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We measured the intercondylar notch of the femur in female handball players from radiographs of 20 players with previous unilateral anterior cruciate ligament injury, and 26 controls without injury. The groups were comparable regarding age, height, weight and level of performance. Intercondylar fossa radiographs were obtained in a posteroanterior axial position. The anterior opening of the intercondylar notch was narrower in the healthy knee of the injured group compared to the controls. There was an increased risk of anterior cruciate ligament injury associated with decreasing notch opening: female handball players with 17 mm or less anterior notch width were 6 times more susceptible to anterior cruciate ligament injury compared to players with wider notch width.

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.

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.

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.

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.

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 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.

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.

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 coffee consumption and the incidence rate of breast cancer has been analysed in 152 incident cases of breast cancer that developed among 14,593 Norwegian women during a mean follow-up of 12 years. At the time of inquiry they were between 35 and 51 years of age, and at the end of follow-up between 46 and 63. There was an overall weak negative association between daily intake of coffee and risk of breast cancer, which was not statistically significant. However, the association with coffee varied, depending on the body mass index (BMI) of the women. In the lean (Quetelet less than 24; population mean) there was an inverse relation between coffee intake and risk of breast cancer (chi 2 trend = 5.07, P = 0.02). In this group, women who reported drinking 5 cups or more per day had an age-adjusted IRR of 0.5 (95% confidence intervals, 0.3 and 0.9) compared to women who had 2 cups or less. In women with Quetelet's index equal to or greater than 24 there was a positive relation between coffee intake and breast cancer risk (chi 2 trend = 2.33, P = 0.13), where the corresponding age-adjusted IRR was 2.1 (95% confidence intervals, 0.8 and 5.2). This interaction effect between coffee intake and BMI was statistically significant (chi 2 interaction = 10.2, 3 d.f., P = 0.02). In summary, the results of this study suggest that coffee consumption reduces the risk of breast cancer in lean women, whereas coffee might have the opposite effect in relatively obese women.

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 body height and the incidence rate of breast cancer has been examined in 236 cases of breast cancer that occurred among 23,831 Norwegian women during 11-14 years of follow-up. At the time of height measurement they were 35-51 years of age. The age-adjusted incidence rate ratio (IRR) of breast cancer was 2.03 (95% of confidence limits 1.36 and 3.01) for women taller than or equal to 167 cm (mean = 170 cm) compared to women who were less than 159 cm (mean = 155 cm). The positive association with height was stronger among women who were diagnosed before the age of 51 (IRR = 2.63; 95% confidence limits 1.48 and 4.68), than among women diagnosed after this age. Moreover, the association appeared to be confined to women who had lived through their peripubertal growth during a period (1940-45) of nationally increased nutritional variability with reduction in dietary fat and restricted caloric intake. Among women born between 1929 and 1936, the relation with height displayed a strong positive linear trend (chi 2 trend = 13.4, P less than 0.001), which was not present among women born between 1925 and 1928 (chi 2 trend = 0.7, P = 0.40), nor among women born in 1937 or later (chi 2 trend = 1.5, P = 0.20). We hypothesise that a time-dependent diversity in nourishment, which may be of particular importance for women in their peri-menarcheal development, may explain the different association between body height and breast cancer risk that was observed for women in different birth cohorts.

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.