Association between metabolic syndrome, diabetes mellitus and prostate cancer risk.

BACKGROUND: The worldwide incidence of diabetes mellitus is rapidly increasing. There is recent interest in the influence of glucose metabolism on oncogenesis. We investigated the role of diabetes mellitus and the metabolic syndrome (MS) on prostate cancer development. METHODS: This study consisted of 11 541 men with coronary heart disease screened to participate in a secondary cardiac prevention trial. MS was defined according to modified NCEP/ATP III criteria. Multivariable regression analysis accounting for competing risks was performed using a modified Cox proportional hazard model in order to assess the association between diabetes, the MS and the subsequent development of prostate cancer. RESULTS: At baseline, subjects were classified into one of the four groups: (1) 6119 (53%) with neither diabetic mellitus nor MS, (2) 3376 (29%) with the MS but without diabetes, (3) 560 (5%) with diabetes mellitus but without MS and (4) 1486 (13%) with both conditions. Median follow-up was 12.7 years (range 0-15.7 years). During follow-up, 459 new cases of prostate cancer were recorded. The age-adjusted hazard ratio (HR) for prostate cancer was reduced in diabetic patients compared with those without diabetes, 0.54 and 95% confidence interval of 0.40-0.73. No significant association was noted between the presence of MS and prostate cancer development. On multivariate analysis, diabetes mellitus continued to protect against the development of prostate cancer, this was more pronounced in the absence of MS (HR=0.43, P=0.01 for diabetes in the absence of MS; HR=0.64, P=0.08 in the presence of MS). CONCLUSIONS: The results of this study indicate an inverse association between type 2 diabetes mellitus and prostate cancer risk.

Severe caloric restriction in young women during World War II and subsequent breast cancer risk.

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.

High prevalence of malignant melanoma in Israeli patients with Parkinson's disease.

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.

The changing face of cancer in the elderly: only a demographic change?

The cancer burden of the elderly is high and has increased over time. One reason for this is increased longevity. Increasing age-specific rates of cancer in this age-group may also explain this phenomenon. Two age-groups were examined, older than 65 years and those younger than 65. The age-specific rates for all cancers combined among the Jewish population in Israel were identified via the Israel Cancer Registry during the years 1973-2002. Comparing the years 1973-1977 and 1998-2002, the age-specific rates for all cancers combined increased by about 35% in both age-groups. The most prominent increase was in prostate cancer in men (176% in the older group, p<0.01 and 368% in the younger group, p=0.01) followed by breast cancer in women (64% in the older group, p<0.01 and 50% in the younger group, p<0.01). In the years 1993-2002 a shift toward stabilization and even a decrease in incidence has been noted in some of the cancers, mainly in people aged 65 years and older. These data do not support the hypothesis that the overall change in the cancer burden in the aged could be explained by differences in the risk of developing cancer between these two age-groups.

High incidence of non-upper aerodigestive primary tumors in patients with esophageal cancer.

Earlier reports have described an association between esophageal cancer (EC) and high incidence of other primary tumors (OPTs) of the upper aerodigestive tract and breast cancer. We evaluated the incidence of non-upper aerodigestive OPTs among Israeli EC patients; 2328 EC patients were retrieved from the Israeli National Cancer Registry between 1980 and 2004. The relative risk of OPTs for EC patients was measured using standardized incidence ratio (SIR). Two cohorts, Israeli National Cancer Registry registered colorectal cancer (CRC) patients and the general Israeli population, were used for reference; 297 EC patients (12.7%) had OPTs, including breast (18.9%), CRC (16.2%), prostate (8.8%), and bladder (8.4%) cancers. Upper aerodigestive OPTs were less common. Most OPTs were identified before (74.4%) or simultaneously with (13.8%) EC diagnosis. The median time interval between OPTs diagnoses and EC development was 6.0 years. The incidence of OPTs was significantly higher among EC patients compared with CRC patients (SIR: 2.05, P < 0.01) or the general Israeli population (SIR: 3.90, 95% CI: 3.46-4.34, P < 0.01) regardless of gender or tumor histology. Patients with EC have high incidence of non-upper aerodigestive malignancies. Unlike previous reports, the distribution of OPTs in EC seems to represent the relative incidences of these cancers in the western populations.

Late fetal death in offspring and subsequent incidence of prostate cancer in fathers: the Jerusalem Perinatal Study cohort.

