Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In ...total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 95% CI: 1.04-1.09) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.
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.
The trace element selenium is of essential importance for the synthesis of a set of redox active proteins. We investigated three complementary serum selenium status biomarkers in relation to overall ...survival and recurrence following diagnosis of primary invasive breast cancer in a large prospective cohort study. The Sweden Cancerome Analysis Network – Breast Initiative (SCAN-B) is a prospective population-based study including multiple participating hospitals. Main analyses included 1996 patients with a new diagnosis of primary invasive breast cancer, with blood sampling at the time of diagnosis. In sera of the patients, total serum selenium, selenoprotein P (SELENOP), and glutathione peroxidase 3 (GPx3) activity was analysed. All three biomarkers showed a positive correlation (p < 0.001), supporting the high quality of samples and analytical techniques. During a total of 13,306 person years of follow-up, 310 deaths and 167 recurrent breast cancer events occurred. In fully adjusted Cox models, all three biomarkers correlated inversely with mortality (p trend <0.001) and compared with the lowest quintile, hazard ratios (95% confidence interval) for overall survival in the highest quintile of selenium, SELENOP and GPx3 were 0.42 (0.28–0.63), 0.51 (0.36–0.73) and 0.52 (0.36–0.75), respectively. Low GPx3 activity was associated with more recurrences (Q5 vs Q1: fully adjusted HR (95%CI); 0.57 (0.35–0.92), (p trend = 0.005). Patients with low selenium status according to all three biomarkers (triple deficient) had the highest mortality risk with an overall survival probability of ∼50% after 8 years, in particular as compared to those having at least one marker in the highest quintile; fully adjusted HR (95%CI); 0.30 (0.21–0.43). Prediction of mortality based on all three biomarkers outperformed established tumour characteristics like histologic grade, number of involved lymph nodes or tumour size. An assessment of Se status at breast cancer diagnosis identifies patients at exceptionally high risk for a poor prognosis.
Display omitted
•Three different serum biomarkers of selenium status are inversely associated with all-cause mortality following breast cancer diagnosis.•Lower serum glutathione peroxidase 3 activity is associated with more recurrences following breast cancer.•Patients in the lowest quintile regarding all three serum biomarkers have a particularly high all-cause mortality.
Neurotensin regulates both satiety and breast cancer growth in the experimental setting, but little is known about its role in the development of breast cancer or cardiometabolic disease in humans.
...To test if fasting plasma concentration of a stable 117-amino acid fragment from the neurotensin precursor hormone proneurotensin is associated with development of diabetes mellitus, cardiovascular disease, breast cancer, and mortality.
Proneurotensin was measured in plasma from 4632 fasting participants of the population-based Malmö Diet and Cancer Study baseline examination 1991-1994. Multivariate Cox proportional hazards models were used to relate baseline proneurotensin to first events and death during long-term follow-up until January 2009, with median follow-up ranging from 13.2 to 15.7 years depending on the disease.
Incident diabetes mellitus, cardiovascular disease, breast cancer, and mortality.
Overall, proneurotensin (hazard ratio HR per SD increment of log-transformed proneurotensin) was related to risk of incident diabetes (142 events; HR, 1.28; 95% CI, 1.09-1.50; P = .003), cardiovascular disease (519 events; HR, 1.17; 95% CI, 1.07-1.27; P < .001), and cardiovascular mortality (174 events; HR, 1.29; 95% CI, 1.12-1.49; P = .001) with a significant interaction between proneurotensin and sex (P < .001) on risk of cardiovascular disease. Exclusively in women, proneurotensin was related to incident diabetes (74 events; HR, 1.41; 95% CI, 1.12-1.77; P = .003), cardiovascular disease (224 events; HR, 1.33; 95% CI, 1.17-1.51; P < .001), breast cancer (123 events; HR, 1.44; 95% CI, 1.21-1.71; P < .001), total mortality (285 events; HR, 1.13; 95% CI, 1.01-1.27; P = .03), and cardiovascular mortality (75 events; HR, 1.50; 95% CI, 1.20-1.87; P < .001).
Fasting proneurotensin was significantly associated with the development of diabetes, cardiovascular disease, breast cancer, and with total and cardiovascular mortality.
Prospective studies have indicated that elevated blood glucose levels may be linked with increased cancer risk, but the strength of the association is unclear. We examined the association between ...blood glucose and cancer risk in a prospective study of six European cohorts.
The Metabolic syndrome and Cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden; the current study included 274,126 men and 275,818 women. Mean age at baseline was 44.8 years and mean follow-up time was 10.4 years. Excluding the first year of follow-up, 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. We used Cox regression models to calculate relative risk (RR) for glucose levels, and included adjustment for body mass index (BMI) and smoking status in the analyses. RRs were corrected for regression dilution ratio of glucose. RR (95% confidence interval) per 1 mmol/l increment of glucose for overall incident cancer was 1.05 (1.01-1.10) in men and 1.11 (1.05-1.16) in women, and corresponding RRs for fatal cancer were 1.15 (1.07-1.22) and 1.21 (1.11-1.33), respectively. Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder, and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.
Data from our study indicate that abnormal glucose metabolism, independent of BMI, is associated with an increased risk of cancer overall and at several cancer sites. Our data showed stronger associations among women than among men, and for fatal cancer compared to incident cancer. Please see later in the article for the Editors' Summary.
