Self-reported diagnostic X-ray investigation and data from medical records in case-control studies on thyroid cancer: evidence of recall bias?

The aim of the present investigation was to evaluate and compare data from medical records with mailed questionnaires concerning risk factors for diagnostic X-ray investigation induced thyroid cancer. This study encompassed 180 patients and 360 controls, selected from the National Population Registry. Information on medical X-ray exposure was obtained by medical records and also from mailed questionnaires, with a latency of 5 years from diagnosis. The mailed questionnaire was answered by 171 cases (95%) and 325 controls (90%). In 132 cases and 251 controls data on medical records were collected and compared with data from mailed questionnaires for the same subjects. No earlier X-ray investigation based upon medical records was reported in 39 cases and in 74 controls. The median cumulative thyroid dose for cases was 1.1 mGy in medical records and in mailed questionnaire 0.6 mGy. For the controls the respective median cumulative dose was 1.0 mGy in medical records and 0.3 mGy in mailed questionnaires. The median ratio between medical records and mailed questionnaires in the cases was 2.1. For the controls the median ratio was 2.9. Wilcoxon's Matched Pairs Test (WMPT) showed a significantly underreport of thyroid X-ray dose in both cases (P<0.01) and controls (P<0.000001). In cases younger than 50 years at the time of the diagnosis of thyroid cancer there was not a significant underreport of X-ray examinations. Corresponding data from the control group showed however a significant underreport. Both cases and controls older than 50 reported significantly fewer X-ray investigations compared with data from medical records. A significant underreport was found among women both in cases and controls. For men there was a slight underreport among both cases and controls, although not significant. In conclusion, when studying diagnostic X-ray investigation as a risk factor for thyroid cancer, it is important to reduce the potential for recall bias when the study relies only on case-control reporting. To complement a case-control study with prospective medical data recorded at the time of the investigation could be an appropriate way to reduce the risk for recall bias.

No association between the use of cellular or cordless telephones and salivary gland tumours.

AIM: To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours. METHODS: Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included. RESULTS: There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years. CONCLUSIONS: No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.

Cellular and cordless telephones and the risk for brain tumours.

Microwave exposure from the use of cellular telephones has been discussed in recent years as a potential risk factor for brain tumours. We included in a case-control study 1617 patients aged 20-80 years of both sexes with brain tumour diagnosed between 1 January 1997 and 30 June 2000. They were alive at the study time and had histopathologically verified brain tumour. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. Exposure was assessed by a questionnaire that was answered by 1429 (88%) cases and 1470 (91%) controls. In total, use of analogue cellular telephones gave an increased risk with an odds ratio (OR) of 1.3 (95% confidence interval (CI) 1.02-1.6). With a tumour induction period of >10 years the risk increased further: OR 1.8 (95% CI 1.1-2.9). No clear association was found for digital or cordless telephones. With regard to the anatomical area of the tumour and exposure to microwaves, the risk was increased for tumours located in the temporal area on the same side of the brain that was used during phone calls; for analogue cellular telephones the OR was 2.5 (95% CI 1.3-4.9). Use of a telephone on the opposite side of the brain was not associated with an increased risk for brain tumours. With regard to different tumour types, the highest risk was for acoustic neurinoma (OR 3.5, 95% CI 1.8-6.8) among analogue cellular telephone users.

A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption.

OBJECTIVE: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. METHODS: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. RESULTS: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromsø, and Vaud. Conversely, the ORs for the studies in Los Angeles. Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88). CONCLUSION: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.

Medical diagnostic X-ray radiation--an evaluation from medical records and dentist cards in a case-control study of thyroid cancer in the northern medical region of Sweden.

The aim of this study was to evaluate the association between thyroid cancer and diagnostic X-ray radiation based on medical records. By using the Swedish Cancer Registry, 187 living cases with thyroid cancer (81%), aged 20-70 years at the time of their diagnosis in 1980-1989 were identified in the Northern Health Care Region of Sweden. Seven cases were reclassified as having a disease other than thyroid cancer and were excluded. The investigation included 180 living cases and 360 controls from the National Population Registry. In 132 cases and 251 controls data from X-ray records on earlier investigations > 5 years prior to diagnosis and corresponding years for the controls were analysed. The mean calculated thyroid dose for the cases was 7.0 mGy (median 1.1) and for the controls 7.4 mGy (median 1.0). This study showed no difference in the total material between calculated absorbed thyroid dose of medical diagnostic X-ray in cases versus controls. In younger women (< or = 50 years at diagnosis) with papillary thyroid cancer an association was found, however it was not significant. The results could be related to selective bias and should be treated with caution. Future studies require analysis of diagnostic medical X-ray investigations involving the thyroid gland including more specific data on sex and age of exposure in the whole study group.

