoma were retrieved from the Israel Cancer Registry. Acquired-immune-deficiency-syndrome-related Kaposi's sarcomas were excluded from the case series. Four controls were randomly selected for each CKS case among all Cancer Registry cases free from a second neoplasm at the time of diagnosis of the CKS in the case, and matched on gender, year of birth and year of diagnosis of the first neoplasm. The average time lapse between first neoplasm and secondary CKS was 4.5 years, being shorter for prostate cancer and for hematopoietic malignancies. As compared with Israel-born Jews, the risk of a subsequent CKS was significantly increased in immigrants [odds ratio (OR) 3.0]; this risk was particularly high in immigrants from the former Soviet Union (OR 9.4) and Poland (OR 7.0). There was no clear trend with age at immigration; however, low age at immigration and a short length of stay in Israel endowed a higher risk of developing a secondary CKS, markedly among patients suffering from solid tumors as the first primary. There was an excess of secondary CKS following a non-Hodgkin's lymphoma (OR 5.3), a Hodgkin's lymphoma (OR 7.5), a leukemia (OR 5.3) or a breast cancer (OR 2.2). Cancer patients with a first primary in the lung, colon, stomach, larynx, liver, pancreas or kidney showed secondary CKS less frequently. Despite the lack of control of therapy for the first neoplasm, development of secondary CKS seems to be mediated by mechanisms similar to those for hematopoietic neoplasms and selected nonhematopoietic neoplasms, such as breast cancer. The trend toward increased risk after a short time lapse and the difference in risk among immigrants indicate that genetic susceptibility is part of the complex interplay between cellular proliferation and control systems.

Cancer in ex-asbestos cement workers in Israel, 1953-1992.

A cohort of 3,057 male workers employed in an asbestos-cement plant using 90% chrysotile-10% crocidolite, located in Northern Israel, was followed from 1953-1992 for incidence and mortality from cancer. In the years 1978-1992, the cohort had an elevated risk for all malignant neoplasms combined (n = 153, SIR = 117, ns), lung cancer (n = 28, SIR = 135, ns), mesothelioma (n = 21; SIR > 5000, p < .0001), unspecified pleural cancer (n = 5; SIR = 278, P < .0001), and liver cancer (n = 7, SIR 290, ns). Risks for colo-rectal (n = 19; SIR = 79, ns), bladder (n = 12, SIR 69) and renal cancers (n = 5, SIR 104) were less than expected. Risk for mesothelioma showed a sharp risk gradient with duration of exposure, increasing from 1 per 625 for those employed less than 2 years to 1 per 4.5 workers employed over 30 years. The ratio of mesothelioma to excess lung cancer cases was 2.9 to 1, or 3.6 to 1, if pleural cases of unspecified origin were included; the pleura to peritoneum ratio of verified mesothelioma cases was 20 to 1. This atypically high ratio of mesothelioma to excess lung cancer cases is suggested to be the combined result of high past asbestos exposures in the workers and their low prior risk for lung cancer, and possibly, relatively early smoking cessation in relation to asbestos exposure.

The contribution of multiple data sources to a clinical audit of lymphoma in a teaching hospital.

OBJECTIVE: To assess the independent contribution of data sources used for case ascertainment in a clinical audit of the outcome of lymphoma patients in our institution. DESIGN: In the absence of a unified register of lymphoma patients diagnosed and/or treated in our institution, we used an elective approach to case ascertainment. Sources included two internal databases (computerized discharge data for hospitalizations and outpatient oncology database) and one external (Israel Cancer Registry) database. Histologic diagnosis was confirmed by search of on-line pathology files or discharge summaries. Demographic, histologic and survival characteristics were compared among patients identified through each data source. Survival was assessed via record linkage with the Population Registry. SETTING: A tertiary care university teaching hospital. STUDY PARTICIPANTS: Seven hundred and twelve patients with lymphoma diagnosed between 1987 and 1992. RESULTS: All three sources contributed independently to the total, with the majority (583 or 82%) via hospitalizations. Overlap among the sources was minimal with only 73 (10.3%) of the patients being common to all three sources. Differences (P < 0.05) in the age distribution, country of birth and population groups (defined by religion) as well as histologic diagnoses among the sources were noted. In addition, survival of those ascertained via the outpatient database was higher than those ascertained from other sources (P=0.02 for Hodgkin's disease) even after controlling for age. CONCLUSIONS: The use of multiple data sources for case ascertainment in clinical audit is justified when no patient register exists. The results indicate that use of a single internal data source would have resulted both in an underestimate of the scope of lymphoma in our institution and significant bias in terms of patient characteristics and outcome.

Introduction to the post-Human Genome Project era, a target for interactions between polygenic and/or multiphenotypical components in cancer control in South America.

