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Objective: To study associations between established risk factors for pre-eclampsia and different clinical manifestations of the disease., Design: A population-based, nested case-control study., Setting: Information from 12,804 consecutive deliveries that took place over three years at a birth clinic, which alone serves a population of nearly 240,000 in Rogaland county, Norway., Subjects: Cases of pre-eclampsia (n = 323) and healthy controls (n = 650) were selected. Pre-eclampsia was defined as increase in diastolic blood pressure (> or = 25 mmHg to > or = 90 mmHg) and proteinuria (> or = 1+ by dipstick testing) after 20 weeks of pregnancy., Main Study Measures: Parity, previous pre-eclampsia, blood pressure, maternal weight, and maternal smoking were included as study variables. Women with pre-eclampsia were grouped according to clinical manifestations of the disease (i.e. severity [mild, moderate or severe]) and time of onset (early or late gestation). Associations with the study factors were estimated as relative risks (odds ratio, OR)., Results: Both nulliparity and hypertension increased pre-eclampsia risk, with no clear preference for any clinical subtype. High maternal weight was related to a higher risk of mild and moderate, but not severe, pre-eclampsia. Previous pre-eclampsia strongly increased the risk for pre-eclampsia in the current pregnancy, and the risk of early onset disease was especially high (OR 42.4; 95% CI 11.9-151.6). Overall, smoking was associated with a reduced risk for pre-eclampsia (OR 0.6; 95% CI 0.4-0.9). However, no effect of smoking was observed in the early onset disease group and among women with repeated pre-eclampsia., Conclusion: Nulliparity and hypertension increased the risk for each subgroup of pre-eclampsia, but high maternal weight, previous pre-eclampsia and smoking were not consistently associated with each clinical subtype. This observation may suggest that heterogeneous clinical manifestations of pre-eclampsia may be preceded by different pathological mechanisms.

Objectives: Cancer of the pancreas is highly fatal and, despite extensive scrutiny, only cigarette smoking stands out as a likely causal agent in epidemiological studies. To explore to what extent different lifestyle factors are associated with the risk of pancreatic cancer, data from a large health screening survey in a county in Norway were analyzed., Methods: Our study included 31,000 men and 32,374 women initially free from any diagnosed cancer, and during 12 years of follow-up, 166 incident cases of pancreatic cancer were diagnosed at the Cancer Registry., Results: Compared with never smokers, we found a two-fold increased risk among current smokers, and a dose-response association with number of cigarettes (p for trend = 0.02 for both men and women) and with number of pack-years (p for trend = 0.02 for men and 0.01 for women). The risk among former smokers quitting more than 5 years before study entry was close to the risk of never smokers. Compared with persons who reported never or infrequently to be physically worn out after a day's work, the relative risk (RR) among those who nearly always became worn out was 2.9 (95% confidence interval (CI) = 1.4-5.8) for men and 3.8 (95% CI = 1.6-9.2) for women. Divorced or separated men had a risk of 3.1 (95% CI = 1.3-7.2) compared with married men. We observed a higher risk among women in occupations of high socioeconomic status (RR = 2.5; 95% CI = 1.2-5.2), and among men occupied in farming, agriculture or forestry (RR = 2.1; 95% CI = 1.1-4.0), compared with persons in occupations of low socioeconomic status., Conclusions: Our results confirm the findings of previous studies that indicate a causal role of cigarette smoking in pancreatic cancer. Moreover, we found that the risk of former smokers may approach the risk of never smokers within a few years subsequent to quitting.

Objective: To evaluate the possible benefits of the routine use of ultrasound screening in pregnancy., Design: A randomized controlled trial was designed to detect a 50% difference in the incidence of induction for apparent post-term pregnancies between women who were screened with ultrasound and unscreened women. A total of 1628 pregnant women from the general population were included. Eight hundred and twenty-five were allocated to an ultrasound examination at the 18th and 32nd week of pregnancy in addition to receiving routine antenatal care. The remaining 803 women received standard antenatal care, but could only be referred for ultrasound examination on clinical indication., Results: The incidence of induced labor due to apparent post-term pregnancies was approximately 70% lower in the ultrasound-screened group. Inductions from all causes were also less frequent among ultrasound-screened women. There were six perinatal deaths among the screened and seven among the controls after excluding three lethal malformations among the controls. There was no difference in Apgar score after 1 min, but the proportion with Apgar score less than 8 after 5 min was lower among the screened group (P = 0.04). The need for positive pressure ventilation for more than 1 min was lower among the screened group (P = 0.02). Birth weight was slightly higher in the screened group (39 g), but the difference was not statistically significant. Among the controls three pairs of twins remained undiagnosed until the mothers were admitted to the hospital in labor at between 36 and 38 weeks gestation., Conclusion: These results suggest that for women who were screened with ultrasound, obstetricians were less likely to induce labor due to apparent post-term pregnancy, than for women who were not screened. All 10 pairs of twins in the screened group were diagnosed at the routine examination. These data also suggest that perinatal morbidity might be slightly lower in the screened group.

