| 1. |
- Brandt, Jasmine, et al.
(författare)
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Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:7, s. 1309-1321
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.
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| 2. |
- Clasen, Joanna L., et al.
(författare)
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Reproductive and hormonal factors and risk of renal cell carcinoma among women in the european prospective investigation into cancer and nutrition
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:14, s. 15588-15600
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
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| 3. |
- Danielsson, Frida, et al.
(författare)
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Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia
- 2018
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 9:28, s. 19730-19744
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Tidskriftsartikel (refereegranskat)abstract
- In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines of the BJ model responded strikingly different to hypoxia. Besides corroborating many of the known responses to hypoxia, we demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.
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| 4. |
- Huss, Linnea, et al.
(författare)
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Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:16
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Huss, Linnea, et al.
(författare)
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Serum levels of vitamin D, parathyroid hormone and calcium in relation to survival following breast cancer.
- 2014
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 25:9, s. 1131-1140
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D, parathyroid hormone (PTH) and calcium in blood are correlated with each other. Previous studies have suggested vitamin D to have anti-proliferative effects on tumor cells, whereas PTH may have carcinogenic effects. A cancer disease may influence calcium levels in blood, but less is known about calcium and its potential effect on cancer risk and survival. The aim of this study was to examine pre-diagnostic levels of vitamin D (25OHD), PTH and calcium in relation to survival after breast cancer.
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| 6. |
- Huss, Linnea, et al.
(författare)
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SNPs related to vitamin D and breast cancer risk : A case-control study
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. Methods: The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. Results: The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68-0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52-1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low. Conclusions: SNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.
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| 7. |
- Huss, Linnea, et al.
(författare)
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The Vitamin D Receptor as a Prognostic Marker in Breast Cancer-A Cohort Study
- 2024
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Ingår i: Nutrients. - 2072-6643. ; 16:7, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has indicated an association between the presence of the vitamin D receptor (VDR) in breast cancer tissue and a favorable prognosis. This study aimed to further evaluate the prognostic potential of VDR located in the nuclear membrane or nucleus (liganded). The VDR protein levels were analyzed using immunohistochemistry in tumor samples from 878 breast cancer patients from Lund, Sweden, included in the Breast Cancer and Blood Study (BCBlood) from October 2002 to June 2012. The follow-up for breast cancer events and overall survival was recorded until 30 June 2019. Univariable and multivariable survival analyses were conducted, both with complete case data and with missing data imputed using multiple imputation by chained equations (MICE). Tumor-specific positive nuclear membrane VDR(num) staining was associated with favorable tumor characteristics and a longer breast cancer free interval (BCFI; HR: 0.64; 95% CI: 0.44-0.95) and overall survival (OS; HR: 0.52; 95% CI: 0.34-0.78). Further analyses indicated that VDRnum status also was predictive of overall survival when investigated in relation to ER status. There were significant interactions between VDR and invasive tumor size (Pinteraction = 0.047), as well as mode of detection (Pinteraction = 0.049). VDRnum was associated with a longer BCFI in patients with larger tumors (HR: 0.36; 95% CI: 0.14-0.93) or clinically detected tumors (HR: 0.28; 95% CI: 0.09-0.83), while no association was found for smaller tumors and screening-detected tumors. Further studies are suggested to confirm our results and to evaluate whether VDR should and could be used as a prognostic and targetable marker in breast cancer diagnostics.
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| 8. |
- Huss, Linnea
(författare)
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Vitamin D and Breast Cancer. Studies on Incidence and Survival.