Ionizing radiation, cellular telephones and the risk for brain tumours.

A case-control study on brain tumours included 233 patients aged 20-80 years and alive at the study time. They had histopathologically verified brain tumour and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register. Two hundred and nine cases (90%) and 425 controls (91%) answered the questionnaire. Results are presented for the whole study group, as given here, and for malignant and benign tumours separately. For workers in the chemical industry the odds ratio (OR) was 4.10, 95% confidence interval (95% CI) 1.25-13.4 and laboratory workers OR 3.21, 95% CI 1.16-8.85. Radiotherapy of the head and neck region gave OR 3.61, 95% CI 0.65-19.9. Medical diagnostic X-ray of the same area yielded OR 1.64, 95% CI 1.04-2.58. Work as a physician gave OR 6.00, 95% CI 0.62-57.7. All three cases had worked with fluoroscopy. Ipsilateral (same side) use of a cellular telephone increased the risk of tumours in the temporal, temporoparietal and occipital areas, with OR 2.42, 95% CI 0.97-6.05 (i.e. the anatomical areas with highest exposure to microwaves from a mobile phone).

Case-control study on radiology work, medical x-ray investigations, and use of cellular telephones as risk factors for brain tumors.

CONTEXT: Ionizing radiation is a well-established risk factor for brain tumors. During recent years, microwave exposure from the use of cellular telephones has been discussed as a potential risk factor. OBJECTIVE: To determine risk factors for brain tumors. DESIGN: A case-control study, with exposure assessed by questionnaires. PARTICIPANTS: A total of 233 currently living men and women, aged 20 to 80 years, were included. The case patients had histopathologically verified brain tumors and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register. MAIN OUTCOME MEASURES: Ionizing radiation and use of cellular telephones as risk factors for brain tumors. RESULTS: A total of 209 cases (90%) and 425 controls (91%) answered the questionnaire. Work as a physician yielded an odds ratio (OR) of 6.00, with a 95% confidence interval (CI) of 0.62 to 57.7. All three case patients had worked with fluoroscopy. Radiotherapy of the head and neck region yielded an OR of 3.61 (95% CI, 0.65-19.9). Medical diagnostic x-ray examination of the same area yielded an OR of 2.10 (95% CI, 1.25-3.53), with a tumor induction period of 5 years or more. Chemical industry work yielded an OR of 4.10 (95% CI, 1.25-13.4), and laboratory work yielded an OR of 3.21 (95% CI, 1.16-8.85). Ipsilateral use of cellular telephones increased the risk for tumors in the temporal, temporoparietal, and occipital lobes (OR, 2.42; 95% CI, 0.97-6.05), ie, the anatomic areas with highest exposure to microwaves from a mobile telephone. The result was further strengthened (OR, 2.62; 95% CI, 1.02-6.71) in a multivariate analysis that included laboratory work and medical diagnostic x-ray investigations of the head and neck. CONCLUSION: Exposure to ionizing radiation, work in laboratories, and work in the chemical industry increased the risk of brain tumors. Use of a cellular telephone was associated with an increased risk in the anatomic area with highest exposure.

A pooled analysis of thyroid cancer studies. V. Anthropometric factors.

OBJECTIVE: To assess the relation between anthropometric factors and thyroid cancer risk in a pooled analysis of individual data from 12 case-control studies conducted in the US, Japan, China and Europe. METHODS: 2056 female and 417 male cases, 3358 female and 965 male controls were considered. Odds ratios (OR) were derived from logistic regression, conditioning on age, A-bomb exposure (Japan) and study, and adjusting for radiotherapy. RESULTS: Compared to the lowest tertile of height, the pooled OR was 1.2 for females for the highest one, and 1.5 for males, and trends in risk were significant. With reference to weight at diagnosis, the OR for females was 1.2 for the highest tertile, and the trend in risk was significant, whereas no association was observed in males. Body mass index (BMI) at diagnosis was directly related to thyroid cancer risk in females (OR = 1.2 for the highest tertile), but not in males. No consistent pattern of risk emerged with BMI during the late teens. Most of the associations were observed both for papillary and follicular cancers, and in all age groups. However, significant heterogeneity was observed across studies. CONCLUSIONS: Height and weight at diagnosis are moderately related to thyroid cancer risk.

Use of cellular telephones and the risk for brain tumours: A case-control study.