International and interethnic differences in prostate cancer incidence suggest an environmental aetiology, and lifestyle and socio-economic factors have been studied, but with divergent results. Information on a cohort of 22,895 Norwegian men aged 40 years and more was obtained from a health examination and two self-administered questionnaires. Information on incident cases of prostate cancer was made available from the Cancer Registry. We used the Cox proportional hazards model to calculate incidence rate ratios as estimates of the relative risk (RR) with 95% confidence interval (CI). Reported P-values are two-sided. During a mean follow-up of 9.3 years, 644 cases were diagnosed. Risk was elevated among men in occupations of high compared to low socio-economic status (RR = 1.30; 95% CI 1.05-1.61), and among men with high education compared to the least educated (RR = 1.56; 95% CI 1.11-2.19). A RR of 1.56 (95% CI 0.97-2.44) suggests a higher risk among divorced or separated men, compared with married men. We also found indications of a weak negative association with leisure-time physical activity (RR = 0.80; 95% CI 0.62-1.03 for high vs low activity), a weak positive association with increasing number of cigarettes (P = 0.046), while alcohol consumption was not related to the risk of prostate cancer. These results show that high socio-economic status is associated with increased risk of prostate cancer, and that divorced or separated men might be at higher risk than married men. Data from this study also indicate that high levels of physical activity may reduce prostate cancer risk.

Objectives: Few risk factors for prostate cancer are known, but both endocrine changes and dietary factors have been implicated in the etiology of the disease. Anthropometry may therefore provide a tool in the search for carcinogenic mechanisms connected to these suggested causal components., Methods: We have studied the association between body size and prostate cancer risk in a prospective study of 22,248 Norwegian men. During 12 years of follow-up, 642 men developed cancer of the prostate. A possible association between anthropometry (height, weight, body mass index (BMI), and lean body mass (LBM)) and prostate cancer risk was assessed using Cox regression analysis., Results: Overall, we observed no significant trend for any of the variables studied, although an excess risk of prostate cancer with increasing height was suggested by an age-adjusted relative risk of 1.2 (95% CI = 0.9-1.6) for the tallest compared to the shortest quintile of men. None of the other three variables (weight, BMI, and LBM) displayed any consistent relation with the risk of prostate cancer., Conclusions: We conclude that these results do not indicate a strong association between anthropometric factors and risk of prostate cancer.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

A smoking intervention counseling program was applied among asbestos-exposed male smokers younger than 65 years of age to examine the effect of an intervention based on risk communication. Intervention subjects (n = 431) were invited to a health status checkup combined with physician-delivered smoking intervention counseling. Control subjects (n = 141) received no intervention. After 1 year, 5% of the responders in the intervention group, versus 3.4% in the control group, had stopped smoking. Corresponding conservative estimates were 3.5% and 2.6%, respectively. The quitters had been exposed to a higher "dose" of asbestos but had smoked less, and for a shorter period, than had the continuing smokers. Counseling by a general physician increased successful quitting threefold, compared to counseling by a physician in a specialized institution. These results suggest a potential for smoking cessation among subjects at high risk of lung cancer due to asbestos exposure. General practice care may be an appropriate setting both for identification of such subjects and for intervention.

First, we studied the relative risk of cancer among women born between 1935 and 1954 who had experienced a child's death, compared with women without this experience. Second, we examined whether survival was any different between cancer patients in the 2 groups. The study was a population-based nested case-control study that included 14,669 cancer cases and 29,750 age-matched controls. The women who were included as incident cases were further analyzed using Cox regression in a study of total survival. The overall relative risk of cancer among women who had lost a child was nearly identical to that of women who had not lost a child (OR = 0.96, 95% confidence interval 0.87-1.07), after adjustment for age and parity. In the analysis of specific cancer sites, there was no difference in relative risk between the 2 groups. In relation to cancer survival, we found that patients who had lost a child had an overall risk of dying that was nearly identical to patients who had not had this experience (HR = 1.08, 95% confidence interval 0.92-1.26), after adjustment for age and stage at diagnosis. For specific sites of cancer, the results also showed no difference in survival between the 2 groups. In conclusion, risk and survival of cancer were not different among women who had experienced the death of a child from the risk and survival among women without this experience.