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Previous research has suggested beneficial effects of vitamin D on both breast cancer risk and prognosis. The overall aim of this research project was to investigate associations between vitamin D and breast cancer. The population-based prospective cohort, the Malmö Diet and Cancer Study, recruited 17,034 women in the first half of the 1990s. Studies in in the current thesis are based on blood samples collected at baseline, analyzed for levels of vitamin D, parathyroid hormone (PTH), calcium and later also used for genetic sequencing. Breast tumors that developed in women within the cohort were included in a tissue microarray and analyzed for expression of the vitamin D receptor (VDR). Specific aims were to investigate: I.Serum levels of vitamin D, PTH and calcium in relation to breast cancer survival, i.e. mortality among women diagnosed with breast cancer. II.Vitamin D-related single nucleotide polymorphisms (SNPs) and breast cancer risk.III.Expression of VDR in association with breast cancer mortality.IV.Levels of vitamin D in relation to expression of VDR in subsequent breast tumors. Results and conclusions:I.Compared to intermediate levels of vitamin D, low levels and high levels were associated with a poor survival, i.e. high risk of death related to breast cancer. No association was found between PTH and breast cancer mortality. Relatively high serum calcium levels were associated with relatively low breast cancer mortality.II.SNPs associated with levels of vitamin D did not affect breast cancer risk. One SNP, related to the vitamin D binding protein, was associated with breast cancer risk.III.VDR expression was associated with a favorable breast cancer prognosis.IV.There were indications that vitamin D levels were associated with VDR expression in a subsequent breast tumor.The association between low vitamin D levels and high breast cancer mortality may be mediated through development of a VDR-negative tumor. There was no evidence to suggest an additional beneficiary effect of vitamin D levels higher than intermediate levels.
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| 9. |
- Huss, Linnea, et al.
(författare)
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Vitamin D receptor expression in invasive breast tumors and breast cancer survival
- 2019
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis. Methods: VDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality. Results: We found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34-0.91) and 0.59 (0.30-1.16) respectively. Conclusions: This study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor.
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| 10. |
- Skarping, Ida, et al.
(författare)
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Retrospective validation study of an artificial neural network-based preoperative decision-support tool for noninvasive lymph node staging (NILS) in women with primary breast cancer (ISRCTN14341750)
- 2024
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Ingår i: BMC Cancer. - 1471-2407. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgical sentinel lymph node biopsy (SLNB) is routinely used to reliably stage axillary lymph nodes in early breast cancer (BC). However, SLNB may be associated with postoperative arm morbidities. For most patients with BC undergoing SLNB, the findings are benign, and the procedure is currently questioned. A decision-support tool for the prediction of benign sentinel lymph nodes based on preoperatively available data has been developed using artificial neural network modelling. Methods: This was a retrospective geographical and temporal validation study of the noninvasive lymph node staging (NILS) model, based on preoperatively available data from 586 women consecutively diagnosed with primary BC at two sites. Ten preoperative clinicopathological characteristics from each patient were entered into the web-based calculator, and the probability of benign lymph nodes was predicted. The performance of the NILS model was assessed in terms of discrimination with the area under the receiver operating characteristic curve (AUC) and calibration, that is, comparison of the observed and predicted event rates of benign axillary nodal status (N0) using calibration slope and intercept. The primary endpoint was axillary nodal status (discrimination, benign [N0] vs. metastatic axillary nodal status [N+]) determined by the NILS model compared to nodal status by definitive pathology. Results: The mean age of the women in the cohort was 65 years, and most of them (93%) had luminal cancers. Approximately three-fourths of the patients had no metastases in SLNB (N0 74% and 73%, respectively). The AUC for the predicted probabilities for the whole cohort was 0.6741 (95% confidence interval: 0.6255–0.7227). More than one in four patients (n = 151, 26%) were identified as candidates for SLNB omission when applying the predefined cut-off for lymph node-negative status from the development cohort. The NILS model showed the best calibration in patients with a predicted high probability of healthy axilla. Conclusion: The performance of the NILS model was satisfactory. In approximately every fourth patient, SLNB could potentially be omitted. Considering the shift from postoperatively to preoperatively available predictors in this validation study, we have demonstrated the robustness of the NILS model. The clinical usability of the web interface will be evaluated before its clinical implementation. Trial registration: Registered in the ISRCTN registry with study ID ISRCTN14341750. Date of registration 23/11/2018.
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