Showing papers by "Jonas Manjer published in 2022"

Autoimmunity to selenoprotein P predicts breast cancer recurrence

Abstract: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subjects, and in patients with thyroid disease. Given the potential transport disrupting properties, we hypothesized that breast cancer patients with SELENOP-aAb may have a poor prognosis.SELENOP-aAb along with serum Se, SELENOP and GPX3 activity were determined in serum samples of 1988 patients with a new diagnosis of breast cancer enrolled in the multicentre SCAN-B study. Patients were followed for ∼9 years and multivariate Cox regression models were applied to assess hazard ratios.Applying a cut-off based on outlier detection, we identified 7.65% of patients with SELENOP-aAb. Autoantibody titres correlated positively to total Se and SELENOP concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but independent of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI) = 1.87(1.17-2.99), particularly in patients with low Se concentrations, HR(95%CI) = 2.16(1.20-3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1.25(1.01-1.55) and 1.31(1.13-1.51), respectively.Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast cancer, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, independent of established prognostic factors, who may respond favourably to Se supplementation.

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Abstract: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

Zinc and Breast Cancer Survival: A Prospective Cohort Study of Dietary Intake and Serum Levels

Abstract: 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.

Genetic Variation Interacts with Selenium Exposure Regarding Breast Cancer Risk: Assessing Dietary Intake, Serum Levels and Genetically Elevated Selenium Levels

Abstract: 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 (n = 16,429), dietary intake (n = 15,891) and serum levels (n = 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.

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)

Abstract: Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country‐specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal‐cell carcinoma (BCC): n = 8711; squamous‐cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow‐up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1‐4.9 g/day: HR = 1.44, 95% CI = 1.17‐1.77; Ptrend = .001), BCC (HR = 1.12, 95% CI = 1.01‐1.23; Ptrend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95‐1.44; Ptrend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90‐1.30; Ptrend = .13; BCC: HR = 1.08, 95% CI = 1.00‐1.17, Ptrend = .03; melanoma: HR = 0.93, 95% CI = 0.80‐1.08, Ptrend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08‐1.99; Ptrend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04‐1.31; Ptrend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11‐1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.

Dietary intake of advanced glycation endproducts (AGEs) and cancer risk across more than 20 anatomical sites: A multinational cohort study

Abstract: Dear Editor, In the European region, which shares 22.8% of the global cancer burden for 10% of the global population, there were around 4.4million new cancer cases and 1.9million deaths from cancer in 2020 [1]. The reasons for the high cancer incidence rates are complex; however, diet and dietary components are among the main contributors to cancer risk [2]. Inmodern-day living, a growing proportion of people include in their diets ultra-processed foods. Byproducts of food processing and home-prepared foods are so-called dietary advanced glycation endproducts (AGEs), which are reactive metabolites emerging during the breakdown of reducing sugar. AGEs production is preponderant in dry high-heat processes (e.g., baking, roasting); hence foods such as cakes, crisps, crackers, cereal products, meat and meat-derived products represent a major source of dietary AGEs [3]. AGEs have been associated with chronic inflammatory diseases and may also play a role in carcinogenesis. However, the evidence from prospective human studies of the potential involvement of dietary AGEs in cancer development is limited [4–6]. This study aimed to examine the association between the intake of three well-characterized dietary AGEs, N-epsilon-carboxymethyl-lysine (CML), N-espsilon-1-carboxyethyl-lysine (CEL), and N-delta-(5hydro-5-methyl-4-imidazolon-2-yl) ornithines (MG-H1), and the risk of overall and site-specific cancers in the

Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival

Abstract: Previous research suggests associations between low systemic levels of vitamin D and poor breast cancer prognosis and between expression of the vitamin D receptor (VDR) in breast cancers and survival. This study aimed to study associations between pre-diagnostic systemic levels of vitamin D and expression of VDR in subsequent breast tumors, and interactions between vitamin D and VDR on breast cancer mortality. Systemic vitamin D levels were measured in women within the Malmö Diet and Cancer Study. The expression of VDR was evaluated immunohistochemically in a tissue microarray of subsequent breast cancers. Statistical analyses followed. Women with high levels of vitamin D had a smaller proportion of VDR negative breast tumors compared to women with low levels of vitamin D (odds ratio: 0.68; 95% confidence interval: 0.41–1.13). Vitamin D levels were not found to modify the association between low VDR expression and high breast cancer mortality. To conclude, there was no statistical evidence for an association between pre-diagnostic levels of vitamin D and the expression of VDRs in breast cancer, nor did vitamin D levels influence the association between VDR expression and breast cancer mortality. Further studies are needed in order to establish the effects of vitamin D on breast cancer.