BACKGROUND: Little is known of the causes of prostate cancer and few previous studies have investigated men's reproductive histories in relation to this disease. We sought to determine whether risk of prostate cancer was altered in men who had fathered stillborn offspring. METHODS: We studied the incidence of prostate cancer (N = 252) in a cohort of 15,268 fathers followed for 28-41 years from the birth of a live offspring, whose wives participated in one of two separate surveys of outcomes of previous births. Proportional hazards models were used to estimate relative risks (RR) associated with previous stillbirths, controlling for changes in incidence over time, social and occupational factors. RESULTS: The 543 men with one or more stillborn offspring experienced an increased risk of prostate cancer (adjusted RR = 1.87, 95% confidence interval = 1.17-3.00, P = 0.0095), compared to men without stillbirths. With one reported stillbirth, the RR was 1.68 (0.99-2.84); with two or more, the RR was 3.29 (1.22-8.88). Results were consistent in men whose wives were interviewed in 1965-1968 and 1974-1976. In 100 fathers with no male offspring and at least one stillbirth the RR was 4.04 (1.87-8.71, P = 0.0004). CONCLUSIONS: These findings should be considered hypothesis-generating and require confirmation in other studies. They suggest that stillbirth and prostate cancer may have shared environmental causes; alternatively, genetic susceptibility to prostate cancer might increase the risk of a stillbirth in offspring.

Cancer risk among parents and siblings of patients with schizophrenia.

BACKGROUND: A 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. AIMS: To investigate the risk of cancer among the biological parents and full siblings of people receiving in-patient care for schizophrenia. METHOD: Linkage 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. RESULTS: A 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. CONCLUSIONS: The 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.

Malignancies following bilateral salpingo-oophorectomy (BSO).

AIMS: Prophylactic bilateral salpingo-oophorectomy (BSO) is an effective risk reducing measure in ovarian cancer susceptible women. Yet, a small subset of women develop primary peritoneal carcinomatosis (PPC) after BSO. The rates of PPC following non-risk reducing BSO have sparingly been reported. METHODS: Women who underwent BSO for non-cancer reasons from 1/1/1984 to 12/31/2000 were crossed with the list of cancer diagnoses reported to the Israel National Cancer Registry until 12/31/2001. RESULTS: Overall, 4128 women at a mean age of 58+/-12 years were analyzed. After a mean of 7.2+/-4 years following BSO, 147 women (3.6%) were diagnosed with cancer: breast cancer in 50 women 62+/-50 months after BSO, and one patient developed PPC, whereas the expected was 0.15 cases. The Standardized Incidence Ratio (SIR) of developing breast cancer was statistically significant lower than expected (SIR 0.71, 95% C.I. 0.44-0.78). CONCLUSION: The rate of post-oophorectomy PPC in average risk population is low, and BSO appears to lower the rate of breast cancer in average risk women.

A decreasing incidence of ovarian carcinoma in Israel.

The aim of the present study was to assess the incidence trend of invasive epithelial ovarian carcinoma in Israel. We assessed the incidence rate of invasive epithelial ovarian cancer in Israeli Jewish women during the 10-year period from 1993 to 2002 based on data obtained from the population-based Israel National Cancer Registry. There was a gradual significant decrease in the incidence of ovarian cancer from 9.64 in 1993 to 6.55 in 2002. The decrease in incidence was evident in all ethnic groups except those born in Asia and in all the age groups older than 35 years. The decrease in incidence of ovarian carcinoma is gratifying, but its reason remains obscure.

A comparison of population-based cancer incidence rates in Israel and Jordan.

Reliable information about comparative cancer incidence in the Middle East has been lacking. The Middle East Cancer Consortium (MECC) has formed a network of population-based registries with standardized basic data. Here the age-adjusted cancer incidences are compared for four populations: Israeli Jews, Israeli non-Jews, Jordanians and the US Surveillance Epidemiology and End Results (SEER) population, for the years 1996-1997 (Israel) and 1996-1998 (other populations). The all-sites rate of cancer is approximately twice as high in Israeli Jews and SEER, compared with Israeli non-Jews and Jordanians. Rates of lung cancer are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians. Childhood leukaemia rates in Jordan are higher than in Israeli Jews, but lower than SEER. Hodgkin lymphoma rates in Israeli non-Jews and Jordanians are similar to SEER, but non-Hodgkin lymphoma rates are lower than SEER. The previous suspicion of higher overall leukaemia and lymphoma rates in Jordan is thus not confirmed.

Long-term follow-up of patients with initially benign thyroid fine-needle aspirations.

