Baruch Modan

The INTERPHONE study: design, epidemiological methods, and description of the study population

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case–control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case–control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

Long-Term Follow-up for Brain Tumor Development after Childhood Exposure to Ionizing Radiation for Tinea Capitis

Abstract Sadetzki, S., Chetrit, A., Freedman, L., Stovall, M., Modan, B. and Novikov, I. Long-Term Follow-up for Brain Tumor Development after Childhood Exposure to Ionizing Radiation for Tinea Capitis. Radiat. Res. 163, 424–432 (2005). Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43–9.12 and 0.73–4.69) and an EAR/Gy per 104 PY of 0.48 and 0.31 (95% CI = 0.28–0.73 and 0.12–0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.

Psychological and hormonal changes in the course of in vitro fertilization

This study was designed to investigate concurrently the psychological and hormonal changes at three critical points during in vitro fertilization (IVF) treatment. One hundred thirteen couples suffering from mechanical and unexplained infertility participated in the study and 23 of them conceived. Psychological evaluation included background questionnaires, Lubins Depression Adjective Check List, and Spielbergers State Trait Anxiety inventory. Cortisol and prolactin levels were estimated by radioimmunoassay. The results showed that patients anxiety and depression scores were significantly higher than the population norm. Psychological test scores and hormonal levels showed a similar pattern of change, increasing on oocyte retrieval day, decreasing on embryo transfer day, and rising again on pregnancy test day. Differences between these phases were generally significant. Differences in parameters means between conceiving (C) and nonconceiving (NC) women were generally not significant. However, correlations between psychological measures and hormonal levels showed a clear disparity between C and NC women in the last phase. Whereas significant negative correlations were found in C patients, no relationship was found in NC patients. The findings suggest that success in IVF treatment may depend, in part, on differential modes of coping with anxiety and depression, involving hormonal or endorphin mediation.

INCREASED RISK OF BREAST CANCER AFTER LOW-DOSE IRRADIATION

A significant increase in the risk of breast cancer has been found for the most recent 5-year period of a long-term follow-up study of children subjected to scalp irradiation, in whom a carcinogenic effect was previously only apparent in the head and neck. This increased risk was found among women aged 5 to 9 years at exposure. The breast had been exposed to a low radiation dose of approximately 16 mGy.

Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in israel

OBJECTIVEnThe objective was to evaluate the prevalence of BRCA1/2 mutations in selected categories of ovarian cancer patients in Israel.nnnMETHODSnBlood samples and specimens of ovarian tumors were obtained in the course of a national case control study of women with ovarian cancer in Israel. Eight hundred ninety-six patients with epithelial ovarian cancer, 40 cases with nonepithelial ovarian cancer, and 68 with primary peritoneal cancer were tested for the BRCA mutations. Analysis of the three common BRCA mutations in Israel (185delAG, 5382insC in BRCA1, and 6174delT in BRCA2) was done using a multiplex polymerase chain reaction assay. A multivariate logistic regression model was used to assess the association of mutation carrier status and other factors (age, origin, family history, and clinical variables).nnnRESULTSnOf the 779 invasive epithelial ovarian cancer cases, 29.4% were mutation carriers. The prevalence of the mutations was higher among women below age 60 and in more advanced cases. The prevalence was low in mucinous tumors. There was almost a twofold excess of mutations among women with positive family history (45.7%), but still 26.5% of the family history negative cases were carriers. As expected, we found a higher rate of mutation carriers among the Ashkenazi group (34.2%) and 55% among Ashkenazi women with positive family history. No subjects born in North Africa were mutation positive.nnnCONCLUSIONnBRCA mutations are strongly associated with ovarian cancer and they are present in variable rates in distinct age, ethnic, and histopathologic categories.

Increased risk of salivary gland tumors after low-dose irradiation.

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow‐up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow‐up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long‐term follow‐up of patients who have been subjected to head and neck radiation.

Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans.

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case‐control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0–19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population‐based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the childs age at diagnosis, the histologic type of tumor or center.

Selected risk factors for transitional cell bladder cancer

Cancer of the bladder has long been associated with environmental risk factors, such as occupational hazards and smoking. The aim of the current study was to evaluate the contribution of known risk factors on a community basis in the 1990s, in view of the recent worldwide efforts to control environmental hazards. The study population included 140 male patients and 280 matched controls. Information on demographic data, occupational exposure, smoking habits and disease history was obtained by personal interviews. Our study confirmed the role of industrial occupation (OR=2.21; 95% Cl=1.21−4.02) and exposure to 3 or more metals (OR=3.65; 95% Cl=1.21−11.08) as risk factors. Prostate enlargement was also found significant, but probably not causal (OR=2.23;95% Cl=1.29−3.87). Surprisingly, smoking showed only an inconsistent association with higher rates among those who started to smoke before 18 years of age (OR=2.64; 95% Cl=1.4−4.99) and those who smoked more than 30 cigarettes per day (OR=1.82; 95% Cl=0.95−3.49). The above data suggest that current efforts to reduce the load of bladder cancer in the population, via environmental measures, have not as yet yielded significant effects.

The limitations of using hospital controls in cancer etiology - One more example for Berkson's bias

The aim of this report was to present an example in which Berksons bias, most probably, affected the results of a study by overriding the influence of a well-established risk factor (smoking) in the etiology of bladder cancer. The results of a study of 140 male patients with bladder cancer and 280 matched hospital controls confirmed the etiological role of industrial occupation in bladder cancer but failed to confirm the role of smoking. We reanalyzed the proportion of chronic related morbidity as well as the rate of smoking in patients with lung disease in cases and controls. A similar distribution of some chronic diseases known to be highly associated with smoking was found among cases and controls. Highest smoking rates (91%) were found among patients with bladder cancer who also reported a concomitant lung disease, and the lowest rate (67%) was noted among controls without lung disease (p = 0.009). Using the prevalence of smoking in the general Israeli male population (50%), significant odds ratio for bladder cancer among ever smokers compared to never smokers was observed. Our conclusion is that a possibility of Berksons bias should be considered whenever hospital controls are used. Information on diseases related to the risk factor under consideration and on the prevalence of the risk factor in the general population, may demonstrate the existence of such a bias.

The quandary of cancer prevention

The incidence and mortality due to the major cancers such as lung, breast, colon-rectum, prostate, and ovary have changed very little over the past 20-30 years, in spite of the introduction of important new treatments and apparent prolongation of survival of patients with these cancers. The new strategies focus on earlier detection and primary prevention of cancer. Three approaches for prevention are receiving increasing prominence as an approach to reducing the incidence of cancer: (1) control of common source environmental carcinogens, (2) modification of personal health behavior believed to increase or decrease the risk of cancer, and (3) identification of specific genotypes that increase the risk of cancer. All of these approaches offer some hope of reducing cancer incidence and morbidity. All will be costly and, therefore, require careful evaluation. It is likely that the changes in personal health behaviors will have the greatest overall impact on cancer incidence. Identification of specific genotypes will be of importance for high risk families. At present, it is unlikely that control of environmental common sources will substantially reduce cancer incidence without better measures of exposure and risk of disease.