Selenium has been suggested to be protective regarding breast cancer risk but no overall effect has been established. Genetics may modify the effect. This study compares the effect of selenium ...exposure on breast cancer risk between women with different alleles in single-nucleotide polymorphisms (SNPs). The Malmö Cancer and Diet Study, a cohort including 17,035 women and >25 years of follow-up on breast cancer diagnosis, was used. Five promising SNPs regarding interaction with selenium exposure were selected from the literature: rs1050450, rs4880, rs3877899, rs7579, and rs71304. Selenium exposure was assessed in three ways: genetically elevated (
= 16,429), dietary intake (
= 15,891) and serum levels (
= 2037) at baseline. Cox regression and logistic regression analyses evaluated breast cancer risk from selenium exposure, stratified for the SNPs and adjusted for risk factors. A total of 1946 women were diagnosed with breast cancer. Women with T/T alleles in rs1050450 had lower breast cancer risk compared with C/C, HR 0.81 (0.68-0.96). Interaction by rs1050450 limited a protective effect of higher selenium intake to T/T carriers, HR 0.68 (0.43-1.08) for intermediate intake and HR 0.63 (0.40-1.00) for high intake. No interactions or risk differences were seen for other SNPs or for serum selenium or genetically elevated selenium. The results indicate that genetic variation in rs1050450 might affect breast cancer risk and that selenium exposure could be a possible modifiable risk factor for breast cancer among women with that variation.
To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can).
Me-Can consists of seven cohorts from Norway, Austria, ...and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation.
In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95%CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95%CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95%CI: 0.46, 0.95), and cancers of the lymph-/hematopoietic tissue (HR = 0.68, 95%CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95%CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95%CI: 0.08, 0.62), breast (HR = 0.70, 95%CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95%CI: 0.42, 0.88), and cancers of the lymph-/hematopoietic tissue (HR = 0.61, 95%CI: 0.44, 0.83).
TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.
Zinc has been suggested to play a role in breast cancer progression; however, no previous study on zinc levels and the potential effect on breast cancer survival has been conducted. This study ...investigates recurrence-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) in relation to zinc levels, in serum and diet, overall and stratified for phosphorus and selenium levels. The Malmö Diet and Cancer Study, a prospective population-based cohort in Sweden including 17,035 women, was used to identify breast cancer patients diagnosed in the period 1991–2013. Diet was assessed by a validated modified diet history method. A Cox regression analysis yielded hazard ratios (HRs) with 95% confidence intervals adjusted for potential confounders. Out of 1062 patients with invasive breast cancer, 268 recurrences, 205 breast cancer deaths and 228 deaths from other causes were recorded. No overall associations were seen between zinc and RFS, BCSS or OS. However, in women with a high phosphorus intake, a higher BCSS and OS were seen in zinc intake Q2 to Q4 versus Q1; the adjusted HR was 0.41 (0.23–0.73) and 0.64 (0.41–1.00), respectively. The results indicate that the combination of intermediate/high zinc intake and high phosphorus intake may lead to a better breast cancer survival.
Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not ...been investigated. The metabolic syndrome and cancer project (Me‐Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z‐score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z‐score. RRs were corrected for random error in measurements. During an average follow‐up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z‐score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub‐cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24–1.58), mid blood pressure 2.08 (0.95–4.73), blood glucose 2.13 (1.55–2.94) cholesterol 0.62 (0.51–0.76) and serum triglycerides 0.85 (0.65–1.10). The RR per one unit increment of the MetS z‐score was 1.35 (1.12–1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
Axillary lymph node status is one of the most important prognostic factors for breast cancer. The aim of this study was to determine predictive factors for metastasis to sentinel node (SN) in primary ...invasive breast cancer.
This is a study of 3979 patients with primary breast cancer during 2008-2013 in Malmö and Lund scheduled for surgery and included in the information retrieved from Information Network for Cancer Care (INCA). The final study population included 2552 patients with primary invasive breast cancer. The risk of metastases to SN were examined in relation to potential clinicopathological factors such as age, screening mammography, tumor size, tumor type, histological grade, estrogen status, progesterone status, Her-2 status, multifocality, and lymphovascular invasion. Binary logistic regression was used; adjusted analyses yielded odds ratio (OR) with 95% confidence interval.
Tumors detected by mammography screening were less likely to be associated with metastases to SN compared to those not found by mammography screening (0.63; 0.51-0.80). Negative hormonal status for estrogen associated with lower risk for SN metastases compared to tumor with positive estrogen status (0.64; 0.42-0.99). Tumors with a size more than 20 mm had higher risk to metastasize to SN (1.84; 1.47-2.33) compared to tumors less than 20 mm. Multifocality (1.90; 1.45-2.47) and lymphovascular invasion (3.74; 2.66-5.27) were also strong predictive factors for SN metastases.
SN metastasis is less likely to occur in women with invasive breast cancer diagnosed by screening mammogram. Tumors with negative estrogen status are associated with low risk for SN metastases. Tumors larger than 20 mm, multifocality, or lymphovascular invasion are also factors associated with high risk for SN metastases.
PDF
