A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Filaggrin Mutation Status and Prevention of Atopic Dermatitis with Maternal Probiotic Supplementation.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive  effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Upper Gastrointestinal Cancers and the Role of Genetic Testing.

Beyond the few established hereditary cancer syndromes with an upper gastrointestinal cancer component, there is increasing recognition of the contribution of novel pathogenic germline variants (gPVs) to upper gastrointestinal carcinogenesis. The detection of gPVs has potential implications for novel treatment approaches of the index cancer patient as well as long-term implications for surveillance and risk-reducing measures for cancer survivors and far-reaching implications for the patients' family. With widespread availability of multigene panel testing, new associations may be identified with germline-somatic integration being critical to determining true causality of novel gPVs. Comprehensive cancer care should incorporate both somatic and germline testing.

Integration and usability of a digital cancer risk stratification tool to optimize identification of patients at risk for hereditary cancers: A pilot study.

BACKGROUND: Patients with a personal or family history of cancer may have elevated risk of developing future cancers, which often remains unrecognized due to lapses in screening. This pilot study assessed the usability and clinical outcomes of a cancer risk stratification tool in a gynecologic oncology clinic. METHODS: New gynecologic oncology patients were prompted to complete a commercially developed personal and family history-based risk stratification tool to assess eligibility for genetic testing using National Comprehensive Cancer Network criteria and estimated lifetime breast cancer risk using the Tyrer-Cuzick model. After use of the risk stratification tool, usability was assessed via completion rate and the System Usability Scale, and health literacy was assessed using the BRIEF Health Literacy Screening Tool. RESULTS: 130 patients were prompted to complete the risk stratification tool; 93 (72%) completed the tool. Race and ethnicity and insurance type were not associated with tool completion. The median System Usability Scale score was 83 out of 100 (interquartile range, 60-95). Health literacy positively correlated with perceived usability. Public insurance and race or ethnicity other than non-Hispanic White was associated with lower perceived usability. Sixty (65%) patients met eligibility criteria for genetic testing, and 21 (38% of 56 eligible patients) were candidates for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of ≥20%. CONCLUSIONS: A majority of patients completed the digital cancer risk stratification tool. Older age, lower health literacy, public insurance, and race or ethnicity other than non-Hispanic White were associated with lower perceived tool usability.

Young Women's Perspectives on Being Screened for Hereditary Breast and Ovarian Cancer Risk During Routine Primary Care.

PURPOSE: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. METHODS: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FINDINGS: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. CONCLUSION: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation.

Association analysis of the IKZF4 gene with Alopecia Areata in the Chinese Han population.

Objective: The IKZF4(Ikaros family zinc finger 4) gene encodes Eos, a zinc finger transcription factor that belongs to the Ikaros family. High expression of Eos on Treg cells is important for the suppression of autoimmune responses and immune homeostasis. It has been suggested that the SNP in IKZF4 may influence the pathogenesis of AA(alopecia areata). The purpose of this study was to explore the relationship between IKZF4 polymorphism and AA in the Chinese Han population. Methods: We examined 459 patients and 434 controls in this study. The rs1701704 polymorphism was evaluated using HRM analysis and direct sequencing. Results: The prevalence of the C/C, A/C, and A/A genotypes in AA patients was 7.4%, 37.5% and 55.1%, respectively. There were significant differences in genotype distribution and allele frequencies between AA and the control group (P < .0001). The frequency of the C allele in the AA group was significantly higher (P < .0001), and the frequencies of the C allele and C/C genotype in patients with family history were higher (P < .0001; P = .001). Conclusions: The rs1701704 SNP of IKZF4 may be a genetic marker for assessing the risk of AA in the Chinese Han population.

Genetic Determinants of Selenium Availability, Selenium-Response, and Risk of Polycystic Ovary Syndrome.

