Aage Andersen

Birth defects among offspring of Norwegian farmers, 1967-1991.

We investigated birth defects (N = 4,565) reported to the Medical Birth Registry of Norway among 192,417 births between 1967 and 1991 to parents identified as farmers in five agricultural and horticultural censuses between 1969 and 1989. The prevalences at birth of all and specific birth defects deviated little from those among 61,351 births to non‐farmers in agricultural municipalities. We classified exposure indicators on the basis of information provided at the agricultural censuses. The main hypotheses were that parental exposure to pesticides was associated with defects of the central nervous system, orofacial clefts, some male genital defects, and limb reduction defects. We found moderate increases in risk for spina bifida and hydrocephaly, the associations being strongest for exposure to pesticides in orchards or greenhouses [spina bifida: 5 exposed cases, odds ratio (OR) = 2.76, 95% confidence interval (CI) = 1.07–7.13; hydrocephaly: 5 exposed cases, OR = 3.49, 95% CI = 1.34–9.09]. Exposure to pesticides, in particular in grain farming, was also associated with limb reduction defects (OR = 2.50; 95% CI = 1.06–5.90). We also saw an association with pesticides for cryptorchism and hypospadias. We found less striking associations for other specific defects and pesticide indicators, animal farming, and fertilizer regimens.

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population‐based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943–2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24–1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non‐melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.

Smokeless tobacco use and risk of cancer of the pancreas and other organs

Limited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco‐specific N‐nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas.

Mortality among workers employed in the titanium dioxide production industry in Europe

AbstractObjectives: To assess the risk of lung cancer mortality related to occupational exposure to titanium dioxide (TiO2). Methods: A mortality follow-up study of 15,017 workers (14,331 men) employed in 11 factories producing TiO2 in Europe. Exposure to TiO2 dust was reconstructed for each occupational title; exposure estimates were linked with the occupational history. Observed mortality was compared with national rates, and internal comparisons were based on multivariate Cox regression analysis. Results: The cohort contributed 371,067 person-years of observation (3.3% were lost to follow-up and 0.7% emigrated). 2652 cohort members died during the follow-up, yielding standardized mortality ratios (SMRs) of 0.87 (95% confidence interval [CI] 0.83–0.90) among men and 0.58 (95% CI 0.40–0.82) among women. Among men, the SMR of lung cancer was significantly increased (1.23, 95% CI 1.10–1.38); however, mortality from lung cancer did not increase with duration of employment or estimated cumulative exposure to TiO2 dust. Data on smoking were available for over one third of cohort members. In three countries, the prevalence of smokers was higher among cohort members compared to the national populations. Conclusions: The results of the study do not suggest a carcinogenic effect of TiO2 dust on the human lung.

The role of alcohol, tobacco, and dietary factors in upper aerogastric tract cancers: a prospective study of 10,900 Norwegian men.

Previous knowledge on risk factors for oral, pharyngeal, laryngeal, and esophageal cancer has been based mainly on case-control studies. In the present study, the impact of alcohol consumption, tobacco smoking, and dietary factors on upper aerogastric tract cancer risk was studied in a cohort of 10,960 Norwegian men followed from 1968 through 1992, in which period a total of 71 upper aerogastric tract cancers occurred. The relative risk (RR) of cancer was 3.9 (95 percent confidence interval [CI] = 2.1-7.1) for the highest consumption group of alcohol and 4.7 (CI = 1.7-13.2) for the highest smoking level, compared with the respective reference groups. Among the dietary items, high consumption of oranges was associated with reduced cancer risk (RR = 0.5, CI = 0.3-1.0), as was high consumption of bread (RR = 0.2, CI = 0.1-0.5). Frequent consumption of beef and bacon increased relative cancer risk bordering on significance. The present results are largely in accordance with previous studies. The decreased risk associated with a high intake of bread deserves further investigation.

Risk of breast cancer among Norwegian women with visual impairment.

Experimental studies suggest that melatonin has a protective effect against breast cancer. Exposure to light suppresses melatonin secretion, but to a lesser degree in totally blind persons. Breast cancer was investigated in a cohort of 15 412 Norwegian visually impaired women. The risk among totally blind women was 0.64 (95% CI = 0.21–1.49, 5 cases only), and for those who became blind before age of 65, the SIR was 0.51 (95% CI = 0.11–1.49). Our findings give support to the ‘melatonin hypothesis’.

Long-term changes in adult asthma prevalence

There has been an increase in asthma prevalence among children. Little evidence is available regarding long-term changes in asthma prevalence in adults. Two cross-sectional studies were performed among adults aged 15–70 yrs in Oslo, Norway, in 1972 and again in 1998–1999 (n=39,998). A postal self-completed questionnaire was used. Exactly the same questions and survey methods were used in both studies. In 1998–1999, additional telephone follow-up was included for postal nonresponders. The crude prevalence of ever having had a doctors diagnosis of asthma increased from 3.4 to 9.3%. The prevalence of wheezing increased from 17.8 to 25.8% and attacks of breathlessness from 12.6 to 16.7%. After controlling for smoking, the risk of asthma among those aged <40 yrs had tripled. The increase in asthma was 50% greater in females than males. The prevalence of symptoms increased less than asthma diagnosis. Wheezing increased by 50% in those aged <40 yrs, with smaller increases at greater ages. The increase in symptoms was seen among both asthmatics and nonasthmatics. There has been a large increase in the prevalence of asthma diagnosis and asthma-like symptoms in adults. The increase is less pronounced among those aged >40 yrs.

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80–3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Nordic biological specimen banks as basis for studies of cancer causes and control - More than 2 million sample donors, 25 million person years and 100 000 prospective cancers

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at −20°C to −135°C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkins lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43–51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkins lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkins lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkins lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.