The purpose of this study was to examine respiratory symptoms and lung function (forced vital capacity [FVC] and forced expiratory volume in 1 second [FEV1]) as related to changes in smoking habits in subjects previously exposed to asbestos. The study was linked to a smoke-ending program among asbestos-exposed males. Subjects were recruited from a population-based survey, and 231 smokers met for the baseline consultation. The baseline prevalences of cough, chronic cough, and dyspnea among smokers were 68.0%, 44.6%, and 42.4%, respectively. Both smoke-ending (n = 10) and tobacco reduction (n = 52) during the 2-year follow-up resulted in remission of cough and chronic cough, whereas dyspnea was unaffected. When the 2-year measurements of FVC and FEV1 were adjusted for the respective baseline measurements, FEV1 tended to improve in subjects who had quit during the study, relative to the continuing smokers. It was concluded that both smoke-ending and reduction of tobacco consumption resulted in reduction of cough and chronic cough, but not of dyspnea. The study further suggests a possible positive effect of smoking cessation on FEV1, but not merely by reduction of tobacco consumption.

Study Objective: The difference in risk of cancer between never married women and married women in their first marriage and whether survival from cancer was any different between the two groups were studied., Design: This was a population based, nested case-control study of cancer in Norwegian women diagnosed between 1966 and 1990, and followed up with regard to overall survival until the end of 1991., Setting: Norway., Participants: These were Norwegian women born between 1935 and 1954. The case-control study included 12,237 married and 1466 unmarried cases, and 26,075 married and 2768 unmarried controls. In the survival analysis, 11,943 married and 1473 unmarried cases were included., Main Results: Unmarried women had an overall increased cancer risk (OR = 1.13, 95% CI 1.05, 1.21), which could be attributed to cancer of the ovaries, uterus, brain and haematological malignancies. For cervical and thyroid cancer, the risk was lower than for married women. In the survival analysis, unmarried cases had an overall 26% increased risk of dying (HR = 1.26, 95% CI 1.15, 1.39), after adjustment for age and stage at diagnosis. The increased death rate was seen for cancer of the cervix, lung, and thyroid., Conclusions: Since most unmarried women were nulliparous, this might explain their increased risk of ovarian and uterine cancer. The increased risk of brain tumours and haematological malignancies may result from selection bias, since disease among unmarried women may cause a large proportion to remain unmarried. The lower survival in unmarried cases may support the hypothesis that psychosocial factors play a role in the prognosis of cancer patients.

Several lines of evidence suggest that a number of immunoactive cytokines participate in early reproductive events such as implantation and placental development. Furthermore, cytokines may influence embryo growth and differentiation. In the present study, the production of tumour necrosis factor (TNF), interleukin-1 (IL1), interleukin-6 (IL6) and transforming growth factor-beta (TGF beta) during the first 48 h after oocyte retrieval during in-vitro fertilization was investigated. In addition, the question was raised whether soluble receptors may contribute to cytokine activity regulation in early reproduction, and concentrations of TNF and IL6 receptors in culture media were determined. Finally, an investigation of whether any association exists between cytokine concentrations and embryo morphology was performed. Media from 256 embryos were analysed. IL1, IL6 and TGF beta were produced during the 48 h culture period, whereas no TNF was detected. Levels of IL1 and IL6 were significantly higher in media from the first 24 h culture period than from the second period, whereas TGF beta concentrations in supernatants from the two observation periods did not differ. IL6 receptors were not detected, whereas TNF receptors (p75) appeared in media from the 24-48 h culture period. Granulosa, cumulus and sperm cells are potential sources of cytokine production, especially during the first 24 h period. The contribution of the embryo to cytokine/cytokine receptor production remains an open question. No significant correlation was observed between cytokine/cytokine receptor concentrations and embryo morphological score.