Fine-needle aspiration (FNA) is currently the most reliable diagnostic means in the clinical work-up of thyroid nodules. However, most of the available data on the diagnostic reliability of thyroid FNA derives from biopsies done just before surgery or from short-term observations, whereas data on the long-term reliability of benign FNA results, is extremely limited. Over the 17-year period between 1979 and 1996, thyroid FNA performed on 849 patients in our endocrine clinic. An initially benign result was reported in 578 patients for a total of 631 nodules. Mean follow-up period was 8.1 +/- 4.4 years (+/-standard deviation [SD]; median, 6.9 years). In order to ensure the completeness of our follow-up data, we supplemented our own patients' data with data from the Israel Cancer Registry for documentation of thyroid malignancy. Sixty-six of the patients with an initially benign FNA diagnosis were rebiopsied during follow-up. Five patients (0.85%) of all those with an initial benign FNA diagnosis, were subsequently found to have thyroid malignancy diagnosed 6 months or more after the initial evaluation. Three of the newly diagnosed malignancies were follicular and two were papillary carcinomas. Three of the patients had elements of being at high-risk: previous head irradiation, previous thyroid surgery with an occult cancer, and a growing goiter, respectively. Only 1 of 35 patients who had more than one benign FNA results was subsequently diagnosed with thyroid malignancy (follicular carcinoma). These results indicate that the rate of subsequent thyroid malignancies in patients with an initial benign FNA diagnosis is low, and thus benign thyroid FNA results provide a high level of long-term assurance. Still, repeating FNA is warranted in patients with longstanding thyroid nodules, particularly if at increased risk for cancer, or if a goiter is found to have changed its morphological characteristics over time.

Ovulation induction and risk of endometrial cancer: a pilot study.

OBJECTIVE: To determine whether women with endometrial carcinoma are more likely to have been exposed to fertility drugs, in particular clomiphene, than healthy population controls. STUDY DESIGN: A nationwide case-control, pilot study. About 128 living women 35-64 years old, with a histologically confirmed diagnosis of endometrial carcinoma that was first diagnosed and reported to The Israel Cancer Registry between 1 January 1989 and 31 December 1992 were enrolled. The controls were 255 women from the same dialing areas selected by random digit dialing. A variety of demographic and clinical parameters were compared between cases and controls. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. RESULTS: About 7 women with endometrial carcinoma (5.5%) and 10 healthy controls (3.9%) reported that they had used any fertility drug (crude odds ratio (OR) 1.4; 95% confidence interval (CI) 0.47-4.2). Use of fertility drugs did not meet the criteria for entry into the logistic model. The following parameters were found to be independently associated with endometrial cancer controlling for age, European-American background OR=2.2, (95% CI 1.3-3.7, P=0.004); nulliparity OR=2.7 (95% CI 1.1-6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI> or =27 OR=2.3 (95% CI 1.4-3.9, P=0.001). The use of oral contraceptives and IUD were found to be protective, OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61, P=0.001 and 0.19-0.70, P=0.003, respectively). CONCLUSIONS: We found no evidence that the use of ovulation induction agents, including clomiphene citrate, are associated with a higher risk of endometrial carcinoma. The association between infertility drugs and endometrial carcinoma should be examined in other, larger studies.

Cancer registration in the Middle East.

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.

The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study.

BACKGROUND: The precise incidence of familial Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) in first-degree relatives is unknown. Through record linkage using two population-based sources, the authors estimated the risk of HD and NHL in family members of lymphoma probands. METHODS: The authors identified 8,037 first-degree relatives of 2,606 lymphoma cases (28.5% HD, 71.5% NHL) treated between 1970 and 1993 in 3 hospitals in Israel via the family file of the Population Registry. The authors linked this file with the Israel Cancer Registry, then calculated the standardized incidence ratio (SIR) by dividing the observed number of cases with the expected, adjusting for age, gender, calendar year, and continent of origin. RESULTS: The family file yielded incomplete ascertainment of relatives (for 771 probands, no relatives were identified). Twenty cases of lymphoma--6 HD and 14 NHL--were identified among relatives of lymphoma patients. The SIR for HD was 1.15 (95% confidence interval [CI]: 0.42-2.51) and for NHL 1.71 (95% CI: 0.93-2.87), considering the entire population of first-degree relatives. SIRs among siblings of lymphoma probands were 3.12 (95% CI: 1.01-7.29) for HD, 2.16 (95% CI: 0.45-6.31) for NHL, and 2.68 (95% CI: 1.15-5.27) for all lymphomas. There were 4 HD/HD, 1 NHL/NHL, and 3 NHL/HD sibling pairs. For HD/HD and NHL/NHL sibling pairs, the interval between lymphoma occurrence in proband and sibling was 1-4 years, whereas for HD/NHL pairs this ranged from 16 to 21 years. CONCLUSIONS: The risk of lymphoma among siblings of lymphoma probands was over 2.5-fold that of the general population and lower among other family members. The temporal proximity of HD/HD and NHL/NHL sibling pairs argues for environmental as well as genetic etiology. This method was hampered by incomplete data.

