Irena Liphshitz

Trends in colorectal cancer incidence and mortality in the Israeli Jewish ethnic populations.

Background: Ashkenazi Jews, as compared to non-European Jews and non-Jews, are at increased risk for colorectal cancer (CRC), this is attributed to genetic susceptibility and/or lifestyle. Aims: To follow Israeli long-term trends in CRC incidence and mortality and their associations with ethnicity. Methods: All Israeli CRC data accumulated 1970–2001 was used, age standardized rates (adjusted to world standard population) was computed by cancer site, US Surveillance, Epidemiology and End Results Program (SEER) Stage and ethnic group (continent of birth: Europe–America, Asia, Africa, Israel). Results: From 1970, CRC incidence increased 190% in males and 140% in females; mainly colon cancer (270% and 185% respectively) (P < 0.01), while rectal cancer incidence decreased and is now stable. Stage 3 CRC increased while stage 4 decreased significantly (P < 0.01 for both). In 2001, CRC incidence per 100,000 in European–American-born males was 48.3, Asian and African born 35.5 and Israeli born 32.7 (relative risk (RR) 1.36, P=0.03), while European–American female rates were 35 and all the others 26 (RR 1.35, P < 0.01). Overall survival increased 9% over 30 years (P 0.01), 5 years survival since 1988–1996 for European–American born was 43.1%, Asian 46.7%, African 47.5% and Israeli 55.8%. Stage-2 CRC 5 years survivals for 1970–1996 (most had no post surgical treatment) for European–American born were 41.7%, Asian and African 44.8% and Israeli 53.4% (P < 0.05). Stage-3 CRC survivals (most received adjuvant therapy in addition to surgery) for European–American born was 38.8%, Asian and African 43.3% and Israeli 45.1% (P < 0.01). Conclusions: Colon cancer has increased in Israel, mainly in males and European–American born. Israeli-born Jews (of 20 to 60% mixed ethnicity and lifestyle habits) have the lowest incidence and best survival data for stages-2 and -3 CRC. There is evidence of ethnic survival advantage and possibly in response to adjuvant oncological therapy.

Measured Body Mass Index in Adolescence and the Incidence of Colorectal Cancer in a Cohort of 1.1 Million Males

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

Changes in Brain Glioma Incidence and Laterality Correlates with Use of Mobile Phones - a Nationwide Population Based Study in Israel

INTRODUCTION Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumors laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. MATERIALS AND METHODS All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups--low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals. RESULTS A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03). CONCLUSIONS We found a statistically significant decrease in LGGs over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

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 55·6 years for the Arab population. Other associated malignancies were encountered in 92 patients (27·4%) with MCC (90 Jews, two Arabs). Of the Jewish cases, 66 presented with an associated malignancy before, and 24 after, the diagnosis of MCC. Solid tumours were not significantly increased among patients with MCC. Thirty‐one of these associated cancers (34·4%) were haemato‐oncological malignancies, 24 were detected before and seven after the diagnosis of MCC. The standardized incidence ratio (SIR) for haematological malignancy was 3·67 for males and 3·62 for females, and the most frequent haemato‐oncological neoplasias recorded were chronic lymphocytic leukaemia (45%) and lymphomas (29%). Although MCC is rare, clinicians should be aware of the possible association with B‐cell lymphoproliferative disorders when evaluating patients with neuroendocrine skin tumours.

The 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 precolonoscopy 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.

The changing incidence and sites of colorectal cancer in the Israeli Arab population and their clinical implications.

Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly proximal cancer, but increasing CRC is now noted. We examined this trend and CRC site and compared them to the total Jewish population and to the low‐risk Jews of Asian‐African origin. Israel Cancer Registry CRC data, 1982–2002, for Arabs and Jews was computed by gender, age and site: rectal cancer included recto‐sigmoid junction; “right‐sided” CRC included the proximal colon up to and also the splenic flexure. During 1982–2002, Arab CRC trends increased significantly in both sexes due to left‐sided CRC (women, p = 0.01; men, p = 0.02) and rectal cancers (p = 0.05). Left‐sided CRC increased significantly in both men and women aged ≥ 65 years (p = 0.02). Comparing 1982–1984 to 2000–2002, the proportion of right‐sided CRC decreased in both genders (p < 0.01) from 39.4 to 27.1% of male CRC, and from 44.8 to 31.3% in females. In general, this pattern of increasing rectal and left‐sided CRC had been seen over a decade earlier in Jews of Asian‐African origin and then their trend reversed during the last decade. In conclusion, there is a recent trend for left‐sided CRC in Israeli Arabs, probably related to their changing life style. These results should influence their cancer preventive lifestyle recommendations, and CRC screening and diagnostic methodologies used.