Several studies have shown that low blood pressure in individuals age 65 years and older is related to increased overall mortality. We hypothesize that this association is secondary to serious underlying illness, which has caused blood pressure reduction and, subsequently, has increased the risk of dying. Our study population was comprised of individuals age 20 years and older in the county of Nord Trøndelag in Norway, who were studied in a general health survey between 1984 and 1986. We had measurements of blood pressure, blood glucose, weight, height, and other information for 9,732 women and 8,290 men age 65 years or older. During approximately 6 years of follow-up, 2,122 women and 2,578 men died. For both genders, low systolic pressure was not associated with increased mortality, and the mortality curve did not display a J-shaped relation, after adjustment for age, marital status, body mass index, blood glucose, self-assessed health, use of antihypertensive medication, and history of diabetes and cardiovascular diseases. For diastolic pressure, however, women in the lowest category (< 75 mmHg) had an adjusted mortality rate ratio of 1.21 (95% confidence limits = 1.05, 1.39), compared with reference women (80-87 mmHg). Among men, the analogous mortality rate ratio was 1.16 (95% confidence limits = 1.02, 1.31). To reduce further the potential confounding between diastolic pressure and underlying illness, we excluded users of antihypertensive medication as well as the 2 first years of follow-up. After these procedures, the J-shaped mortality curve was not present among women, and it was substantially reduced among men. Thus, the results for both men and women indicated that the age-adjusted J-shaped relation between diastolic blood pressure and mortality was confounded with indicators of ill health, and that the often-found association between low diastolic blood pressure and increased mortality is indirect, possibly caused by serious underlying disease.

We have examined whether the risk of cancer among divorced or widowed Norwegian women born between 1935 and 1954 was any different from that of married women. Among a total of approximately 600,000 women, we applied a nested case-control design. Thus, the study was population-based and included 17,235 incident cases of cancer with 34,460 age-matched controls. For widowed women, there was no overall relation with cancer. For divorced women, 2 strikingly different associations were apparent. A reduced risk was seen for cancers of a number of sites, including thyroid, endometrium, colorectum, and breast, as well as malignant melanoma and hematologic malignancies, with statistically significant estimates of relative risk ranging from 0.64 to 0.84. In contrast, divorced women had a strongly elevated risk of lung and cervical cancer. Moreover, there was a gradual reduction in the relative risk of cancer at some sites with increasing age at divorce, and with duration of marriage prior to divorce. In this study of middle-aged women, the risk of cancer among widows was no different from that of married women. Divorced women had an increased risk of cancers which are related to cigarette smoking but, simultaneously, a reduced risk of cancer at a number of other sites. Since the negative associations for some cancers were strongly related to increasing age at divorce and to duration of marriage, the results may indicate that the reduction in risk is related to factors which characterize the marital period preceding divorce.

The purpose of this paper is to examine a possible association between prenatal ultrasonography and delayed speech among children. A follow-up study was carried out on primary school children born to women who took part in two randomized controlled trials of routine ultrasonography during pregnancy. Of 2428 eligible singletons, 2161 (89%) were followed up with a parental questionnaire and with information from maternal and child health centers. Parents assessed the development of speech during the childhood years and reported their observations in a questionnaire. Maternal and child health center records provided data on the children's development of speech and any referrals of children to a speech therapist. No significant differences between ultrasound-screened children and their controls were found in the parental assessment of speech development. According to health center records, screened children were less likely to be referred to a speech therapist (odds ratio, 0.51; 95% confidence interval 0.31, 0.85), but there were no other significant differences in speech development as reported in the health center records. We conclude that routine ultrasonography in utero is not associated with delayed speech in children., (Copyright 1994 International Society of Ultrasound in Obstetrics and Gynecology)

Reduction in the incidence of competing diseases will steadily increase the relative importance of cancer as a cause of death. A curative break-through has occurred for some, but definitive solutions in the treatment of a majority of cancers remain undiscovered. Attempts at primary and secondary prevention have been encouraging in some areas, but progress is slow, and suggests that the search for causes of cancer should be intensified. It has been estimated that between 30% and 60% of all cancers may be attributable to dietary factors. The main hypothesis has suggested that intake of animal fat increases the risk. This hypothesis has been extensively tested, especially in relation to cancer of the breast and colon, and ecological studies, which have correlated use of dietary fat with incidence or mortality between countries, have confirmed the hypothesis. For cancer of the colon, it has also been verified in case-control and cohort studies, but analytical epidemiological studies have failed to show a consistent positive association between dietary fat and risk of breast cancer. Simultaneously, dietary factors with protective potential have received increasing attention. An overview of all studies which have investigated the relation between dietary fruit and vegetables and the risk of cancer showed a highly consistent protective effect, indicating that fruit and vegetables may provide general protection against cancer. Maybe the search for a "magic" protective factor is blocking this already documented insight, which suggests that daily intake of five servings of fruits or vegetables may have a strong and consistent protective effect on risk of cancer.

