Israel Medical Association Journal

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Colonoscopy is the gold standard procedure for screening for colorectal cancer and surveillance after polypectomy or colorectal cancer surgery, for diagnosis in symptomatic patients and patients with fecal occult blood, and for screening in the high risk population. The adherence of referring physicians to the accepted recommendations can prevent long waiting lists for colonoscopy and save lives, costs and resources.

Objectives: To evaluate the knowledge of primary care physicians and gastroenterologists in Israel about current guidelines for colonoscopy screening and surveillance.

Methods: A 10-item questionnaire on proper follow-up colonoscopy for surveillance after polypectomy and screening for colorectal cancer in various clinical and epidemiological situations was administered to 100 expert gastroenterologists and 100 primary care physicians at a professional meeting. Answers were evaluated for each group of physicians and compared using the chi-square test.

Results: The compliance rate was 45% for the gastroenterologists and 80% for the primary care physicians. The rate of correct answers to the specific items ranged from 18.7% to 93.75% for the gastroenterologists and from 6.2% to 58.5% for the primary care physicians (P < 0.001 for almost every item).

Conclusions: The knowledge of physicians regarding the screening and surveillance of colorectal cancer needs to be improved.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Multiple primary malignancies are increasingly being detected among cancer patients. Objectives: To investigate the co-occurrence of primary bladder cancer and primary lung cancer, two established smoking-related neoplasms characteristically associated with increased risk of secondary cancers.

Methods: A retrospective search of the patient registry in our institution identified 25 patients (23 men and two women) who were diagnosed with both bladder cancer and lung cancer during the period 1990–2005. Medical records were reviewed and clinical and pathological data were extracted.

Results: In 21 patients (84%) bladder cancer was the first primary tumor and in 4 (16%) the second primary tumor. More than 90% of the patients had a history of smoking. Mean smoking exposure was 62.1 pack years (range 30–120). All bladder cancers were transitional cell carcinomas with the majority being superficial at presentation. Most lung cancers were of the non-small cell type. Second primary lung cancers were significantly more advanced at diagnosis. Overall, mean follow-up was 105.8 months (range 6–288). Seven patients (28%) were alive at the time of evaluation; 68% died of lung cancer, while none died of bladder cancer.

Conclusions: Second primary lung cancer may occur in patients with bladder carcinoma and vice versa. In view of the relatively frequent involvement of the genitourinary tract as a site of multiple primary tumors, urologists may have a key role in the detection of second primary tumors arising in the genitourinary tract, or second primary tumors that occur in patients with primary genitourinary tract malignancies.
 

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.

Background: The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children, who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer.

Objective: To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel.

Methods: We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel.

Results: We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999–2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime.

Conclusions: Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool.
 

Background: Type 2 diabetes, an extreme state of glucose intolerance, has been found to be associated with cancer mortality; less is known about impaired glucose tolerance and cancer incidence.

Objectives: To examine the association between fasting and post-load plasma glucose and insulin, and the 20 year incidence of cancer.

Methods: We followed a sample of the Jewish Israeli population (n=2780), free of cancer at baseline,

from 1977-1980 to 1999 for cancer incidence and mortality. Baseline fasting and 1 and 2 hour post-load plasma glucose levels were recorded, as was insulin in 1797 of them.

Results: During 20 years, 329 individuals (11.8%) developed cancer. Cancer incidence for all sites differed between men and women (13.0% and 10.7%, P = 0.03), and among different glucose tolerance status groups (P = 0.01). Cancer incidence hazard ratio, by glucose status adjusted for gender, age, ethnicity, smoking and body mass index, was 1.24 (95%CI 0.96–1.62, P = 0.10) for impaired fasting glucose or impaired glucose tolerance, and 1.32 (95%CI 0.96–1.81, P = 0.09) for type 2 diabetes mellitus, compared to those who were normoglycemic at baseline. Fasting insulin and cancer incidence were not associated.

Conclusions: An increased long-term cancer risk for individuals with impaired fasting glucose or glucose tolerance, or diabetes, is suggested. Even this modest association could have substantial public health consequences.
 

Background: Mucositis and dermatitis are frequently encountered in patients treated with radiochemotherapy. Dead Sea products that contain minerals and different substances have proved effective in treating various skin diseases.

Objectives: To evaluate the effectiveness of Dead Sea products in reducing acute radiochemotherapy‑induced side effects in patients with head and neck cancer.

Methods: In this phase 2 study we compared the outcomes in 24 treated patients and 30 conventionally treated patients matched for age, tumor site, and type of treatment. The Dead Sea products comprised a mouthwash solution (Lenom®) and a skin cream (Solaris®) used three times daily for 1 week before, during, and up to 2 weeks after completion of radiotherapy. Mucositis and dermatitis were evaluated using common toxicity criteria.

Results: Thirteen treated patients (54%) had grade 1-2 and none had 3-4 mucositis, while 17 controls (57%) had grade 1-2 and 4 (13%) had grade 3-4 mucositis. Thirteen treated patients (54%) had grade 1-2 dermatitis; there was no instance of grade 3-4 dermatitis, while 11 patients in the control group (37%) had grade 1-2 and 5 (17%) had grade 3-4 dermatitis. More patients in the control arm needed a break than the patients in the treatment arm (P = 0.034[T1]).

Conclusions: The two Dead Sea products tested decreased skin and mucosal toxicity in head and neck cancer patients receiving radiochemotherapy.
 

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.