Selenium is a trace element and its deficiency has been associated with the risk of PCOS, a multifactorial syndrome that affects a large number of women worldwide. Several databases and literature were searched to find out genetic variants of the genes involved in selenium uptake, metabolism, and regulation which may be significantly associated with the risk of PCOS through Se-related pathways. Genes that require selenium for their biological actions to perform were also shortlisted. A total of eighteen significantly associated genes with forty-four variants were identified as candidate variants that could play a potential role in the modulation of PCOS risk among the study population. The genetic variant distribution data was available in-house and was obtained through a GWAS study of the North India population. In silico tools were applied to understand the functional impact of these variants. Three variants namely LDLR (rs2228671), TNF (rs1041981), and SAA2 (rs2468844) are strongly associated with PCOS risk and have a functional impact on encoded protein. Certain variants of Se uptake genes such as DIO1, GPX2, TXNRD1, DIO2 and GPX3 are also significantly associated with the risk of PCOS development. "C" allele of the Se transporter gene SELENOP (rs9686343) significantly increases PCOS risk. Other potential genes require selenium for their biological actions and are involved in the inflammatory, antioxidant response, and energy homeostasis signaling pathways. Thus, genetic variants of the population may affect the Se availability in the body. Also, deficiency of Se effects may get modulated due to underlying genetic polymorphism of Se-associated genes. This information may be helpful in dosage adjustment of Se supplementation for a population in order to get maximum benefits.

Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.

The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Germline mutational variants of Turkish ovarian cancer patients suspected of Hereditary Breast and Ovarian Cancer (HBOC) by next-generation sequencing.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135-2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC.

Germline Mutations and Ancestry in Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results. RECENT FINDINGS: Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.

Association of Glycated Hemoglobin With a Risk of Pancreatic Cancer in High-Risk Individuals Based on Genetic and Family History.

INTRODUCTION: Screening for pancreatic cancer (PC) is suggested for high-risk individuals. Additional risk factors may enhance early detection in this population. METHODS: Retrospective cohort study among patients with germline variants and/or familial pancreatic cancer in an integrated healthcare system between 2003 and 2019. We calculated the incidence rate (IR) by risk category and performed a nested case-control study to evaluate the relationship between HbA1C and PC within 3 years before diagnosis (cases) or match date (controls). Cases were matched 1:4 by age, sex, and timing of HbA1c. Logistic regression was performed to assess an independent association with PC. RESULTS: We identified 5,931 high-risk individuals: 1,175(19.8%) familial PC, 45(0.8%) high-risk germline variants ( STK11, CDKN2A ), 4,097(69.1%) had other germline variants ( ATM, BRCA 1, BRCA 2, CASR, CDKN2A, CFTR, EPCAM, MLH1, MSH2, MSH6, PALB2, PRSS1, STK11, and TP53 ), and 614(10.4%) had both germline variants and family history. Sixty-eight patients (1.1%) developed PC; 50% were metastatic at diagnosis. High-risk variant was associated with greatest risk of PC, IR = 85.1(95% confidence interval: 36.7-197.6)/10,000 person-years; other germline variants and first-degree relative had IR = 33 (18.4, 59.3), whereas IR among ≥2 first-degree relative alone was 10.7 (6.1, 18.8). HbA1c was significantly higher among cases vs controls (median = 7.0% vs 6.4%, P = 0.02). In multivariable analysis, every 1% increase in HbA1c was associated with 36% increase in odds of PC (odds ratio 1.36, 95% confidence interval: 1.08-1.72). Pancreatitis was independently associated with a risk of PC (odds ratio 3.93, 95% confidence limit 1.19, 12.91). DISCUSSION: Risk of PC varies among high-risk individuals. HbA1c and history of pancreatitis may be useful additional markers for early detection in this patient population.

Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations-A Qualitative Study.

We sought to explore the intrafamilial communication and cascade genetic testing (CGT) experiences of patients with hereditary cancer from diverse, medically underserved populations and their relatives. Participants included patients receiving oncology care at an urban, safety net hospital in Texas or comprehensive cancer center in Alabama and their first-degree relatives. In-depth semi-structured qualitative interviews were completed wherein patients shared their experiences with genetic counseling (GC), genetic testing (GT), and communicating their results to relatives. Relatives shared their experiences receiving information from the patient and considering CGT. Interviews were transcribed, coded, and themes were identified. Of 25 participating patients, most recalled key aspects of GC and their GT results. Most (80%) patients shared their results with relatives, but only some relatives underwent CGT; patients reported low perceived susceptibility to hereditary cancer as a common barrier to CGT for their relatives. Of 16 participating relatives, most reported feeling distress upon learning the patient's GT results. Relatives were fearful of learning their own CGT results but identified prevention and early detection as CGT benefits. Interviews identified opportunities during family communication to improve relatives' perceived susceptibility to hereditary cancer. Tailored resources may support patients and relatives experiencing distress and fear during GT. PREVENTION RELEVANCE: This study of intrafamilial communication and cascade genetic testing experiences of patients with hereditary cancer and their relatives from diverse, medically underserved populations identified relatives' perceived susceptibility to hereditary cancer risks, distress, and fear as frequent reactions and barriers to testing. These results may inform future hereditary cancer prevention efforts.