Epidemiological studies have suggested that moderate intake (1-2 drinks per day) of alcohol may increase the risk of breast cancer by more than 50%. A relatively large proportion of women in many countries consume alcohol at this level, and a precise assessment of the related breast cancer risk is therefore important. In this paper we have reviewed all published studies subsequent to a comprehensive meta-analysis on alcohol and breast cancer, published in 1988. Among four cohort studies, the relative risk of breast cancer associated with 1-2 drinks per day (compared with no drinking) varied between 1.0 and 1.3, and the null value of 1.0 was included in the 95% confidence interval for each of the studies. For consumption higher than two drinks per day, two of the four cohort studies indicated a significantly increased risk. Among 14 case-control studies, the point estimates showed increased breast cancer risk in 11, and five were statistically significant. Three studies indicated a negative association, but the confidence interval included 1.0 in two of them. Among case-control studies which provided information on intakes higher than two drinks, eight out of 13 studies showed a statistically significant positive association. Collectively these studies support a weak positive association between moderate consumption of alcohol and breast cancer risk. The tendency between studies is consistent, but the precision of the estimate of relative risk is low in most studies. Unless consumption is two drinks or higher per day, no recommendation to reduce drinking should be made based on the present evidence relating alcohol consumption to breast cancer risk.

A topic of general interest is whether important life changes may play a role in the onset of cancer. The hypothesis of this study was that death of a husband or marital divorce, is associated with an increased risk of breast cancer. The study included 4491 incident breast cancer cases and 44,910 controls, matched on age, in a population-based nested case-control study, among Norwegian women born between 1935 and 1954. The risk of breast cancer among widowed compared to married women showed an odds ratio (OR) of 1.13 [95% confidence interval (CI) 0.94-1.36], after adjusting for age at first birth and parity. For divorced women the analogous OR was 0.83 (95% CI 0.75-0.92), after adjusting for age at first birth, parity and place of residence. Thus, the results did not show any clear evidence that death of a husband or marital divorce was associated with an increased risk of breast cancer.

Earlier onset of menarche and tallness in adult women are mainly confirmed as risk markers for breast cancer. Recent disparate case-control studies have reported abdominal-type obesity and higher circulating levels of insulin, testosterone and insulin-like growth factor 1, to be further risk markers for breast cancer. There is evidence that abdominal-type obesity is recognisable in girls even before puberty, and disparate studies have shown it to be correlated with earlier onset of menarche, insulin resistance leading to hyperinsulinaemia, and an abnormal sex steroid profile. The implications are that earlier onset of puberty in a subset of girls can lead to more prolonged exposure of developing breast tissue to an abnormal sex steroid profile and also to a higher circulating level of insulin. It is postulated that these metabolic/endocrine concomitants of abdominal-type obesity could play a role in promoting mammary carcinogenesis at a young age, particularly if genetic predisposition is present.

We have tested the hypothesis that specific polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families, as measured in serum phospholipids, are negatively associated with the risk of breast cancer. The study is based on serum samples from women who have donated blood to the Janus serum bank at the University Hospital in Oslo, Norway. It consists of sera from 87 women who developed breast cancer (cases) subsequent to blood donation and 235 women who were free of any diagnosed cancer (controls), but were of similar age and had similar blood storage time as the cases. We measured fatty acids (monounsaturated, polyunsaturated and saturated) in serum phospholipids, and made comparisons between cases and controls. The results showed that there was an inverse relation between the n-6 PUFA linoleic acid (18:2n-6) and risk of breast cancer, but this association was restricted to women who were 55 years and younger. In this age group, the relative risk (odds ratio) of women in the highest quartile of linoleic acid was 0.4 (95% confidence limits, 0.2 and 1.0) compared with women in the lowest quartile, and there was a negative trend over quartiles of linoleic acid (Mantel's chi for trend = -2.49, P < 0.02). No association was noted between the n-3 PUFA of marine oil origin and breast cancer risk. If the measured concentration of linoleic acid in serum phospholipids reliably reflects dietary intake, these data suggest that linoleic acid in the diet may decrease breast cancer risk among women at premenopausal and perimenopausal age. No similar association with n-3 unsaturated fatty acids was observed. It is noteworthy that none of the measured fatty acids (saturated or unsaturated) showed a positive association with breast cancer risk.

The study was performed to investigate any associations between routine ultrasonography during pregnancy and subsequent growth during childhood. A follow-up was carried out of children born to women who took part in two randomized, controlled trials of ultrasonic screening during pregnancy. From a total of 2428 eligible children, 2140 (88%) were followed up with measurements of growth at Norwegian maternal and child health centers. The body weight and height were recorded at birth and at 3, 6 and 12 months of age; and subsequently at 2, 4 and 7 years of age. A repeated-measures analysis of growth was carried out, stratified by maternal smoking in a subsample of 1201 children. No significant differences between ultrasound-screened children, and their controls, were found in mean body weight, or height, at birth and at all the subsequent visits to the health centers. However, the repeated-measures analysis of variance in the subsample indicated that growth from birth to 7 years of age differed significantly (p = 0.02) between screened and control children of mothers who reported smoking at the first antenatal visit. We conclude that children who were routinely exposed to ultrasonography in utero showed no statistically significant differences in growth during childhood compared to control children., (Copyright 1993 International Society of Ultrasound in Obstetrics and Gynecology)