The use of cellular telephones has increased dramatically during the 1990's in the world. In the 1980's the analogue NMT system was used whereas the digital GSM system was introduced in early 1990's and is now the preferred system. Case reports of brain tumours in users initiated this case-control study on brain tumours and use of cellular telephones. Also other exposures were assessed. All cases, both males and females, with histopathologically verified brain tumour living in Uppsala-Orebro region (1994-96) and Stockholm region (1995-96) aged 20-80 at the time of diagnosis and alive at start of the study were included, 233 in total. Two controls to each case were selected from the Swedish Population Register matched for sex, age and study region. Exposure was assessed by questionnaires supplemented over the phone. The analyses were based on answers from 209 (90%) cases and 425 (91%) controls. Use of cellular telephone gave odds ratio (OR) = 0.98 with 95% confidence interval (CI) = 0. 69-1.41. For the digital GSM system OR = 0.97, CI = 0.61-1.56 and for the analogue NMT system OR = 0.94, CI = 0.62-1.44 were calculated. Dose-response analysis and using different tumour induction periods gave similar results. Non-significantly increased risk was found for tumour in the temporal or occipital lobe on the same side as a cellular phone had been used, right side OR = 2.45, CI = 0.78-7.76, left side OR = 2.40, CI = 0.52-10.9 Increased risk was found only for use of the NMT system. For GSM use the observation time is still too short for definite conclusions. An increased risk for brain tumour in the anatomical area close to the use of a cellular telephone should be especially studied in the future.

A pooled analysis of case-control studies of thyroid cancer. I. Methods.

OBJECTIVE: Because the etiology of thyroid cancer is not well described, we conducted a pooled analysis of all published case-control studies, as well as two identified unpublished studies. This paper describes the major characteristics of the 14 studies included in the analysis, as well as the statistical methods employed. Four studies were conducted in the United States (1 each in Washington State, California, Connecticut and Hawaii), 8 in Europe (3 in Sweden, 2 in Norway, 1 in Switzerland, 1 in Italy and 1 in Greece), and 2 in Asia (1 in China and 1 in Japan). METHODS: The original datasets were obtained and restructured in a uniform format. Data on socio-demographic characteristics, anthropometric measures, smoking and alcohol consumption, history of benign thyroid diseases and of other selected medical conditions and treatments, family history of cancer and of benign thyroid conditions, occupation, residence in endemic goitre areas, and dietary habits were analyzed. For women, we also analyzed menstrual and reproductive factors and use of female hormones. Radiotherapy and, in Japan, exposure to the A-bombs were considered as potential confounding factors. RESULTS: A total of 2,725 cases (2,247 females and 478 males) and 4,776 controls (3,699 females and 1,077 males) were included in this study. Of the cases, 79% were classified as papillary thyroid carcinomas, 14% as follicular, 2% medullary, 1% anaplastic, 1% other histologies, and 3% histological type unknown. Each of the datasets was checked for outliers and consistency. Data were analysed separately by study center, gender, and the two major histologic types (papillary, follicular). Frequency tables and simple statistics were computed for each variable under study. Conditional logistic regression was used to compute odds ratios. For matched studies, the original matching was preserved, whereas, for unmatched ones, five-year age groups were used for matching. Study-specific analyses were computed, and then the data from all the studies were pooled conditioning on study. Heterogeneity between studies, geographic areas and study designs was assessed, and the modifying effect of age was also evaluated.

A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones.

OBJECTIVE: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe. METHODS: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity. RESULTS: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment. CONCLUSIONS: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.

A pooled analysis of case-control studies of thyroid cancer. IV. Benign thyroid diseases.

OBJECTIVE: To obtain more precise estimates of the association between thyroid cancer and benign thyroid diseases and to elucidate the role of potential confounders or effect modifiers. METHODS: The original data from 12 case-control studies from the United States, Asia, and Europe were pooled. Based on 2,094 women and 425 men with cancer of the thyroid and, respectively, 3,248 and 928 control subjects, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age and radiotherapy. RESULTS: A history of hypothyroidism was not associated with cancer risk (pooled ORs = 0.9, 95% confidence interval, CI: 0.7-1.3 in women and 1.7, 95% CI: 0.3-11.7 in men). ORs for hyperthyroidism were 1.4 (95% CI: 1.0-2.1) in women and 3.1 (95% CI: 1.0-9.8) in men. In women, however, risk was lower in the absence of or after allowance for history of goiter. Pooled ORs for a history of goiter were 5.9 (95% CI: 4.2-8.1) in women and 38.3 (95% CI: 5.0-291.2) in men. Risk for a history of benign nodules/adenomas was especially high (OR = 29.9, 95% CI: 14.5-62.0, in women; 18 cases versus 0 controls in men). The excess risk for goiter and benign nodules/adenomas was greatest within 2-4 years prior to thyroid cancer diagnosis, but an elevated OR was present 10 years or more before cancer. CONCLUSIONS: Goiter and benign nodules/adenomas are the strongest risk factors for thyroid cancer, apart from radiation in childhood.

Diagnostic X-ray exposure and female papillary thyroid cancer: a pooled analysis of two Swedish studies.

