Lars Janzon

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Design and feasibility

Abstract. The Malmö Diet and Cancer study is a 10‐year prospective case‐control study in 45–64‐year‐old men and women (n = 53.000) living in a city with 230000 inhabitants. One objective is to clarify whether a western diet is associated with certain forms of cancer whilst taking other life‐style factors into account. Another broad question is whether oxidative stress and the activity in DNA‐repairing systems influence the impact of diet on the development of all or certain forms of cancer. The study is also to act as a resource available for testing new hypotheses emanating from other studies.

The Malmö Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants

In order to investigate potential selection bias in population‐based cohort studies, participants (n  = 28 098) and non‐participants (n  = 40 807) in the Malmö Diet and Cancer Study (MDCS) were compared with regard to cancer incidence and mortality. MDCS participants were also compared with participants in a mailed health survey with regard to subjective health, socio‐demographic characteristics and lifestyle. Cancer incidence prior to recruitment was lower in non‐participants, Cox proportional hazards analysis yielded a relative risk (RR) with a 95% confidence interval of 0.95 (0.90–1.00), compared with participants. During recruitment, cancer incidence was higher in non‐participants, RR: 1.08 (1.01–1.17). Mortality was higher in non‐participants both during, 3.55 (3.13–4.03), and following the recruitment period, 2.21 (2.03–2.41). The proportion reporting good health was higher in the MDCS than in the mailed health survey (where 74.6% participated), but the socio‐demographic structure was similar. We conclude that mortality is higher in non‐participants than in participants during recruitment and follow‐up. It is also suggested that non‐participants may have a lower cancer incidence prior to recruitment but a higher incidence during the recruitment period.

Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: Main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS)

BackgroundStatins reduce cardiovascular events and progression of carotid intima-media thickness (IMT). &bgr;-Blockers are also known to reduce cardiovascular events, but less is known about their effects on carotid IMT. Methods and ResultsWe conducted a randomized, double-blind, placebo-controlled, single-center trial to compare the effects of low-dose metoprolol CR/XL (25 mg once daily) and fluvastatin (40 mg once daily) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease. Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables. Death and cardiovascular events were monitored. Progression of IMTmax in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL (−0.058 mm/y; 95% CI, −0.094 to −0.023;P =0.004; and −0.023 mm/y; 95% CI, −0.044 to −0.003;P =0.014, respectively). Incidence of cardiovascular events tended to be lower in metoprolol CR/XL–treated patients (5 versus 13 patients, P =0.055). Rate of IMTmean progression in the common carotid at 36 months was reduced by fluvastatin (−0.009 mm/y; 95% CI, −0.015 to −0.003;P =0.002). Women in the fluvastatin group had increased frequency of transiently high liver enzymes. ConclusionsThis is the first randomized trial to show that a &bgr;-blocker can reduce the rate of progression of carotid IMT in clinically healthy, symptom-free subjects with carotid plaque. This suggests that &bgr;-blockers may have a favorable effect on atherosclerosis development.

Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study

Abstract Objective To evaluate the rate of over-diagnosis of breast cancer 15 years after the end of the Malmö mammographic screening trial. Design Follow-up study. Setting Malmö, Sweden. Subjects 42 283 women aged 45-69 years at randomisation. Interventions Screening for breast cancer with mammography or not (controls). Screening was offered at the end of the randomisation design to both groups aged 45-54 at randomisation but not to groups aged 55-69 at randomisation. Main outcome measures Rate of over-diagnosis of breast cancer (in situ and invasive), calculated as incidence in the invited and control groups, during period of randomised design (period 1), during period after randomised design ended (period 2), and at end of follow-up. Results In women aged 55-69 years at randomisation the relative rates of over-diagnosis of breast cancer (95% confidence intervals) were 1.32 (1.14 to 1.53) for period 1, 0.92 (0.79 to 1.06) for period 2, and 1.10 (0.99 to 1.22) at the end of follow-up. Conclusion Conclusions on over-diagnosis of breast cancer in the Malmö mammographic screening trial can be drawn mainly for women aged 55-69 years at randomisation whose control groups were never screened. Fifteen years after the trial ended the rate of over-diagnosis of breast cancer was 10% in this age group.

Relation between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects. Results from a cross‐sectional study in Malmö, Sweden

Aims To assess whether there is an association between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects free from symptomatic cardiovascular disease.

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study

OBJECTIVE To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Prevalence of swallowing complaints and clinical findings among 50–79-year-old men and women in an urban population

To determine the prevalence of swallowing and esophageal complaints in the general population, 300 men and 300 women were asked to answer a mailed questionnaire. The participation rate was 92.5%. Complaints were reported by 35%. The most common complaints were symptoms associated with gastroesophageal reflux (GER) and globus sensation, both with a rate of occurrence of 20%. Obstruction of the bolus reported by 3% was the individual symptom that most frequently brought patients to the doctor. To validate the questionnaire and to study possible organic causes behind these symptoms, 46 persons with symptoms were invited to undergo further examination. Cineradiography of the pharynx revealed that 7 of 14 patients with symptoms of GER had abnormalities in the esophagus. Eleven of 55 patients with GER symptoms at least once a week underwent endoscopy. One case of erosive esophagitis and one case of gastric ulcer were diagnosed. Four of nine patients with obstructive symptoms had defective closure of the laryngeal vestibule shown by cineradiography. Endoscopy in four patients with obstructive symptoms revealed benign findings. Thus, an epidemiologic study of patients with swallowing symptoms documented a low incidence of serious organic disease.

Lung Function and Cardiovascular Risk Relationship With Inflammation-Sensitive Plasma Proteins

Background—The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. Methods and Results—Forced vital capacity (FVC) and plasma levels of fibrinogen, &agr; 1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to ≈25% of the excess risk. The risk factor–adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to ≈10% to 15% of the excess risk. Among men with low FVC, the risk factor–adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (≥2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (≤1 protein in top quartile; reference, top quartile of FVC and low protein levels). Conclusions—FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.

Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden.

Objective: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. Methods: Within two prospective cohorts in Umeå and Malmö we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. Results: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umeå cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; ptrend = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. Conclusions: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-1 and IGFBP-2, are associated with increased breast cancer risk.