Epidemiological studies have suggested that the propensity to develop malignancy involves a complex mix of genetic and environmental determinants, however both older and innovative techniques display unresolved fundamental questions regarding etiology. Current barriers to achieving the potential benefit from this understanding are: 1) incomplete background on the various environmental and genetic factors involved in the carcinogenesis mechanism; 2) difficulties in accurately differentiating specific molecular subtypes and measuring the effective cellular exposure dose; and 3) difficulties in determining the multifactorial interaction between genetic and environmental factors. To extrapolate Human Genome Project research findings to the Post-Human Genome Project era, South America provides a large population and large-pedigree families, thus including genetically heterogeneous and less heterogeneous groups. An initial strategy might be to trace high risk populations and the respective exposures to which they are susceptible, such as: 1) migration, identifying rural migrant populations; 2) inherent susceptibility, studying "long term homogeneous populations" or large families living in similar rural environments; and 3) dissection of gene-environmental interaction

Classic Kaposi's sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study.

BACKGROUND: The incidence of classic Kaposi's sarcoma (CKS) has been reported to be high in Jewish populations, mostly born in Eastern Europe. OBJECTIVE: To describe the incidence on CKS in Israeli Jews and to determine differences in incidence according to their geography origin. DESIGN: We analysed data on 1098 incident CKS cases with known country of origin occurring between 1961 and 1989 in the Jewish Israeli population. Reporting systems were the Israel Cancer Registry, the medical documentation of all-Kaposi's sarcoma cases and the registry of HIV-seropositive patients. Patients who were seropositive for HIV were excluded from the study population. Population figures for groups of migrants and natives were derived from census surveys (1961, 1972, 1983) and inter-census estimates based on the population registry. RESULTS: The overall age-standardized rate of CKS was 16.9 per million in men and 6.3 per million in women. The ratio between genders remained stable during the study period. In both genders, there was a steep increase in CKS incidence between the late 1960s (age-standardized rates per million: 8.0 in men and 2.2 in women) and the early 1970s (17.9 in men and 6.7 in women). No further increase was present after 1971. Overall, immigrants experienced a relative risk (RR) of 1.17 [95% confidence interval (CI) 0.90-1.521 compared with Jews born in Israel. Immigrants from Morocco, Algeria and Tunisia had the highest incidence (RR 2.01; 95% CI 1.52-2.65) compared with Jews born in Israel, followed by those born in Iraq (RR 1.74; CI 95% 1.27-2.37). The lowest incidence was experienced by immigrants from Iran (RR 0.37; CI 95% 0.18-0.77) and from Central European countries (RR 0.45; CI 95% 0.30-0.66). Immigrants from other countries in Asia, Africa, the Americas and Europe had similar rates as Jews born in Israel. CONCLUSIONS: Israeli Jews present one of the highest incidences of CKS reported from developed countries. The incidence varies according to geographical origin. Countries surrounding the Mediterranean sea represent the area of highest CKS incidence.

Classic Kaposi's sarcoma in Arabs living in Israel, 1970-1993: a population-based incidence study.

The incidence of classic Kaposi's sarcoma (CKS) has been reported to be high in Jewish populations living in Israel and in immigrants originating from the Mediterranean basin. No population-based reports are available on the incidence of CKS in Israeli Arabs. We analyzed the incidence of CKS cases occurring between 1970 and 1993 among Arabs living in Israel. Reporting systems were the Israel Cancer Registry, the medical documentation of all-Kaposi's sarcoma cases and the registry of human immunodeficiency virus-seropositive patients. Population figures were derived for census surveys (1972 and 1983) and inter-census data based on annual updating of demographic characteristics. Age-standardized incidence rates (ASR) were 6.87 per million in men and 2.18 per million in women. The ASR did not increase between 1970 and 1993 in either men or women. The age-adjusted male to female ratio was 2.0 below 50 years of age and 3.5 above it. The observation of a stable and relatively high incidence of CKS in Israel-born Arabs, comparable to other populations living in the Mediterranean basin, suggests that risk is related to geographical origin. CKS incidence, however, is lower than that in Israel-born Jews.

Cancer incidence patterns (1972-91) among migrants from the Soviet Union to Israel.

A proportional cancer incidence analysis is reported, based on 6,563 cases of cancer diagnosed in Israel between 1972 and 1991 among migrants from the former Soviet Union who arrived in Israel between 1972 and 1986. For digestive system cancers, there is evidence of a marked reduction in the risk of stomach cancer among the migrants with time since migration, and an increase in the proportion of colon cancer, although little change in cancer of the rectum. For most of the smoking-related cancers, there is little evidence of any meaningful change in proportions with time since immigration. For multiple myeloma, proportions decreased substantially in both men and women over the 20-year period. Among women, there is a small, statistically significant increase in breast cancer, and a marked decrease in cancer of the cervix. Among younger immigrants, the proportion of malignant melanoma has increased substantially since migration. A number of the changes in cancer patterns are consistent with various etiologic hypotheses including those based on possible dietary and other lifestyle changes among the migrants.

Cutaneous lymphoma in Israel, 1985-1993: a population-based incidence study.