Perioperative genetic testing and time to surgery in patients with breast cancer.

BACKGROUND: Time to treatment has been identified as a quality metric, with longer time to treatment associated with poorer outcomes. Genetic evaluation is an integral part of treatment counseling for patients with breast cancer. With expanding indications for genetic testing and consideration of expansion of genetic testing to all patients with a personal history of breast cancer, this study aims to evaluate the effect of genetic evaluation on the time interval from initial surgical visit to surgery. METHODS: A retrospective review of patients undergoing upfront surgery for stage 0-3 breast cancer from June 2022 to December 2022. Patient demographics, treatment characteristics, National Comprehensive Cancer Network criteria for genetic testing, and results were obtained. RESULTS: The study included 492 patients (489 females). Eighty-one (16.2%) were ≤50 years of age at diagnosis. In total, 281 patients (57.1%) met National Comprehensive Cancer Network criteria for genetic testing and 199 consulted with a genetic counselor (72.4%). Seventy-six patients (27.6%) not meeting National Comprehensive Cancer Network criteria pursued genetic counseling. In total, 218 patients (79.3%) referred for genetic counseling completed testing. Mean turnaround time to genetic testing result was 11 days (range, 6-66 days). Twenty-six patients (11.9%) had a pathogenic or likely pathogenic variant. Twenty-four of these patients met National Comprehensive Cancer Network testing criteria (92.3%) and 2 did not (7.7%). The time to treatment for patients undergoing genetic testing was 33 vs 34 days in those without testing (P = .45). Three patients (11.5%) with pathogenic or likely pathogenic variants altered their initial surgical plan due to their genetic testing results. Seven patients with pathogenic or likely pathogenic variant results returning postoperatively did not undergo additional surgery. CONCLUSION: Hereditary breast cancer evaluation and genetic testing did not appear to delay time to treatment for patients with breast cancer in our study cohort.

Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

Universal Germline-Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision-Making.

BACKGROUND: Whereas the National Comprehensive Cancer Network (NCCN) criteria restrict germline-genetic testing (GGT) to a subset of breast cancer (BC) patients, the American Society of Breast Surgeons recommends universal GGT. Although the yield of pathogenic germline variants (PGV) in unselected BC patients has been studied, the practicality and utility of incorporating universal GGT into routine cancer care in community and rural settings is understudied. This study reports real-world implementation of universal GGT for patients with breast cancer and genetics-informed, treatment decision-making in a rural, community practice with limited resources. METHODS: From 2019 to 2022, all patients with breast cancer at a small, rural hospital were offered GGT, using a genetics-extender model. Statistical analyses included Fisher's exact test, t-tests, and calculation of odds ratios. Significance was set at p < 0.05. RESULTS: Of 210 patients with breast cancer who were offered GGT, 192 (91.4%) underwent testing with 104 (54.2%) in-criteria (IC) and 88 (45.8%) out-of-criteria (OOC) with NCCN guidelines. Pathogenic germline variants were identified in 25 patients (13.0%), with PGV frequencies of 15 of 104 (14.4%) in IC and ten of 88 (11.4%) in OOC patients (p = 0.495). GGT informed treatment for 129 of 185 (69.7%) patients. CONCLUSIONS: Universal GGT was successfully implemented in a rural, community practice with > 90% uptake. Treatment was enhanced or de-escalated in those with and without clinically actionable PGVs, respectively. Universal GGT for patients with breast cancer is feasible within rural populations, enabling optimization of clinical care to patients' genetic profile, and may reduce unnecessary healthcare, resource utilization.

[The lipidosis in the liver of the dairy cow: Part 2 Genetic predisposition and prophylaxis]. / Die Leberverfettung der Milchkuh: Teil 2.