The study was performed to investigate any associations between routine ultrasonography during pregnancy and subsequent reduced vision and/or hearing among children. A follow-up was carried out of primary school children born to women who took part in two randomized, controlled trials of routine ultrasonography during pregnancy. Of 2428 eligible singletons, 2161 (89%) were followed up with a parental questionnaire and with information from maternal and child health centers. Parents assessed vision and hearing in their children and reported their observations in questionnaires. At the age of 7 years, the children were also screened with bilateral visual acuity tests and pure tone audiometry at public maternal and child health centers. No significant differences between ultrasound-screened children and their controls were found in the parental assessment of vision or hearing. The objective tests did not show any significant differences between children in the two groups with regard to visual acuity or hearing. The risk of reduced vision or hearing was no greater for children of mothers who had been offered routine ultrasonography during pregnancy than for those whose mothers had not received that offer., (Copyright 1992 International Society of Ultrasound in Obstetrics and Gynecology)

Over a five-year period of registration in the county of Sør-Trøndelag we studied whether the frequency of consulting for one of three major psychiatric diagnostic groups (psychosis, neurosis, or "other") depended on the type of municipality (rural, coastal, urban) where the patient was resident. Diagnoses were based on consultations with a staff member of the regional outpatient psychiatric clinic, and the underlying population was described in the National Census, 1980. The results showed that, in general, urban residents sought help more frequently from the psychiatric outpatient clinic than rural residents did, (relative risk = 1.6, 95% confidence interval 1.4 to 1.8). The increased "risk" was attributed to a relatively larger number of neuroses and "other" diagnoses in the urban areas. The risk of consulting for psychosis was higher among coastal residents (relative risk = 1.8, 95% confidence interval 1.4 to 2.3) than among rural residents, was particularly evident among coastal residents between 16 and 39 years of age (relative risk = 4.1, 95% confidence interval 2.1 to 8.5), and was equally strong for men as for women. This study confirms that, in general, the risk of seeking outpatient psychiatric treatment is higher among urban than among rural and coastal residents. The apparently higher frequency of requests to the outpatient clinic for help for psychosis among coastal residents should be balanced against the tendency for city residents with psychosis to be admitted directly to the psychiatric hospital.

It has been suggested that pregnancy is associated with a short-term increased risk of breast cancer followed by a life-long protection. We studied 340 incident cases of breast cancer in relation to parity, age at first full term birth, and time since last child birth during 14 years follow-up in a prospective cohort of 29,981 Norwegian women. We found no evidence for a transient increase in risk of breast cancer subsequent to pregnancy followed by a reduction in risk of long lasting duration. However, our results indicate that up to an approximate age of 45 years, the nulliparous have a lower breast cancer risk than everparous women. Among parous women, there was an increasingly protective effect on breast cancer risk at a young age (less than 50 years) with increasing number of child births, independent of age at first birth, whereas the protection associated with an early age at first full term pregnancy may increase in importance with increasing age. This finding may reconcile conflicting reports related to these two factors. This study confirms the results of previous investigations suggesting that a "cross-over" in breast cancer incidence between nulliparous and ever-parous women appears to take place some time during the fifth decade of life.

The nutritional component during childhood and adolescence that contributes to variation in adult height may be associated with the subsequent risk of breast cancer in women. Municipalities in three Norwegian counties were ranked and divided in three categories according to resident women's height, where variation in height is assumed to reflect variation in nutritional living conditions during childhood and adolescence. For each county observed number of incident cases (1975-1984) and deaths (1966-1987) of breast cancer in "short", "medium" and "tall" municipalities were compared with the expected number computed from the national rates. An analogous analysis was done, comparing incidence and mortality between 18 Norwegian counties, but using county-specific infant mortality for the period 1921-1935 as an alternative indicator of living conditions. There was a consistent positive association between height in municipalities and breast cancer incidence (overall P trend = 0.02) and mortality (overall P trend = 0.05). For infant mortality between counties, there was no association with breast cancer. In populations where variation in height reflects variation in nutritional living conditions during childhood and adolescence, there may be a positive association between height and risk and mortality of breast cancer.

