Alicja Wolk

Karolinska Institutet | KI · Institute of Environmental Medicine - IMM

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addre...

Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer (CRC) screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced CRC risk model comprising 140 known CRC l...

Background: Tobacco smoking is an established risk factor for colorectal cancer (CRC). However, genetically-defined population subgroups may have increased susceptibility to smoking-related effects on CRC. Methods: A genome-wide interaction scan was performed including 33,756 CRC cases and 44,346 controls from three genetic consortia. Results:...

Background To assess the relationship between diet quality and risk of older-onset Crohn’s disease (CD) and ulcerative colitis (UC). Methods We conducted a prospective cohort study of 83,147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaire to calculate adherence scores to multiple...

Objective To estimate the proportion of cases of Crohn’s disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors. Design In a prospective cohort study of US adults from the Nurses’ Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable...

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect g...

Diabetes is an established risk factor for colorectal cancer; however, the mechanisms underlying this relationship are not fully understood and the role of genetic variation is unclear. We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction a...

Background: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ances...

Background Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. Materials and methods Data from 12 prospe...

The environmental impact of Swedish diets was assessed for six indicators (greenhouse gas [GHG] emissions, cropland use, nitrogen application, phosphorus application, consumptive water use and extinction rate), using self-reported food intake within two population-based cohorts of men and women, 56–96 years of age. The dietary environmental impact...

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructool...

Background: Dietary fibre may reduce the risk of allergy. Our aim was to investigate the association between fibre intake in childhood, asthma, allergic rhinitis and IgE sensitization up to adulthood. Methods: The individual fibre intake of 2285 participants from the Swedish population-based birth cohort BAMSE was estimated between 98- and 107-i...

Background SHapley Additive exPlanations (SHAP) based on tree-based machine learning methods have been proposed to interpret interactions between exposures in observational studies, but their performance in realistic simulations is seldom evaluated. Methods Data from population-based cohorts in Sweden of 47,770 men and women with complete baseline...

Background Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. Methods Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort...

Background: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods: We conducted a genome-wide gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen-only, and combined estrogen-progestogen therapy with CRC risk, among 28,486...

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from...

Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study's objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and...

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 obse...

Background & aims Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the anti-inflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation. Methods The study was based on two cohorts of 82,295 Swedish adults...

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype an...

Background: The etiology of Colorectal cancer(CRC) is not fully understood. Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study(n=1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2>0.01(Nmetabolite=58) were applied to predict levels of meta...

Background: Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. Methods: The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swed...

Background Cadmium (Cd) is a toxic metal, which the non-smoking population is mainly exposed to through diet. Current health-based guidance values are based on renal toxicity; however, emerging evidence suggests that bone and the cardiovascular system might be more sensitive to Cd exposure. Objective To assess the association of urinary Cd (U-Cd)...

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been associated with elevated cholesterol levels. However, data on incident cardiovascular disease (CVD) is lacking. Objectives: We investigated the association of exposure to PFAS with risk of myocardial infarction and stroke and, subsidiar...

Background: Currently known associations between common genetic variants and colorectal cancer (CRC) explain less than half of its heritability of 25%. As alcohol consumption has a Jshape association with CRC risk, non-drinking and heavy drinking are both risk factors for CRC. Methods: Individual-level data was pooled from Colon Cancer Family Regis...

Environmental exposures to a myriad of chemicals are associated with adverse health effects in humans, while good nutrition is associated with improved health. Single chemical in vivo and in vitro studies demonstrate causal links between the chemicals and outcomes, but such studies do not represent human exposure to environmental mixtures. One way...

Background Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associ...

Background Glycemic traits—such as hyperinsulinemia, hyperglycemia, and type-2 diabetes—have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glyc...

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10 –8 we...

Aims: Trials demonstrate that following the DASH diet lowers blood pressure, which may prevent development of heart failure (HF). We investigated the association between long-term adherence to the DASH diet and food substitutions within the DASH diet on the risk of HF. Methods: Men and women aged 45-83 years without previous HF, ischemic heart d...

Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin...

Background Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power...

To search for colorectal cancer (CRC) risk loci, Swedish samples were used for a genome‐wide haplotype analysis. A logistic regression model was employed in 2663 CRC cases and 1642 controls in the discovery analysis. Three analyses were done, on all, familial‐, and nonfamilial CRC samples and only results with odds ratio (OR) > 1 were analyzed. sin...

Background Salicylic acid (SA) is a metabolite that can be obtained from the diet via fruit and vegetable ingestion, of which increased consumption has observationally been shown to decrease risk of colorectal cancer (CRC). Whilst primary prevention trials of SA and CRC risk are lacking, there is strong evidence from clinical trials and prospective...

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival...

Background Dietary antioxidants may protect the lung against oxidative damage and prevent chronic respiratory disease. We aimed to investigate fruit, vegetable and antioxidant intake (measured as total antioxidant capacity, TAC) at age 8 years in relation to asthma and lung function up to 24 years. Methods In this study of 2,506 participants from...

Clinical variables—age, family history, genetics—are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age a...

Introduction: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve ass...

Background and aims Inflammation has been revealed to facilitate thrombogenesis and to increase the risk of venous thromboembolism (VTE). However, limited data are available on the association between the anti-inflammatory diet and incident VTE. We conducted a cohort analysis to examine this association and to further examine whether this associati...

Objective To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity. Methods By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged fro...

Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach...

Objective Smoking is a strong risk factor for the development of abdominal aortic aneurysm (AAA). It was hypothesised that a Mediterranean diet via its anti-oxidative properties would decrease the risk of AAA, particularly among smokers. Methods The study population included the Cohort of Swedish Men (45 072 men) and the Swedish Mammography Cohort...

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785...

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785...

Background Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER...

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31–39 years)]...

Background: Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water (<1.5mg/L, the maximum recommended by the World Health Organization) have been inconclusive. Objective: We assessed as...

Dietary climate impact in a Swedish population (56-95 years old) was estimated based on self-reported food intake from 50 000 men and women within two population-based cohorts and on climate data, covering emissions from farm to fork, for 600 foods representative for the Swedish market. Aims were to assess variation in dietary climate impact betwee...

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives: T...

PurposeRed meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes.Methods Analyses were based on Swedish case–con...

A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00786-2.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS 1 ) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS 2 (PHS 1 , adapted for OncoArray) in a multi-ethnic...

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic datas...

65 Background: Clinical variables (age, family history, and genetics) are commonly used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores, including PHS, are associated with all prostate cancer and are not specific for...

Scope A high fructose and galactose intake have shown adverse metabolic effects in animal models and in humans, but it is yet unknown if addition of fermentable dietary fiber could mitigate such effects. This study investigated the effects of high intakes of fructose and galactose, with/without added fructooligosaccharides (FOS), on metabolic facto...

Background and aims Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedi...

Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). Materials and method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European anc...

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringi...

Background/objectives: Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intake...

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospecti...

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringi...

Background We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). Methods We included 50 755 men and women from the Cohort of Swedish Men and the Swedish Mammography Cohort who answered lifestyle and medical questi...

Background Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. Methods We examined sex- and site-specific associations of adiposity with CRC risk and wh...

Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were tre...

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or famil...

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potentia...