Hepatic lipidosis in dairy cows is the result of a disturbed balance between the uptake of non-esterified fatty acids (NEFA), their metabolism in the hepatocytes, and the limited efflux of TG as very-low-density lipoprotein (VLDL). Lipidosis and the associated risk for ketosis represents a consequence of selecting dairy cows primarily for milk production without considering the basic physiological mechanisms of this trait. The overall risk for lipidosis and ketosis possesses a genetic background and the recently released new breeding value of the German Holstein Friesian cows now sets the path for correction of this risk and in that confirms the assumed genetic threat. Ectopic fat deposition in the liver is the result of various steps including lipolysis, uptake of fat by the liver cell, its metabolism, and finally release as very-low-density lipoprotein (VLDL). These reactions may be modulated directly or indirectly and hence, serve as basis for prophylactic measures. The pertaining methods are described in order to support an improved understanding of the pathogenesis of lipidosis and ketosis. They consist of feeding a glucogenic diet, restricted feeding during the close-up time as well as supplementation with choline, niacin, carnitine, or the reduction of milking frequency. Prophylactic measures for the prevention of ketosis are also included in this discussion.

Diet-Wide Association, Genetic Susceptibility and Colorectal Cancer Risk: A Prospective Cohort Study.

BACKGROUND: Both genetic and dietary factors play significant roles in the etiology of colorectal cancer (CRC). To evaluate the relationship between certain food exposures and the risk of CRC, we carried out a large-scale association analysis in the UK Biobank. METHODS: The associations of 139 foods and nutrients' intake with CRC risk were assessed among 118,210 participants. A polygenic risk score (PRS) of CRC was created to explore any interaction between dietary factors and genetic susceptibility in CRC risk. The hazard ratio (HR) and 95% confidence interval (CI) of CRC risk linked to dietary variables and PRS were estimated using Cox regression models. Multiple comparisons were corrected using the error discovery rate (FDR). RESULTS: During a mean follow-up of 12.8 years, 1466 incidents of CRC were identified. In the UK Biobank, alcohol and white bread were associated with increased CRC risk, and their HRs were 1.08 (95% CI: 1.03-1.14; FDRP = 0.028) and 1.10 (95% CI: 1.05-1.16; FDRP = 0.003), whereas dietary fiber, calcium, magnesium, phosphorus, and manganese intakes were inversely associated. We found no evidence of any PRS-nutrient interaction relationship in relation to CRC risk. CONCLUSIONS: Our results show that higher intakes of alcohol and white bread are associated with increased CRC risk, whilst dietary fiber, calcium, magnesium, phosphorus, and manganese are inversely associated.

Disentangling the complexity of psoriasis in the post-genome-wide association era.

In recent years, genome-wide association studies (GWAS) have been instrumental in unraveling the genetic architecture of complex diseases, including psoriasis. The application of large-scale GWA studies in psoriasis has illustrated several associated loci that participate in the cutaneous inflammation, however explaining a fraction of the disease heritability. With the advent of high-throughput sequencing technologies and functional genomics approaches, the post-GWAS era aims to unravel the functional mechanisms underlying the inter-individual variability in psoriasis patients. In this review, we present the key advances of psoriasis GWAS in under-represented populations, rare, non-coding and structural variants and epistatic phenomena that orchestrate the interplay between different cell types. We further review the gene-gene and gene-environment interactions contributing to the disease predisposition and development of comorbidities through Mendelian randomization studies and pleiotropic effects of psoriasis-associated loci. We finally examine the holistic approaches conducted in psoriasis through system genetics and state-of-the-art transcriptomic analyses, discussing their potential implication in the expanding field of precision medicine and characterization of comorbidities.

Breast/ovarian cancer genetic counseling: Do anxiety, depression, and health care-related fears influence cancer worry and risk perception?

BACKGROUND: The impact of family and personal cancer history and emotional factors, such as depression and anxiety, on disease representation has received limited attention in studies investigating the development of cancer-related worry and risk perception within the context of genetic counseling. The current study endeavors to fill this gap by exploring the extent to which depression and anxiety influence cancer worry and risk perception, and the role of health care-related fear as potential mediator in this relationship. METHODS: A sample of 178 women who underwent their first genetic counseling for breast/ovarian cancer, 52% of whom had previous cancer diagnoses, completed questionnaires assessing sociodemographic and clinical information, emotional distress in terms of anxiety and depression, cancer-related worry, risk perception, and health care-related fears. RESULTS: Results of mediation analyses showed that cancer-related worry and risk perception increased with rising levels of depression and anxiety, with health care-related fears acting as a mediator in the relationship of depression and anxiety with cancer worry and risk perception. Covariate analysis revealed that previous cancer diagnosis increases cancer-related worry but not risk perception, while the number of family members affected by cancer increases both outcomes. CONCLUSION: These findings emphasize the need for a holistic approach in genetic counseling and have implications for the clinical practice.