The associations of breast cancer risk with height and body mass index have been examined in 291 cases of breast cancer that occurred among 25,967 Norwegian women during a mean follow-up of approximately 14 years (range 12-16 years). There was an overall increased risk of breast cancer with increasing body height, and the relative risk of women in the fourth quartile of height (mean = 170 cm) was 1.43 (95% confidence limits, 1.18-1.73) compared to women in the lowest quartile (mean = 155 cm), after adjusting for age, parity, age at first birth, and county of residence. Simultaneously, there was an overall inverse relation between body mass index (BMI) and breast cancer risk, which, however, was confined to women 50 years or younger. After adjustment for age, parity, age at first birth, and county of residence, the relative risk of women (less than or equal to 50 years) in the highest quartile of BMI (mean Quetelet = 30) was 0.63 (95% confidence limits, 0.48-0.82), compared to women in the lowest (mean Quetelet = 21). We propose that the lower breast cancer risk in shorter women may reflect caloric restriction during the pre- and peripubertal period, which may affect hyperplastic growth, and lead to a reduced number of breast tissue cells. The negative association with BMI may be related to a lower rate of cell division of breast tissue among obese premenopausal women.

More than six-fold variation in incidence between countries, an increasing incidence among immigrants to high incidence areas, and a general increase in the incidence of breast cancer within countries, are factors which suggest a potential for prevention. Reproductive factors such as early menarche, late age at first full term birth, nulliparity, and late age at menopause increase risk of breast cancer, but manipulation of any one of these factors does not seem to be a realistic preventive tool. Nevertheless, the future possibility of using tamoxifen as a chemopreventive agent against breast cancer is discussed, particularly in relation to women at increased risk due to familial clustering. Alcohol consumption by young women, and overweight among postmenopausal women may also increase the incidence of breast cancer. Consequently, reduced alcohol intake by young women, and weight reduction among overweight women after menopause may reduce the risk of breast cancer.

Mean overall 5-year survival related to preclinically determined total serum cholesterol, body mass index (BMI), height and cigarette smoking has been analysed among 242 incident cases of breast cancer aged 36-63 years that developed in a population of 24,329 Norwegian women during a mean follow-up of 12 years (range 11-14). The study factors were ascertained at least 1 year prior to diagnosis (mean = 8 years), and the cases have been followed up with respect to death for a mean time of approximately 5 years after diagnosis. Patients whose preclinical total serum cholesterol values were within the highest quartile (greater than or equal to 7.52 mmol/l, mean = 8.58 mmol/l) of the underlying population had a hazard ratio of dying of 2.0 (95% confidence limits, 1.1 and 3.7) compared to cases with cholesterol values in the lowest quartile (mean = 5.28 mmol/l), after adjustment for age at diagnosis, clinical stage, and body mass index. In relation to BMI (Quetelet's index: weight/height2) patients who were obese prior to diagnosis were at higher risk of dying than those who were lean. Compared to patients in the lowest quartile of BMI (mean Quetelet = 21), the hazard ratio was 2.1 (95% confidence limits, 1.2 and 3.8) for patients in the highest quartile (mean Quetelet = 30), after adjustment for age at diagnosis, clinical stage, and total serum cholesterol. For height and for cigarette smoking, no relation with survival was observed. A potential problem of this study might be insufficient information about other well known prognostic factors, but the results suggest that preclinical total serum cholesterol and BMI are positively associated with the risk of dying among women who develop breast cancer.

The association between the frequency of meat and fish intake and the incidence rate of breast cancer has been analyzed in 152 incident cases that developed among 14,500 Norwegian women during 11 to 14 years of follow-up. At the time of dietary inquiry they were between 35 and 51 years of age. A positive association was observed between the frequency of overall meat intake and breast cancer risk. There was an age-adjusted incidence rate ratio (IRR) of 1.8 (95% confidence limits, 1.1 and 3.1) for women who had a main meal with meat 5 times or more per week compared to women who had 2 meat dinners or less per week, and this association displayed a linear trend (chi 2 trend = 4.30, p = 0.04). No association was detected between the overall frequency of fish for dinner and breast cancer risk (chi 2 trend = 1.39, p = 0.24), but there was an inverse relation with the frequency of main meals containing fish in poached form. The age-adjusted IRR was 0.7 (95% confidence limits, 0.4 and 1.0) for women who had poached fish for dinner at least 5 times per month compared to women who had fish in this form twice monthly or less often (chi 2 trend = 3.56, p = 0.06). The positive association with meat may be in accordance with the hypothesis that dietary fat increases the risk of breast cancer. Although there was no association with overall fish intake, the inverse relation with poached fish might deserve further investigation.

