Publications by authors named "Harvey Risch"
Article Synopsis
- The American Cancer Society suggests that doctors should talk to women about endometrial cancer risks when they reach menopause, but more younger women under 50 are being diagnosed.
- A study looked at nearly 14,000 women with endometrial cancer and found that factors like body weight and diabetes increase the risk for both younger and older women.
- Educating women about these risk factors could help reduce the number of cases, as many endometrial cancer cases in both age groups are linked to these factors.
Article Synopsis
- The Article-in-Press has been withdrawn due to serious concerns raised by the scientific community regarding its citations, methodology, and conclusions.
- Despite the authors' submission of a revised manuscript, independent peer-reviewers found it did not adequately address the issues that led to the initial concerns.
- The authors dispute the withdrawal decision and the reasons behind it, indicating a disagreement with the journal’s actions.
Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic Cancer Risk.
Cancer Epidemiol Biomarkers Prev
September 2024
Article Synopsis
- - The study investigates how genetic variants affect the relationship between heavy alcohol consumption and the risk of pancreatic cancer, utilizing data from a sizable European ancestry population.
- - Researchers identified a new relevant genomic region (10p11.22) linked to pancreatic cancer risk and a specific SNP (rs7898449) that suggests this association is influenced by heavy alcohol consumption.
- - The findings highlight the potential role of the neuropilin 1 gene in pancreatic cancer development, offering new insights into cancer risk factors, especially among heavy drinkers.
Article Synopsis
- The study examined risk factors for epithelial ovarian cancer (EOC) among women of different racial and ethnic backgrounds, including Asian, Hispanic, Native Hawaiian/Pacific Islander, and White participants.
- Findings indicated that oral contraceptive (OC) use and childbirth (parity) were generally associated with lower EOC risk across all groups, especially in Native Hawaiian/Pacific Islander and Asian women.
- Significant differences in EOC risk factors were detected among the ethnic groups, suggesting that including more diverse populations in research could improve prevention strategies for ovarian cancer.
To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).
View Article and Find Full Text PDFBackground: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear.
View Article and Find Full Text PDFBackground: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).
Methods: We analyzed >22 million variants for 398,238 women.
Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e.
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- The study investigates DNA methylation changes in individuals with hepatocellular carcinoma (HCC), looking at saliva samples from patients and matched controls to explore their potential for HCC screening.* -
- Out of 25 candidate genes linked to HCC, 16 showed detectable differences in DNA methylation between HCC cases and controls, indicating possible biomarkers for the disease.* -
- The findings suggest that using saliva for DNA testing could be a convenient and effective alternative to blood tests for HCC screening, warranting further research in this area.*
Host immunity involves various immune cells working in concert to achieve balanced immune response. Host immunity interacts with tumorigenic process impacting disease outcome. Clusters of different immune cells may reveal unique host immunity in relation to breast cancer progression.
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- A study analyzed data from 7,207 endometrial cancer cases and 22,027 controls to investigate the impact of night shift work and sleep duration on endometrial cancer risk among postmenopausal women.
- The findings indicated a non-significant inverse relationship between night shift work and endometrial cancer, meaning it did not appear to increase risk significantly.
- Additionally, the duration of sleep (short or long) did not correlate with an increased risk of endometrial cancer, although an inverse association was noted specifically for obese women.
Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.
Cancer Epidemiol Biomarkers Prev
September 2023
Article Synopsis
- The study investigated whether genetic predisposition to nonalcoholic fatty liver disease (NAFLD) increases the risk of pancreatic cancer using Mendelian randomization methods.
- Data from multiple genome-wide association studies involving thousands of individuals were analyzed, using various statistical methods to predict the genetic heritability of NAFLD.
- Results showed no association between genetically predicted NAFLD and pancreatic cancer risk, suggesting that any observed links might instead stem from related metabolic issues like obesity or diabetes.
Background: In Western populations, pancreatic ductal adenocarcinoma (PDAC) risk has been found to be greater among individuals with non-O blood types than those with O blood type. However, the association has not been fully evaluated with respect to FUT2 (determining secretor status) and FUT3 (determining Lewis antigens) status, two biologically important genes in the expression of ABO blood groups with PDAC.
Methods: We examined interactions in data from 8,027 cases and 11,362 controls in large pancreatic cancer consortia (PanScan I-III and PanC4) by using genetic variants to predict ABO blood groups (rs505922 and rs8176746), secretor status (rs601338), and Lewis antigens (rs812936, rs28362459, and rs3894326).
Background: In randomized trials in women with breast cancer, exercise has been shown to have beneficial effects on cancer-related circulating biomarkers that may impact survival. Such studies are lacking for ovarian cancer.
Methods: This secondary analysis of a published randomized controlled trial examined the impact of a 6-month exercise intervention versus attention-control on change in prespecified circulating biomarkers (cancer antigen 125 (CA-125), C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), insulin and leptin) in a subset of participants who provided a fasting blood draw (N = 104/144) at enrollment and at 6 months.
Background: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown.
Methods: We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis.
Immune checkpoint PD-1 and its ligand PD-L1 lead to T cell exhaustion, and a high level of circulating soluble PD-L1 at baseline indicates a poor prognosis in melanoma and other solid tumor types. Here we show that the dynamic changes of circulating soluble PD-1 and PD-L1 across the course of immune checkpoint blockades (ICBs) and their changes associate with patient survival in melanoma in a retrospective study. A high change of soluble PD-L1 level at a time-point but not PD-1 significantly increased the mortality, whereas a high change of soluble PD-1/PD-L1 ratio significantly reduced the mortality.
View Article and Find Full Text PDFBackground: 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 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated.
Article Synopsis
- This study examines the genetic factors contributing to the risk of different cancers by analyzing data from 12 genome-wide association studies, involving nearly 910,000 participants.
- Researchers discovered 15 new cancer susceptibility loci and found that some genetic variants are shared between multiple cancer types, despite much of the heritability being specific to individual cancers.
- The findings indicate the importance of using larger sample sizes for more effective cross-cancer analyses, which could unveil additional genetic regions linked to increased cancer risk.
Article Synopsis
- Researchers created endometrial cancer risk prediction models using data from postmenopausal White women in 19 studies to improve interventions and screenings for this rising cancer risk.
- The models demonstrated modest predictive ability, with area under the curve values (ranging from 0.64 to 0.69), and the addition of genetic factors slightly improved predictions in some cohorts.
- The epidemiologic-based model effectively identified high-risk women but showed variations in performance across different cohorts, indicating a need for refinement and adaptation for diverse populations.
Background: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.
View Article and Find Full Text PDFObjective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.
Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.
Background: Several clinical and tumour factors impact on ovarian cancer survival. It is important to evaluate if germline mutations impact long-term outcomes among patients with epithelial ovarian cancer.
Methods: We followed 1422 Ontario women with ovarian cancer.
eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.
Cancer Epidemiol Biomarkers Prev
September 2022
Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability.
Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression.
Reproductive Factors Do Not Influence Survival with Ovarian Cancer.
Cancer Epidemiol Biomarkers Prev
April 2022
Background: Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes.
Methods: Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype.