| 1. |
- Borgquist, Signe, et al.
(author)
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Apo-lipoproteins, lipids and risk of cancer.
- 2016
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 138:11, s. 2648-2656
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Journal article (peer-reviewed)abstract
- The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, Jan 1(st) 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort, and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1=0.98, 95%CI: 0.95,1.01; HRadj ApoB=1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB=1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj =0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj =0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj =1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj =1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung, and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer. This article is protected by copyright. All rights reserved.
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| 2. |
- Brandt, Jasmine, et al.
(author)
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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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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:7, s. 1309-1321
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Journal article (peer-reviewed)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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| 3. |
- Helgadottir, Anna, et al.
(author)
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Genome-wide analysis yields new loci associating with aortic valve stenosis
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
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| 4. |
- Huss, Linnea, et al.
(author)
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SNPs related to vitamin D and breast cancer risk : A case-control study
- 2018
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Journal article (peer-reviewed)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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| 5. |
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| 6. |
- Melander, Olle, et al.
(author)
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Stable Peptide of the Endogenous Opioid Enkephalin Precursor and Breast Cancer Risk.
- 2015
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In: Journal of Clinical Oncology. - 1527-7755. ; 33:24, s. 81-2632
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Journal article (peer-reviewed)abstract
- In experimental studies, enkephalins (ENKs) and related opioids have been implicated as negative regulators of breast cancer development by enhancing immune-mediated tumoral defense as well as directly inhibiting cancer cells. We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk. Therefore, our objective was to measure pro-ENK A, a surrogate for mature ENK, and evaluate its predictive value for the development of breast cancer in a large population of middle-aged women and an independent study population.
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| 7. |
- Wuttke, Matthias, et al.
(author)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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