Pia K. Verkasalo

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

BACKGROUND The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. METHODS We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. RESULTS At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). CONCLUSIONS Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites suggests major gaps in our knowledge of the genetics of cancer.

A pooled analysis of magnetic fields and childhood leukaemia

Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Risk of cancer in Finnish children living close to power lines.

OBJECTIVE--To investigate the risk of cancer in children living close to overhead power lines with magnetic fields of > or = 0.01 microteslas (microT). DESIGN--Cohort study. SETTING--The whole of Finland. SUBJECTS--68,300 boys and 66,500 girls aged 0-19 years living during 1970-89 within 500 m of overhead power lines of 110-400 kV in magnetic fields calculated to be > or = 0.01 microT. Subjects were identified by record linkages of nationwide registers. MAIN OUTCOME MEASURES--Numbers of observed cases in follow up for cancer and standardised incidence ratios for all cancers and particularly for nervous system tumours, leukaemia, and lymphoma. RESULTS--In the whole cohort 140 cases of cancer were observed (145 expected; standardised incidence ratio 0.97, 95% confidence interval 0.81 to 1.1). No statistically significant increases in all cancers and in leukaemia and lymphoma were found in children at any exposure level. A statistically significant excess of nervous system tumours was found in boys (but not in girls) who were exposed to magnetic fields of > or = 0.20 microT or cumulative exposure of > or = 0.40 microT years. CONCLUSIONS--Residentia magnetic fields of transmission power lines do not constitute a major public health problem regarding childhood cancer. The small numbers do not allow further conclusions about the risk of cancer in stronger magnetic fields.

Sleep Duration and Breast Cancer: A Prospective Cohort Study

Breast cancer incidence has increased during recent decades for reasons that are only partly understood. Prevalence of sleeping difficulties and sleepiness has increased, whereas sleeping duration per night has decreased. We hypothesized that there is an inverse association between sleep duration and breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. This population-based study includes information from women born in Finland before 1958. Sleep duration, other sleep variables, and breast cancer risk factors were assessed by self-administered questionnaires given in 1975 and in 1981. Breast cancer incidence data for 1976 to 1996 was obtained from the Finnish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox proportional hazards models adjusting for potential confounders. Altogether, 242 cases of breast cancer occurred over the study period among the 12,222 women with sleep duration data in 1975. For these women, the HRs for breast cancer in the short (< or =6 hours), average (7-8 hours), and long sleep (> or =9 hours) duration groups were 0.85 (CI, 0.54-1.34), 1.0 (referent), and 0.69 (CI, 0.45-1.06), respectively. Analysis restricted to the 7,396 women (146 cases) whose sleep duration in 1975 and 1981 were in the same duration group (stable sleepers) yielded HRs of 1.10 (CI, 0.59-2.05), 1.0, and 0.28 (CI, 0.09-0.88), with a decreasing trend (P = 0.03). This study provides some support for a decreased risk of breast cancer in long sleepers.

Genetic predisposition, environment and cancer incidence: A nationwide twin study in Finland, 1976–1995

Twin studies integrate genetic and environmental (including physical environment and life‐style) information by comparing monozygotic and dizygotic twins for the occurrence of disease. Our objectives were to compare cancer incidence in twins with national rates and to estimate both the probability that co‐twins of affected twins may develop cancer and the importance of genetic predisposition and environment in cancer development. The nationwide record linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow‐up of 12,941 same‐sexed twin pairs for incident primary cancers from 1976 to 1995. Zygosity was determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting of structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that among the general population. Monozygotic co‐twins of affected twins were at 50% higher risk than were dizygotic co‐twins. Based on genetic modeling, inherited genetic factors accounted for 18% (95% confidence interval 4–32%) of the liability in inter‐individual variation in the risk of overall cancer, while non‐genetic factors shared by twins accounted for 7% (0–16%) and unique environmental factors for 75% (65–85%). Our results appear to exclude a contribution greater than one‐third for genetic predisposition in the development of cancer in the general population, thus pointing to the earlier confirmed substantial role of environment. Int. J. Cancer 83:743–749, 1999.

Inverse association between breast cancer incidence and degree of visual impairment in Finland

SummaryA total of 10 935 women with visual impairment were identified from the Finnish Register of Visual Impairment and followed up for cancer through the Finnish Cancer Registry for years 1983–1996. Breast cancer risk decreased by degree of visual impairment (P for trend 0.04) which suggests a dose–response relationship between visible light and breast cancer risk.

