Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk

Purpose Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer. Methods and materials This study was designed as a case–control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method. Results SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38–6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00–2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk. Conclusion Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-β.

Development and validation of dietary and lifestyle insulinemic indices among Iranian adult population

Background There is no study regarding developing a valid index to predict insulin-related disorders in the Iranian population based on their dietary habits and lifestyle. In the current study, we aimed to develop and validate insulinemic potential indices of diet and lifestyle in Iranian adults. Methods In this cross-sectional study, we analysed data of 1063 men and women aged ≥ 25 years among participants of the examination three of Tehran lipid and glucose study (TLGS) (2006–2008). Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle indices were developed using stepwise linear regression analysis based on dietary intakes, body mass index, and physical activity data. Fasting serum insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) were used as biomarkers of hyperinsulinemia (HI) and insulin resistance (IR). Validation analyses were performed in examination four of TLGS. Results We developed four indices related to insulin homeostasis, including the dietary index for HI (DIH), the dietary index for IR (DIR), the lifestyle index for HI (LIH), and the lifestyle index for IR (LIR). Based on multivariable-adjusted models, the relative values of the biomarker in subjects in the highest quartile of indices were 45% for LIH (95% CI 1.36–1.55, Ptrend < 0.001), 28% for DIR (95% CI 1.13–1.42, Ptrend = 0.019), and 51% for LIR (95% CI 1.41–1.61, Ptrend < 0.001), higher than those in the reference quartile, respectively. Conclusion We designed and validated indices to determine the insulin potential of diet and lifestyle for the Iranian population, according to Iran’s demographic and dietary intake characteristics.

Role of macronutrient intake in the epigenetics of obesity

Obesity is caused by a combination of hereditary and environmental factors. Despite extensive study, contemporary through diet, exercise, education, surgery, and pharmacological treatments, no effective long-term solution has been found to this epidemic. Over the last decade, there has been a tremendous advancement in understanding the science of epigenetics, as well as a rise in public interest in learning more about the influence of diet and lifestyle choices on the health of an individual. Without affecting the underlying DNA sequence, epigenetic alterations impact gene expression. Previous animal studies have shown a link between the type of diet and expression or suppression of obesity genes, but there are very few human studies that demonstrate the relationship between dietary intake and obesity gene expression. This review highlights the effects of carbohydrates, lipids, and protein intake from the diet on obesity-related genes.

Diet- and Lifestyle‐Based Prediction Models to Estimate Cancer Recurrence and Death in Patients With Stage III Colon Cancer (CALGB 89803/Alliance)

PURPOSE Current tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy. METHODS Using an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors. RESULTS Among 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features. CONCLUSION Diet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.

The relationship between overweight and female infertility

Excessive weight seems to negatively influence fertility, and as it is a modifiable factor, understanding this relationship can contribute to infertility treatment. Adipose tissue is responsible for releasing several hormones and cytokines related to the reproductive system, such as leptin, TNF-a, and Interleukin-6, substances that can negatively impact female fertility. Additionally, a woman's diet and lifestyle can influence body weight and fertility. Food consumption, characterized by a high intake of foods with high energy density, high levels of sugar, saturated fat, and poor nutrients, as well as physical inactivity, can favor excessive weight. Thus, losing body weight obtained through a healthy diet associated with physical activity may restore fertility in overweight women.

Indonesian Genomic Landscape of Pathogenic Mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Colorectal Cancer

Background : Knowing colorectal cancer’s heterogeneity and dynamic features, recognizing its biological behaviour requires detailed identification of mutated genes involved. Colorectal cancer (CRC) requires several mutated genes to occur and those are dissimilar in each person hence essential to be discovered in specific population. Until recently, there is no known study describing genomic landscape of CRC in Indonesian population. This study aims to describe profile of pathogenic mutation of APC, TP53, PIK3CA, KRAS, and MLH1 in CRC patients treated at 3 different hospitals in Jakarta. Methods : This is a descriptive study conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017-2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. Pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behaviour and survival were collected from medical records. Results : There were total 22 subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. Five types of mutation were identified, including nonsense, missense, frameshift, splice-site, and silent mutation. There are 4 groups of co-occurring mutations, which are APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Conclusion : Indonesia having various ethnicities with diverse diet and lifestyle has distinct profile of pathogenic mutation presenting mostly with locally-advanced stage with various outcome and survival rate.

Appraisal on Special Ayurvedic Dietary Formulas for Metabolic Syndrome

Metabolic syndrome and related complications are a major challenge for health providers of present era. Metabolic syndrome with key characters of abdominal obesity, insulin resistance, hypertension and dyslipidemia are the outcomes of faulty diet and habits. Since there are no such pharmacological agents which can reverse this condition more importance is being given to diet and lifestyle modifications. Traditional medicinal systems like Ayurveda gives equal importance for food and nutrition in both health and diseased conditions. Concept of Pathya -apathya for each and every disease is unique to Ayurveda where the macro and micronutrient principles were selected rationally for each disease conditions. These very principles can be adopted along with dietary supplements for curbing modern lifestyle disorders, more over there is mentioning of similar conditions in classics under a board term of Santharpanajanya Vikaras. Materials and methods- Thorough literary search done on various classical Ayurvedic texts for various diet and dietary preparations and online bases for their pharmacological properties from Ayurvedic and modern perspective and enlisted the dietary supplements. Results- Selected three major ingredients for the macro nutrient principles carbohydrate, protein and fat suggestive for MS from Sthoulya Prakarana and their properties are critically reviewed. Conclusion- There is enough scope of research in Ayurvedic dietary supplements for obesity and Metabolic Syndrome.

The impact of diet and lifestyle on wellbeing during COVID-19-lockdown

A healthy diet and lifestyle may protect against adverse mental health outcomes, which is especially crucial during stressful times, such as the COVID-19 pandemic. This preregistered longitudinal online study explored whether diet and lifestyle (physical activity, sleep, and social interactions) could predict wellbeing and mood during a light lockdown in Germany. Participants (N = 117, 72 males; 28 9 years old) answered mental health and lifestyle questionnaires (social connections, sleep, activity) followed by submitting one week of food and mood-lifestyle diary (food intake, positive and negative mood, mental wellbeing, sleep quality, physical activity level, quantity and quality of social interactions) via a smartphone app. We used multivariate linear and mixed-effects models to predict mood and wellbeing by using dietary components and lifestyle factors. Inter-individual analyses revealed that sleep and social interaction significantly impacted mood and wellbeing. Interestingly, fruit and vegetable intake predicted wellbeing, even when controlling for all lifestyle factors. Fruit and vegetable intake also significantly predicted daily fluctuations in wellbeing within individuals next to sleep, physical activity, and social interactions. We observed gender differences in fruit and vegetable intake and anxiety levels. Our results emphasize the importance of diet contributing to individual wellbeing, even in the challenging times of a pandemic.

Human Microbiome in Children, at the Crossroad of Social Determinants of Health and Personalized Medicine

The evolving field of microbiome research offers an excellent opportunity for biomarker identification, understanding drug metabolization disparities, and improving personalized medicine. However, the complexities of host–microbe ecological interactions hinder clinical transferability. Among other factors, the microbiome is deeply influenced by age and social determinants of health, including environmental factors such as diet and lifestyle conditions. In this article, the bidirectionality of social and host–microorganism interactions in health will be discussed. While the field of microbiome-related personalized medicine evolves, it is clear that social determinants of health should be mitigated. Furthermore, microbiome research exemplifies the need for specific pediatric investigation plans to improve children’s health.