The incidence rate of cutaneous lymphomas (CL) [including mycosis fungoides (MF) and non-mycosis fungoides (non-MF)] for the period 1985-93 in Israel was determined using data from the population-based Cancer Registry supplemented by a field survey that covered approximately 80% of lymphoma cases. After the field survey, corrected rates were 49% and 24% higher for MF and non-MF respectively (37% for CL overall). The age-adjusted incidence rates per 100,000 were 1.18 and 0.63 for Jewish men and women respectively. MF rates (0.77 in men and 0.35 in women) were higher than non-MF (0.41 and 0.28 respectively). Rates of CL were significantly lower in non-Jews. There were no significant differences in incidence among Jewish ethnic subgroups. However, the lack of variability in the incidence of these neoplasms among subpopulations is in contrast with findings for cutaneous malignant melanoma; the observed high rates of CL could, nonetheless, be consistent with the sunlight exposure hypothesis, operating perhaps through a different mechanism.

The incidence of borderline ovarian tumors in Israel: a population-based study.

BACKGROUND: In hospital-based studies, one-eighth of ovarian cancers have been considered borderline ovarian tumors (BOTs). Population-based data regarding the incidence of BOTs are lacking in the international literature. The authors' objectives were to measure the incidence of BOT in Israel and compare rates among ethnic groups (based on ethnic group and country of birth) for the years 1985-1993. METHODS: The authors analyzed data reported to a nationwide cancer registry. Population estimates by subpopulation were derived from census and intercensus estimates, which were based on an updated population registry. RESULTS: The age-adjusted standard rate (ASR) for the entire population was 10.6 per million (95% confidence interval [CI], 9.2-12.0) for the period 1985-1993. Significant differences in ASR were observed among ethnic subgroups, with the lowest incidence among non-Jews (ASR, 5.0 per million; 95% CI, 0.7-9.3) and the highest among new immigrants from the former Soviet Union (FSU) who had been arriving since 1989 (ASR, 22.7 per million; 95% CI: 14.2-31.3). Between the periods 1985-1989 and 1990-1993, the ASR for Jews nearly doubled (rate ratio, 1.86; 95% CI, 1.1-2.5). This near-doubling was influenced, but not wholly accounted for, by the immigration from FSU and was observed in all ethnic subgroups. CONCLUSIONS: The variations in the incidence rates of BOT among ethnic groups may be related to differences in fertility patterns, use of fertility drugs, and genetic predisposition. The pattern of near-doubling in rates may reflect biases caused by increased detection or shifts in the classification of ovarian tumors; if they are real, a biologic explanation is needed.

Clustering of leukaemia cases in a city in Israel.

A temporal cluster of cases may result from exposure to a new carcinogen, but it may also occur under stable conditions or as result of another factor, such as changes in medical practice. In this study, we used several complementary methods to detect a cluster and to conduct an initial investigation regarding its cause. The analyses included three stages, and were based on the time interval between consecutive diagnoses. First, we applied the sets monitoring technique to detect clustering. Following the detection (alarm), a confirmatory analysis was conducted in order to confirm or refute it as a true alarm. We applied this analysis to the first five cases diagnosed subsequent to the alarm. With a graphical display of the temporal pattern of the diagnoses, we considered the possible causes leading to the cluster. The data included registered diagnoses of leukaemia cases made from 1960 to 1990 among residents of Ashkelon, Israel. Clustering was detected for acute lymphatic leukaemia and for chronic myeloid leukaemia. We found that the temporal patterns of the diagnoses consistent with the possibility that these two clusters are due to exposure to a common local carcinogen. We cannot however, rule out the possibility that these clusters are due to unknown factors.

Prevalence of melanocytic nevi and freckles in young Israeli males. Correlation with melanoma incidence in Jewish migrants: demographic and host factors.

The role of host and environmental factors in the pathogenesis of multiple melanocytic nevi, atypical nevi, and freckles was studied in 1989 in a random sample of 3,040 Israeli males aged 17 years. Multiple melanocytic nevi were significantly associated with family history of melanoma or multiple melanocytic nevi (odds ratio (OR) = 15.0), fair or lightly pigmented skin color (OR = 2.7 and 2.3, respectively), and affiliation to the high or heterogenous melanoma risk group, determined by the incidence rates of melanoma in Jewish migrants from corresponding origin (OR = 3.1 and 2.1, respectively). An environment-related effect may account for the increased multiple melanocytic nevi risk among second- (OR = 8.2) compared with first-generation, native-born recruits (OR = 3.0) from the high melanoma risk group whose families had been living in Israel the longest. Atypical nevi were associated with fair (OR = 6.1) and lightly pigmented (OR = 3.5) skin color, high and moderate sunburn susceptibility (OR = 4.7 and 2.5, respectively), and family history of melanoma or multiple melanocytic nevi (OR = 4.7). Freckles were significantly associated with sun-sensitive phenotype, family history of melanoma or multiple melanocytic nevi (OR = 1.5). Conservative (OR = 1.9) or nonreligious status (OR = 1.9), and high (OR = 2.4) or heterogenous melanoma risk groups (OR = 1.8). These findings indicate that environmental factors may modify the occurrence of multiple melanocytic nevi and freckles in genetically susceptible ethnic groups.