Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.

Background: High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

Alcohol intake and pancreatic cancer risk: An analysis from 30 prospective studies across Asia, Australia, Europe, and North America.

Background: Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.

Methods And Findings: Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America.

Mendelian randomization study of sleep traits and risk of colorectal cancer.

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits.

Association between socioeconomic position and lung cancer incidence in 16 countries: a prospective cohort consortium study.

Background: Studies have reported higher lung cancer incidence among groups with lower socioeconomic position (SEP). However, it is not known how this difference in lung cancer incidence between SEP groups varies across different geographical settings. Furthermore, most prior studies that assessed the association between SEP and lung cancer incidence were conducted without detailed adjustment for smoking.

Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: A Mendelian Randomization Study.

Background: The tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with the risk of overall and early-onset colorectal cancer.

Waist Circumference, a Body Shape Index, and Molecular Subtypes of Colorectal Cancer: A Pooled Analysis of Four Cohort Studies.

Background: Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease.

Methods: Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types).

Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses.

Background: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear.

Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons.

Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer.

It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases).

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.

Leisure time television watching, computer use and risks of breast, colorectal and prostate cancer: A Mendelian randomisation analysis.

Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal.

Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS).

Association of Metabolic Syndrome With Risk of Lung Cancer: A Population-Based Prospective Cohort Study.

Background: Both the incidence of lung cancer and the prevalence of metabolic syndrome (MetS) have been increasing worldwide. The relationship between MetS and lung cancer remains controversial.

Research Question: What is the risk of lung cancer associated with MetS and its components?

Study Design And Methods: Multivariable Cox regression models were used to estimate the hazard ratio (HR) of MetS-related variables on lung cancer risk, both overall and by histologic subtype, in the UK Biobank.

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.

Leisure time sedentary behaviour and risks of breast, colorectal, and prostate cancer: A Mendelian randomization analysis.

Unlabelled: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. We examined potential causal associations between self-reported leisure television watching and computer use and risks of breast, colorectal, and prostate cancer using a two-sample Mendelian randomization framework. Genetic variants were identified from a recent genome-wide association study (GWAS).