A worrying increase in the incidence of mesothelioma in Israel.

BACKGROUND: Exposure to asbestos is the main established cause of mesothelioma; the incidence of this tumor is thus often interpreted as an index of past exposure. Asbestos has been widely used in Israel in industry and building, exposing certain population groups to the risk of developing mesothelioma. OBJECTIVES: To analyze the incidence of mesothelioma in Israel during the years 1960-96, and to project its trend for the following years. METHODS: We conducted a population-based study of the incidence of mesothelioma reported to the Israel Cancer Registry during 1960-96. Time trends were analyzed from data on the annual import of asbestos to Israel, which may indicate the magnitude of past exposure. Based on these findings, trends in the incidence of mesothelioma in Israel were projected for the subsequent years. RESULTS: A total of 327 cases of mesothelioma were reported to the Israel Cancer Registry during the study period. The incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64 vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli-born males and males born in Europe and America showed the highest incidence (ASR 4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years younger than Jewish males born elsewhere. The incidence was twice as high among males than females and increased sevenfold from its nadir (1.17 per million/year) in 1978-80 to its peak (8.5 per million/year) in 1993-96. During a similar period the incidence among females increased from 0.33 to 2.56 per million/year. The incidence in both sexes does not appear to level off. The large wave of immigration from the former Soviet Union that began in 1989 only partly accounts for the increased incidence in 1993-96. The time trend in the incidence of mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked in the years 1976-78. CONCLUSIONS: The incidence of mesothelioma in Israel has increased sharply in recent years, unrelated to a wave of immigration from East Europe, and is predicted to continue to rise for another 10-15 years.

Childhood and adolescent ovarian malignant tumors in Israel. A nationwide study.

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.

Selected epidemiological time trends of vulvar carcinoma in Israel.

Recently, considerable demographic changes have occurred in Israel. The purpose of the present population-based nationwide epidemiological study of carcinoma of the vulva was to assess changes over time in incidence, relative frequency, age pattern and ethnic distribution. The study group included all 257 Jewish females with histologically confirmed neoplasms of the vulva diagnosed in Israel during the ten year period from 1985 to 1994. Data were obtained from the Israeli Cancer Registry and compared with data from a previous study covering a 13 year period (1961 to 1973). The relative frequency of carcinoma in situ (CIS) of the vulva increased significantly during the later period (from 5.4% to 12.8%), while that of invasive vulvar carcinoma declined significantly (from 80.6% to 69.6%). Regarding invasive vulvar carcinoma, a significant decrease in the age-adjusted standardized rates and in the mean annual incidence rate in the 70+ age group was found. The ethnic distribution pattern of invasive vulvar carcinoma did not change and remained similar to that of cervical carcinoma, namely a trend for higher incidence among women born in North Africa. The increased frequency of vulvar CIS is attributed mainly to a greater propensity to perform vulvar biopsies. The possibility of a consequent decline of vulvar carcinoma cannot be ruled out.

[Smoking and incidence of lung cancer, 1981-1995].

Smoking is the dominant risk factor for lung cancer. We compared trends in smoking with those of the incidence of lung cancer in Israel. The proportion of smokers has declined during the past 20 years; the decrease is greater in men than in women, and more marked in the elderly. Since 1980 the age-adjusted incidence of lung cancer in Jewish men has decreased slightly, but in women it has remained constant. Among Arab men there was an increase in age-adjusted incidence of lung cancer and since 1986 it has been higher than in Jewish men. The largest decrease in lung cancer incidence was among Jewish men aged 75 and over. This may be explained by data on the age of smoking cessation in the population. It was observed that the main decrease in smoking occurred among men over the age of 55 in the past 20 years, which correlates with the decline in lung cancer observed in the older age group. Lung cancer rates in Israel are lower than in other western countries despite the similar prevalence of smoking, for unknown reasons.