The aim of the present study was to evaluate the risk for female papillary thyroid cancer from occupational and medical low level radiation exposure. The analyses are based on data from two Swedish case-control studies on determinants for thyroid cancer. One hundred and eighty six thyroid cancer cases, diagnosed during 1977-89 and aged 20-70 years, were collected from cancer registers. Twice as many population controls were selected. Questionnaires were mailed in 1990-91 to living cases and controls. A high risk was found for the occupational group of dentists/dental assistants, odds ratio (OR) = 13.1, 95% confidence interval (CI) = 2.1-389. For all occupational exposure to X-rays OR = 2.1, 95% CI = 1.0-4.4 was obtained. Diagnostic X-ray exposure was associated with increased risk, with a dose-response tendency yielding OR = 2.6, 95% CI = 1.5-5.1 for the highest absorbed thyroid dose (> 1.0 mGy). If only females of 50 years or less at diagnosis were considered, higher ORs were obtained. Increased risks were also found for some site-specific examinations, some of them giving very low radiation dose to the thyroid; more than 10 dental X-rays gave OR = 3.5, 95% CI = 1.6-7.6. A potentiated risk for prior X-rays was seen among women with three or more parities, with OR = 4.7, 95% CI = 1.5-14.8. Exposure to visual display units yielded OR = 2.3, 95% CI = 0.9-5.6. As in all questionnaire-based case-control studies possible recall bias must be considered but is unlikely to cause dose-response patterns and interaction as indicated in this study.

No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation.

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.

Occupation and female papillary cancer of the thyroid.

This article presents the joint results of two Swedish case-control studies regarding occupational exposure and female papillary thyroid cancer. Questionnaires inquiring about lifetime occupations and specific occupational exposures were mailed to cases and controls, aged 20 to 70 years. Some 185 female papillary or mixed cancer cases and 426 female controls were included in the analysis. Increased risks were seen for women who had worked as a dentist/dental assistant, teacher, shoemaker, or warehouse worker. In addition, occupational contacts with undefined chemicals, x-rays, or video display terminals were indicated as risk factors.

Thyroid cancer: reproductive factors, previous diseases, drug intake, family history and diet. A case-control study.

An association between female sex hormones and thyroid cancer has been suggested, but the only well-established risk factor is ionizing radiation. This case-control study was designed to evaluate the association between different aetiological factors and thyroid cancer and encompassed 180 cases aged 20-70 years at the time of diagnosis in 1980-89, and 360 controls. The response rate was 92%. A history of one pregnancy gave increased risk for papillary thyroid cancer, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.0-11, whereas no increased risk was found for > or = four pregnancies. Age > or = 25 years at the time of the first pregnancy showed a non-significantly increased risk for papillary thyroid cancer, OR = 1.5, 95% CI = 0.8-3.0. Use of oral contraceptives before the age of 20 years gave an OR of 0.5, 95% CI = 0.1-1.3. A history of asthma or allergy, or the use of cortisone, significantly decreased the risk, while cardiovascular disease in men increased the risk of developing thyroid cancer. In the logistic regression, use of cortisone decreased the risk, while one pregnancy gave a significantly increased risk in papillary thyroid cancer. The results indicated that endogenous hormones may play a role in the aetiology of thyroid cancer in women.

Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group.

BACKGROUND: Anaplastic carcinoma of the thyroid (ACT) rarely can be cured, but every effort should be made to improve prognosis and, above all, prevent death due to suffocation or large local tumor ulceration. METHODS: From 1984 to 1992, 33 consecutive patients with ACT were treated prospectively according to a combined treatment program consisting of hyperfractionated radiotherapy, doxorubicin, and debulking surgery. Preoperative radiotherapy was administered to a target dose of 30 Gy and postoperatively to a total dose of 46 Gy. Radiotherapy was performed 5 days a week. The daily fraction was 1.0 Gy x 2 until 1988, after which it was 1.3 Gy x 2. Otherwise, the therapy remained unchanged. Twenty milligrams of doxorubicin were administered intravenously per week. Debulking surgery was possible in 23 patients (70%). RESULTS: No patient failed to complete the protocol because of toxicity. There were no signs of local recurrence in 16 patients (48%). In only eight patients (24%) was death attributed to local failure. In four patients, survival with no evidence of disease exceeded 2 years. Improvement in local tumor control was marginally significant (P = 0.08) in the 17 patients treated in the latter part of the study, with no sign of local disease in 11 patients and deaths due to local failure in only 2 patients. The improved local control could not be attributed to any differences between the two series. CONCLUSION: Combination modality treatment of ACT is feasible and effective despite the patients' advanced age and locally advanced disease. There was a tendency for local control to be improved after accelerated radiotherapy.