Showing papers by "Jonas Manjer published in 2021"

Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following breast cancer diagnosis: A multicentre cohort study.

Abstract: 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. (Less)

Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults.

Abstract: Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.

Is cadmium a risk factor for breast cancer - results from a nested case-control study using data from the Malmö Diet and Cancer Study

Abstract: Background: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. Methods: All breast cancers in the Malmo Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991–1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. Results: Mean BCd was 0.51 μg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05–1.36] per μg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05–1.73)] for BCd more than 1.20 μg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 μg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. Conclusions: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. Impact: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Abstract: Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Ne-carboxy-methyllysine (CML), Ne-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Serum zinc and dietary intake of zinc in relation to risk of different breast cancer subgroups and serum levels as a marker of intake: a prospective nested case-control study.

Abstract: Zinc has been suggested to be protective against breast cancer, but the evidence remains inconclusive. One reason for inconsistent findings in previous studies may be that zinc only influences the risk of developing certain subtypes of breast cancer. Our study is the first study assessing zinc levels in relation to the risk of different breast cancer subgroups, defined by their tumor characteristics. In addition, we analyze serum zinc as a marker of dietary intake. The Malmo Diet and Cancer Study is a population-based cohort study that took place 1991–1996 in Malmo, Sweden. Until end of follow-up, 31 December 2013, 1186 incident cases were identified and matched to an equal number of controls. Odds ratios (ORs) for breast cancer, and having a certain tumor characteristic, were estimated in quartiles of baseline serum zinc and zinc intake and adjusted for potential confounders. No associations were found between zinc, measured in serum or diet pre-diagnostically, and breast cancer risk. The adjusted OR for breast cancer in serum zinc Q4 compared to Q1 was 1.09 (0.85–1.41) and in zinc intake Q4 versus Q1 was 0.97 (0.77–1.23). Moreover, there were no clear associations between zinc and any breast cancer characteristics. The kappa value, 0.025 (P = 0.022), showed poor agreement between serum zinc and zinc intake. Our findings indicate that there is no clear association between zinc and overall breast cancer risk or risk of different breast cancer subgroups. Finally, our results suggest that serum zinc is a poor marker of zinc intake.

Risk of breast cancer in relation to dietary intake of selenium and serum selenium as a marker of dietary intake: a prospective cohort study within The Malmö Diet and Cancer Study

Abstract: Selenium has been suggested to be protective against breast cancer, but the evidence remains inconclusive. Hence, it is important to further examine the potential protective effect. This prospective cohort study investigates pre-diagnostic selenium intake in relation to breast cancer risk. In addition, we analyze serum selenium as a marker of dietary intake. This study includes 17,035 women in the Malmo Diet and Cancer cohort. Dietary assessment and serum samples were collected at baseline (1991–1996). During 344,584 person-years of follow-up, 1,427 incident cases were retrieved. Cox regression analysis examined breast cancer risks adjusted for potential confounding factors. In addition, odds ratios (ORs) were estimated for 1186 cases and an equal number of controls in relation to quartiles (Q) of selenium intake and groups consisting of a combination of intake and serum selenium levels. No overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk was found. The adjusted relative risk for breast cancer in selenium intake Q4 versus Q1 was 0.96 (0.83–1.12) (Ptrend = 0.65). Similarly, adjusted the OR for breast cancer in selenium intake for Q4 versus Q1 was 0.97 (0.76–1.23). The kappa value, 0.096 (p = 0.001), showed poor agreement between serum selenium and selenium intake. Our findings suggest that there is no overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk. Finally, our results showed a poor correlation between estimated selenium intake and serum selenium.

The inverse association of body mass index with lung cancer: Exploring residual confounding, metabolic aberrations and within-person variability in smoking

Abstract: Background: The inverse observational association between body mass index (BMI) and lung cancer risk remains unclear. We assessed whether the association is explained by metabolic aberrations, residual confounding, and within-person variability in smoking, and compared against other smoking-related cancers. Methods: We investigated the association between BMI, and its combination with a metabolic score (MS) of mid-blood pressure, glucose, and triglycerides, with lung cancer and other smoking-related cancers in 778,828 individuals. We used Cox regression, adjusted and corrected for within-person variability in smoking (status/pack-years), calculated from 600,201 measurements in 221,958 participants. Results: Over a median follow-up of 20 years, 20,242 smoking-related cancers (6,735 lung cancers) were recorded. Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer [HR per standard deviation increase, 0.87 (95% confidence interval 0.85–0.89)]. Individuals with BMI less than 25 kg/m2 and high MS had the highest risk [HR 1.52 (1.44–1.60) vs. BMI ≥25 with low MS]. These associations were weaker and nonsignificant among nonsmokers. Similar associations were observed for head and neck cancers and esophageal squamous cell carcinoma, whereas for other smoking-related cancers, we generally observed positive associations with BMI. Conclusions: The increased lung cancer risk with low BMI and high MS is unlikely due to residual confounding and within-person variability in smoking. However, similar results for other cancers strongly related to smoking suggest a remaining, unknown, effect of smoking. Impact: Extensive smoking-adjustments may not capture all the effects of smoking on the relationship between obesity-related factors and risk of smoking-related cancers.

Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Abstract: (1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992–2000 and December 2013–December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.