Arne Hallquist

A pooled analysis of case–control studies of thyroid cancer: cigarette smoking and consumption of alcohol, coffee, and tea

Objective: To analyze the role of smoking, alcohol, coffee and tea in relation to thyroid cancer, we conducted a pooled analysis of 14 case–control studies conducted in the United States, Europe, and Asia. Methods: The sample consisted of 2725 thyroid cancer cases (2247 females, 478 males) and 4776 controls (3699 females, 1077 males). Conditional logistic regression with stratification on study, age at diagnosis, and gender was used to compute odds ratios and 95% confidence intervals. Results: Thyroid cancer risk was reduced in persons who had ever smoked. The relationship was more pronounced in current smokers (OR = 0.6, 95% CI = 0.6–0.7) than former smokers (OR = 0.9, 95% CI = 0.8–1.1). There were significant trends of reduced risk with greater duration and frequency of smoking. For consumption of wine and beer, there was a significant trend of decreasing thyroid cancer risk (p = 0.02) that was not maintained after adjustment for current smoking (p = 0.12). Thyroid cancer risk was not associated with consumption of coffee or tea. These findings were consistent in both gender-specific and histology-specific (papillary and follicular) analyses. Conclusions: Pooled analyses of these geographically diverse case–control data indicate a reduced thyroid cancer risk associated with current smoking. A reduced risk associated with alcohol was eliminated after adjustment for smoking, and caffeinated beverages did not alter thyroid cancer risk.

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-Örebro, 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. 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 2094 women and 425 men with cancer of the thyroid and, respectively, 3248 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.

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-Örebro 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).

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

AbstractObjective: 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.

Leukaemia incidence after iodine-131 exposure

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

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.

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 (CD = 1.0–11, whereas no increased risk was found for ≥ four pregnancies. Age ≥ 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.

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.

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.