Sigrid Lönn

Acoustic neuroma risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study

BACKGROUND The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. METHODS A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. RESULTS The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for ≥10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (≥1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with ≥1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for ≥10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for ≥1640 h of cumulative call time it was 2.79 (1.51-5.16), but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. CONCLUSIONS There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one.

Prognostic value of erb-B2 and myc amplification in breast cancer imprints

Background. Amplification of erb‐B2 and myc shows prognostic value in patients with operable breast cancer. Amplification is usually detected in tumor samples remaining after pathologic work‐up, preventing the examination of small tumors.

Gene Amplification Detected in Carcinoma Cells from Human Urinary Bladder Washings by the Polymerase Chain Reaction Method

Background. Urinary bladder carcinoma often is diagnosed from malignant cells in bladder washings obtained at cystoscopic examination. In some cases, there are difficulties distinguishing between cytologic Grades 1 and 2. Detection of genetic alterations in combination with morphologic analysis may facilitate the diagnosis.

Medical history, cigarette smoking and risk of acoustic neuroma: An international case‐control study

Acoustic neuroma (vestibular schwannoma) is a benign tumor of the vestibulocochlear nerve. Its recorded incidence is increasing but risk factors for this tumor have scarcely been investigated. We conducted a population‐based case‐control study of risk factors for acoustic neuroma in the UK and Nordic countries, including 563 cases and 2,703 controls. Tumor risk was analyzed in relation to medical history and cigarette smoking. Risk of acoustic neuroma was significantly raised in parous compared with nulliparous women (OR = 1.7, 95% CI: 1.1–2.6), but was not related to age at first birth or number of children. Risk was not associated with a history of allergic disease, past head injury, past diagnosis of a neoplasm or birth characteristics, but was significantly raised for past diagnosis of epilepsy (OR = 2.5, 95% CI: 1.3–4.9). Tumor risk was significantly reduced in subjects who had ever regularly smoked cigarettes (OR = 0.7, 95% CI: 0.6–0.9), but the reduction applied only to current smokers (OR = 0.5, 95% CI: 0.4–0.6), not ex‐smokers (OR = 1.0, 95% CI: 0.8–1.3). The reduced risk of acoustic neuroma in smokers and raised risk in parous women might relate to sex hormone levels, or smoking might suppress tumor growth, but effects of parity and smoking on timing of diagnosis of the tumor are also a potential explanation. The raised risk in relation to past diagnosis of epilepsy might be a surveillance artefact or imply that epilepsy and/or antiepileptic medication use predispose to acoustic neuroma. These findings need replication by other studies and possible mechanisms need to be clarified.

Higher frequency of gene amplification in breast cancer patients who received adjuvant chemotherapy

Amplification of certain genes is involved in resistance to chemotherapy. The development of such amplification in patients by drug treatment has not yet been established. We have assessed the appearance of gene amplification in breast cancer patients with recurrent disease. One group of patients had previously received adjuvant chemotherapy (cyclophosphamide, methotrexate, 5‐fluorouracil [CMF]) after surgery. The second group had not. All of these patients had developed recurrent disease and were receiving first‐line endocrine treatment (tamoxifen).

Detection and temporal appearance of multiple copies of c-erb-B2 genes in advanced mammary carcinoma using fine needle biopsies and the polymerase chain reaction

Aspiration of tumor cells by the fine-needle biopsy method yields only a small number of cells, which hampers conventional molecular analysis for the presence of multiple copies of oncogenes. We have therefore adopted the polymerase chain reaction (PCR) method to study semi-quantitatively the level of the c-erb-B2 gene in human breast tumor samples. Of 39 patients with mammary carcinoma, 7 (19%) contained multiple copies of c-erb-B2 genes, whereas only two samples failed to give informative data. Next the temporal appearance of multiple gene copies was examined in 20 patients with clinical stage IV disease. Tumor samples were obtained every second to third month from the same tumor lesion of each patient. None of the initial samples from each patient contained multiple copies of c-erb-B2. Of 16 patients that showed progressive clinical disease, 5 developed multiple gene copies, showing that the event occurs in clinical stage IV disease.

Breast cancer: prognostic significance of c-erb-B2 and int-2 amplification compared with DNA ploidy, S-phase fraction, and conventional clinicopathological features

SummaryThe prognostic value of oncogene amplification and conventional clinicopathological features was determined in consecutive breast cancers detected during 5 months in 1975–1976 in 4 Swedish counties. Material was collected from 162 of the 179 patients and tumor size, nodal status, FSH, estrogen/progesterone receptor status, DNA ploidy and S-phase fraction determined. Tissues remaining from 80 patients were stored frozen until 1991, when amplification of the oncogenes c-erb-B2 and int-2 was determined. We show that c-erb-B2 amplification (but not int-2 amplification) and positive axillary nodal status show prognostic significance for both survival and relapse-free survival in univariate and multivariate analysis. The other examined factors showed no significance.

C‐ERB‐B2/INT‐2 amplification appears faster in breast‐cancer patients receiving second‐line endocrine treatment

We have examined the appearance of c‐erb‐b2 and int‐2 amplification in 2 different groups of breast‐cancer patients. The groups differed with regard to their clinical status in that one group was receiving first‐line endocrine treatment (tamoxifen) whereas the second was receiving second‐line endocrine treatment (after failing on tamoxifen). The latter group of patients showed clinically a more advanced disease (higher frequency of stage‐IV as compared to stage‐III disease). Consecutive tumor samples were obtained using fine‐needle biopsies from individual tumor lesions of each patient every second or third month. Median time from diagnosis to the last biopsy for patients receiving tamoxifen was 25 months and, for patients receiving second‐line treatment, 55 months. The presence of amplification was determined using semi‐quantificative PCR. We found that both genes developed amplification during tumor progression. The appearance of amplification was more pronounced in the clinically more advanced patients receiving second‐line treatment (p = 0.018).

Progressive formation of DNA lesions during treatment with anti-metabolites without incorporation of the drugs into DNA.

Anti-metabolites, such as methotrexate, 5-fluoropyrimidines or hydroxyurea, induce progressive formation of DNA lesions. 5-Fluoropyrimidines induce DNA lesions either by incorporation of the drug into DNA or by a mechanism not involving incorporation. The second mechanism, not involving incorporation, is also seen with methotrexate and hydroxyurea. The three anti-metabolites have in common their ability to reduce intracellular levels of nucleotides, resulting in reduced efficiency of repair of DNA lesions. The lesions probably appear spontaneously, independently of the drug treatment.

Prognostic significance of c-erb-B2 amplification in fine-needle biopsies of breast cancer patients not operated at diagnosis

Prognostication of breast cancer patients, not operated at diagnosis, poses a clinically difficult problem. To use gene amplification we examined cytological samples and determined c-erb-B2 gene copy number with semiquantitative PCR. Control experiments showed the same gene-copy number in aliquots that were either air-dried (and MGG-stained), fixed in methanol (and air-dried), or snap-frozen in liquid nitrogen. Therefore we examined the prognostic value of c-erb-B2 amplification in 95 breast cancer patients that had not been operated at diagnosis (up to 12 years previously). Tumor cells were obtained from routine archival cytological smears. 15 patients (16%) had developed amplification. Univariate and multivariate analysis showed that c-erb-B2 amplification is a significant prognostic factor (p < 0.0001). Hence routine cytological MGG smears can be used for prognostic determination.