Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK.

Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis.

Sex- and site-specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort.

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study.

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls.

Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.

Background: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.

Methods: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results.

Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations.

Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.

Impact of weight loss on cancer-related proteins in serum: results from a cluster randomised controlled trial of individuals with type 2 diabetes.

Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

Purpose: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.

Methods: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer.

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study.

Background: The association of fitness with cancer risk is not clear.

Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.

Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation.

Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer.

Identifying proteomic risk factors for overall, aggressive and early onset prostate cancer using Mendelian randomization and tumor spatial transcriptomics.

Background: Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention.

Methods: We investigated the association of 2,002 genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using -pQTL Mendelian randomization (MR) and colocalization. Findings for proteins with support from both MR, after correction for multiple-testing, and colocalization were replicated using two independent cancer GWAS, one of European and one of African ancestry.

Kidney Function and Risk of Renal Cell Carcinoma.

Background: We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors.

Methods: We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up.

Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

Background: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.

Methods: We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and SHBG (sex hormone binding globulin) in 45 431 pre-menopausal and 173 476 post-menopausal women. We performed multivariable linear regression separately for UK Biobank, EPIC (European Prospective Investigation into Cancer and Nutrition) and EHBCCG (Endogenous Hormones and Breast Cancer Collaborative Group), and meta-analysed the results.

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition.

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.