Breast cancer trends in Israeli Jewish and Arab women, 1996-2007.

Breast cancer is the most common malignancy in Israeli Jewish and Arab women. The main objective of this study was to reexamine the trends in breast cancer incidence, mortality, and survival in Israel in 1996 through 2007, as well as the use of mammography. Data were obtained from the Israel National Cancer Registry, the Central Bureau of Statistics, and National Health Surveys. Incidence and mortality rates per 100 000 are age adjusted to the world standard population. Time trends are presented using the joinpoint regression analysis. The relative survival was calculated for the diagnosis years 1996–2003. Data on mammography performance were obtained from the Knowledge, Attitudes and Practices surveys carried out in 2002–2008. From 1996 through 2007, the incidence of in-situ breast cancer increased in both subpopulations whereas the incidence of invasive breast cancer decreased by 3% for Jewish women and increased by 98% for Arab women (P value for ‘between-populations’ differences <0.001). Reports on having had a mammogram in the last 2 years increased by 16% in Jewish women and by 17% in Arab women in 2002 through 2008 (P=0.880). Breast cancer mortality rates decreased significantly from 24.7 in 1996 to 19.0 in 2007 in Jewish women, but remained stable in Arab women (P=0.041). The 5-year relative survival increased in both subpopulations (P=0.420). The incidence of breast cancer has been stable in Jewish women, but had been increasing rapidly in Arab women throughout 1996–2007. The differences indicate an epidemiologic transition in the Arab minority in Israel. Efforts should focus not only on secondary but also on primary prevention strategies.

Follow-up of patients undergoing both semiquantitated immunochemical fecal occult blood and colonoscopy examinations

The semiquantitated immunochemical fecal occult blood test (I-FOBT) used for colorectal cancer (CRC) screening has had its long-term performance characteristics determined by clinical follow-up or sometimes by colonoscopy as the ‘gold standard’. We reanalyzed a file of total colonoscopy patients who also prepared three I-FOBTs, processed by the OC-MICRO instrument, using at least 50 ng Hb/ml buffer threshold to determine a positive test. The performance of both tests was evaluated by the National Cancer Registry follow-up to identify new CRCs and by determining the effects of the number of tests prepared and their thresholds for analysis, sex, and age on results. A total of 1630 patients, mean age 62.7 years, SD 11.9, 50.1% men, having undergone both tests were followed up for a mean of 51.5 months, SD 13.4; 25 CRC patients were registered. At 36 months, I-FOBT sensitivity for CRC was 95.8% (95% confidence interval 87.8, 104), as was initial colonoscopy; within 48 months, it was 92% (95% confidence interval 81.4, 103) and 96%, respectively. I-FOBT identified 70 of the 122 (57.2%) colonoscopy-detected advanced adenoma patients. CRC and advanced adenomatous polyps were more common in men (P<0.01), whose risk increased at 51–73 years (odds ratio 4.639, P=0.056), but not among women (odds ratio 1.952). It then increased significantly (P<0.01) for both sexes aged at least 74 years. I-FOBTs identified most CRCs diagnosed within 36 months of follow-up with sensitivity similar to that of initial colonoscopy, with neither test identifying every CRC patient. Sex and age influence results and need consideration when planning population screening.

Familial Mediterranean Fever and Incidence of Cancer

Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested as recurrent serosal inflammation. An association between FMF and malignancy has not been evaluated. The aim of this study was to estimate cancer risk in a large cohort of FMF patients from a single institution.

Risk for colorectal cancer in elderly persons and possible methodologies for their screening

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