The association between total serum cholesterol and triglycerides and the incidence rate of breast cancer has been examined in 242 incident cases of breast cancer that developed among 24,329 Norwegian women during 11-14 years of follow-up. At the time of lipid measurement they were between 35 and 51 years of age. There was an inverse relation between serum cholesterol and risk of breast cancer which was confined to women diagnosed before the age of 51. The incidence rate ratio was 0.53 (95% confidence limits, 0.32 and 0.88) for women in the highest quartile of serum cholesterol (mean = 8.52 mM = 329 mg/100 ml) compared to women in the lowest quartile (mean = 5.28 mM = 204 mg/100 ml), and the relation displayed a negative trend over quartiles of cholesterol (chi 2 for trend = 3.94, P = 0.05). No association with cholesterol was found among cases diagnosed during the initial 2 years of follow-up, whereas a strong inverse relation was observed among cases that were diagnosed during the following 4 years (chi 2 trend = 12.6, P less than 0.001). For serum triglycerides there was an overall negative, but not statistically significant, association with breast cancer incidence, which was weakened after further adjustment for body mass index and serum cholesterol. The lack of information on reproductive factors associated with breast cancer risk is a limitation of this study, since potential confounding with the results cannot be excluded. We conclude that there is an inverse relation between serum cholesterol and breast cancer risk among women diagnosed before the age of 51 years. The findings indicate that the negative association cannot easily be attributed to a preclinical effect of the cancer.

The association between body mass index (BMI) and the incidence rate of breast cancer has been examined in 236 cases of breast cancer that developed among 23,826 Norwegian women during 11 to 14 years of follow-up. At the time of height and weight measurement they were 35 to 51 years of age, and at the end of follow-up their age was between 46 and 63 years. There was an overall age-adjusted incidence rate ratio (IRR) of 0.52 (95% confidence limits, 0.34 and 0.77) for women in the highest quartile of BMI compared to women in the lowest quartile, which was confined to an effect observed among women who were diagnosed at age 50 or earlier (IRR = 0.36). The association with BMI displayed an inverse dose-related trend (chi 2 for trend = 14.22, p less than 0.001). The negative trend was particularly pronounced among non-smoking women (chi 2 = 14.63), and no clear trend associate with BMI was observed among women who smoked 10 or more cigarettes per day (chi 2 = 0.41), indicating an interaction between BMI and cigarette smoking (chi 2 interaction = 3.86, p = 0.05). We thus suggest that there is a negative association between body mass index and risk of breast cancer among premenopausal women.

The association between cigarette smoking and incidence of breast cancer has been analyzed in 242 cases of breast cancer that developed among 24,329 Norwegian women over 11-14 years of follow-up. At baseline they were aged 35-51. There was no overall association between cigarette smoking and the risk of breast cancer. The age-adjusted incidence rate ratio (IRR) was unity (IRR = 1.04, 95% CI 0.76-1.42) for regular smokers (10 or more cigarettes daily) compared with non-smoking women. In women who reported smoking between 1 and 9 cigarettes per day there was an age-adjusted IRR of 1.28 (95% CI 0.95-1.73). The lack of association with cigarette smoking was replicated in subgroup analyses of women diagnosed before age 51 ("premenopausal") and among women diagnosed after this age ("postmenopausal"). However, there was a significant interaction between cigarette smoking, body mass index and age at diagnosis (P = 0.01), which might indicate that an interaction between cigarette smoking and body mass exerts differential effects on breast cancer risk in premenopausal and postmenopausal women.

Incidence density ratios of first admission to an out-patient psychiatric clinic during a 5-year (1980-84) follow-up have been studied, the exposure of interest being marital status. The measured co-variates were sex, age and residence. A nearly 4-fold excess rate ratio of admission (age adjusted IDR = 3.8, 95% c.i. 3.3, 4.4) was detected for separated/divorced versus married persons, and an 80% excess rate ratio (aIDR = 1.8, 95% c.i. 1.6, 2.0) for unmarried. The aIDR for widowed persons approximated unity. Sex and residence modified the measures of effect. Men's aIDR was consistently above that of women for all categories of marital status: unmarried men's aIDR was 2.0 versus women's 1.6; widower's 1.8 versus widows' 0.9, and the aIDR of separated/divorced men was 4.0, versus 3.6 in women. In men, residence also modified the effect in the widowed and the separated/divorced. Rural widowers experience an excess rate ratio of 2.5, versus aIDRs of 1.5 and 1.0 in the urban and the coastal. The age-adjusted IDR in separated/divorced rural men was 10.4, versus 3.9 and 0.8 in urban and coastal men. The modification caused by gender has previously been observed, and has often been explained in terms of social support and networks. The residential effect needs to be explored further.