Magnetic fields of high voltage power lines and risk of cancer in Finnish adults: nationwide cohort study

Abstract Objective: To investigate the risk of cancer in association with magnetic fields in Finnish adults living close to high voltage power lines. Design: Nationwide cohort study. Subjects: 383 700 people who lived during 1970–89 within 500 metres of overhead power lines of 110–400 kV in a magnetic field calculated to be >/=0.01 μT. Study subjects were identified by record linkages of nationwide registers. Main outcome measures: Numbers of observed and expected cases of cancer, standardised incidence ratios, and incidence rate ratios adjusted for sex, age, calendar year, and social class—for example, by continuous cumulative exposure per 1 μT year—with 95% confidence intervals from multiplicative models for all cancers combined and 21 selected types. Results: Altogether 8415 cases of cancer were observed (standardised incidence ratio 0.98; 95% confidence interval 0.96 to 1.00) in adults. All incidence rate ratios for both sexes combined were non-significant and between 0.91 and 1.11. Significant excesses were observed in multiple myeloma in men (incidence rate ratio 1.22) and in colon cancer in women (1.16). Conclusions: Typical residential magnetic fields generated by high voltage power lines do not seem to be related to the risk of overall cancer in adults. The previously suggested associations between extremely low frequency magnetic fields and tumours of the nervous system, lymphoma, and leukaemia in adults and breast cancer in women were not confirmed. Key messages The present population based cohort study among Finnish adults with 8500 observed cancer cases found no increase in the risk of overall cancer in adults exposed to magnetic fields of high voltage power lines The previously suggested associations between magnetic fields and tumours of the nervous system, lymphoma, leukaemia, and breast cancer in women were not confirmed The results of the present study suggest strongly that typical residential magnetic fields generated by high voltage power lines are not related to cancer in adults The possibility of an increase in risk at higher magnetic field levels, or in more specific cancer subtypes, cannot be excluded on the basis of this study

Lifestyle differences in twin pairs discordant for basal cell carcinoma of the skin

Summary Background Basal cell carcinoma (BCC) of the skin is a multifactorial disease with a complex interplay of genetic, environmental and lifestyle factors, including patterns of solar exposure, with childhood exposure being of particular relevance. Case–control studies in disease‐discordant twin pairs adjust for familial factors and improve the power of conventional case–control studies.

Subsequent primary cancers after basal-cell carcinoma: A nationwide study in Finland from 1953 to 1995

The aim of this study was to investigate whether patients with basal‐cell carcinoma (BCC) of the skin have an increased risk of developing other cancers. A total of 71,924 patients diagnosed with BCC between 1953 and 1995 were identified from the Finnish Cancer Registry. They were followed up for subsequent primary cancers from the date of the first BCC diagnosis to the end of 1995. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated based on national rates. Altogether 11,042 subsequent primary cancers occurred among the study cohort during 625,000 person‐years of follow‐up. Risk increases were observed for non‐melanoma skin cancer (SIR 3.79, 95% CI 3.59–4.00) and skin melanoma (SIR 2.34, 95% CI 2.08–2.61). The five other primary sites presenting the highest SIRs were salivary glands (SIR 3.30), lip (2.19), small intestine (1.85), nose (1.73) and pharynx (1.71). Patients who were less than 40 years of age at the time of BCC diagnosis had a significantly higher relative risk for a subsequent new cancer than the older patients (ratio of the SIRs 1.29, 95% CI 1.10–1.51). Time since BCC diagnosis did not materially influence the overall relative risk of subsequent cancers. Part of the increase in the risk of skin cancer is likely to be due to enhanced diagnostic activity after an initial diagnosis of BCC. However, the increases in the risk of several non‐cutaneous cancers suggest a generalized carcinogenic role of some factors in the BCC pathogenic pathways. Int. J. Cancer 87:283–288, 2000.

Stress of daily activities and risk of breast cancer: A prospective cohort study in Finland

The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast‐cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subjects own appraisal of daily stress. It was assessed in 1975 and 1981 by a self‐administered questionnaire, which also provided information on subject characteristics and other known breast‐cancer risk factors. Follow‐up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable‐adjusted HRs for breast‐cancer risk were 1.00 (reference), 1.11 (95% CI 0.78–1.57) and 0.96 (95% CI 0.53–1.73) by increasing level of stress. Neither shifting of the SDA cut‐off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self‐perceived daily stress and breast‐cancer risk.