Breast cancer comprises several molecular subtypes with different prognoses and possibly different etiology. Reproductive and hormonal factors are associated with breast cancer overall, and with ...luminal subtypes, but the associations with other subtypes are unclear. We used data from a national screening program to conduct a large nested case-control study.
We conducted a nested case-control study on participants in the Norwegian Breast Cancer Screening Program in 2006 - 2014. There was information on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) for 4748 cases of breast cancer. Breast cancer subtypes were defined as luminal A-like (ER+ PR+ HER2-), luminal B-like (ER+ PR- HER2- or ER+ PR+/PR-HER2+), HER2-positive (ER- PR- HER2+) and triple-negative (ER- PR- HER2-). Conditional logistic regression was used to estimate odds ratios (ORs) of breast cancer associated with age at first birth, number of pregnancies, oral contraceptive use, intrauterine devices and menopausal hormone therapy. Analyses were adjusted for age, body mass index, education, age at menarche, number of pregnancies and menopausal status.
Number of pregnancies was inversely associated with relative risk of luminal-like breast cancers (p-trend ≤0.02), and although not statistically significant, with HER2-positive (OR = 0.60, 95% CI 0.31-1.19) and triple-negative cancer (OR = 0.70, 95% CI 0.41-1.21). Women who had ≥4 pregnancies were at >40% lower risk of luminal-like and HER2-positive cancers than women who had never been pregnant. However, there was a larger discrepancy between tumor subtypes with menopausal hormone use. Women who used estrogen and progesterone therapy (EPT) had almost threefold increased risk of luminal A-like cancer (OR = 2.92, 95% CI 2.36-3.62) compared to never-users, but were not at elevated risk of HER2-positive (OR = 0.88, 95% CI 0.33-2.30) or triple-negative (OR = 0.92, 95% CI 0.43 - 1.98) subtypes.
Reproductive factors were to some extent associated with all subtypes; the strongest trends were with luminal-like subtypes. Hormone therapy use was strongly associated with risk of luminal-like breast cancer, and less so with risk of HER2-positive or triple-negative cancer. There are clearly some, but possibly limited, etiologic differences between subtypes, with the greatest contrast between luminal A-like and triple-negative subtypes.
Not applicable.
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 increment1.07 95% CI1.04–1.09) 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% CI1.08–1.15) for men and 1.06 (95% CI1.02–1.11) 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.
To what extent alcohol, smoking, and physical activity are associated with the various subtypes of breast cancer is not clear. We took advantage of a large population-based screening cohort to ...determine whether these risk factors also increase the risk of the poor prognosis subtypes.
We conducted a matched case-control study nested within the Norwegian Breast Cancer Screening Program during 2006-2014. A total of 4,402 breast cancer cases with risk factor and receptor data were identified. Five controls were matched to each case on year of birth and year of screening. Conditional logistic regression was used to estimate ORs of breast cancer subtypes adjusted for potential confounders.
There were 2,761 luminal A-like, 709 luminal B-like HER2-negative, 367 luminal B-like HER2-positive, 204 HER2-positive, and 361 triple-negative cancers. Current alcohol consumption was associated with breast cancer risk overall OR 1.26; 95% confidence interval (CI), 1.09-1.45 comparing 6+ glasses a week to never drinkers. However, this risk increase was found only for luminal A-like breast cancer. Smoking 20+ cigarettes a day was associated with an OR of 1.41 (95% CI, 1.06-1.89) overall, with significant trends for luminal A-like and luminal B-like HER2-negative cancer. Current physical activity (4+ hours/week compared with none) was associated with 15% decreased risk of luminal A-like cancer, but not clearly with other subtypes.
In this large study, alcohol, smoking, and physical activity were predominantly associated with luminal A-like breast cancer.
Alcohol, smoking, and physical activity were associated with luminal A-like breast cancer subtype.
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Ovarian cancer is associated with high serum calcium and low serum albumin in clinical and epidemiologic studies. Whether high calcium and low albumin predispose to ovarian cancer or reflect existing ...cancer is unclear.
Test the hypothesis that serum calcium increases and serum albumin decreases in women who develop ovarian cancer.
Two hundred and four women donated sera to the Janus Serum Bank in Norway pre- and post-diagnosis of ovarian cancer, donations separated by approximately 14 years. We measured calcium and albumin in these sera and calculated the albumin-corrected calcium. Sera were adjusted for patient age and storage time.
Post-diagnosis, mean age- and storage-adjusted calcium increased, from 2.53 to 2.68 mmol/L (p < .001). Mean age- and storage-adjusted, albumin-corrected calcium increased from 2.3 to 2.7 mmol/L (p < .001). Conversely, mean age- and storage-adjusted albumin decreased, from a mean of 51.3 to 40.9 g/L (p < .001). Significant changes were observed in women with early stage and metastatic cancer.
These data support the hypothesis that calcium and albumin are serum biomarkers of extant ovarian cancer. Longitudinal changes in calcium and albumin may be useful in ovarian cancer early detection.
•We measured frozen sera from 204 women pre- and post- diagnosis of ovarian cancer, approximately 14 years apart.•Women who developed ovarian cancer showed significant increases in calcium and significant decreases in albumin.•Longitudinal changes in serum calcium and serum albumin may be useful as biomarkers of ovarian cancer.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PURPOSE: The association between vegetable and fruit consumption and risk of cancer and cardiovascular disease (CVD) has been investigated by several studies, whereas fewer studies have examined ...consumption of vegetables and fruits in relation to all-cause mortality. Studies on berries, a rich source of antioxidants, are rare. The purpose of the current study was to examine the association between intake of vegetables, fruits and berries (together and separately) and the risk of all-cause mortality and cause-specific mortality due to cancer and CVD and subtypes of these, in a cohort with very long follow-up. METHODS: We used data from a population-based prospective Norwegian cohort study of 10,000 men followed from 1968 through 2008. Information on vegetable, fruit and berry consumption was available from a food frequency questionnaire. Association between these and all-cause mortality, cause-specific mortality due to cancers and CVDs were investigated using Cox proportional hazard regression models. RESULTS: Men who in total consumed vegetables, fruit and berries more than 27 times per month had an 8–10 % reduced risk of all-cause mortality compared with men with a lower consumption. They also had a 20 % reduced risk of stroke mortality. Consumption of fruit was inversely related to overall cancer mortality, with hazard rate ratios of 0.94, 0.84 and 0.79 in the second, third and firth quartile, respectively, compared with the first quartile. CONCLUSION: Increased consumption of vegetables, fruits and berries was associated with a delayed risk of all-cause mortality and of mortality due to cancer and stroke.
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.
Purpose: To assess the association between height and risk of cancer and cancer death. Methods: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants ...from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model. Results: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06–1.09), and in men, HR 1.04 (95 % CI 1.03–1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11–1.24), and in men HR 1.12 (95 % CI 1.08–1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01–1.16), and in men, HR 1.03 (95 % CI 1.01–1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00–1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07–1.30). All these associations were independent of body mass index. Conclusion: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.
Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ...ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study.
The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS).
In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC.
In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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