DNA methylation markers for oral pre-cancer progression: A critical review.

Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n=15), DNA-repair (n=7), cell-cycle-signalling (n=4) and apoptosis (n=3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57-63.6% versus 8-32.1%; p<0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression

Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date

SummaryBackgroundOral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk.MethodsWe identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review.ResultsThe majority of eligible studies that explored candidate gene associations for OPMD were small (N<200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n=18 studies), DNA repair (n=11 studies), cell cycle control (n=8 studies), extra-cellular matrix alteration (n=8 studies) and immune-inflammatory (n=6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNFα (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site).ConclusionCandidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer

Nutritional profile of Indian vegetarian diets--the Indian Migration Study (IMS).

BACKGROUND: The cardiovascular and other health benefits and potential harms of protein and micronutrient deficiency of vegetarian diets continue to be debated. METHODS: Study participants included urban migrants, their rural siblings and urban residents (n = 6555, mean age - 40.9 yrs) of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore. Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical activity, medical histories, as well as blood pressure, fasting blood and anthropometric measurements were collected. Nutrient databases were used to calculate nutrient content of regional recipes. Vegetarians ate no eggs, fish, poultry and meat. Using multivariate linear regression with robust standard error model, we compared the macro- and micro-nutrient profile of vegetarian and non-vegetarian diets. RESULTS: Vegetarians, (32.8% of the population), consumed greater amounts of legumes, vegetables, roots and tubers, dairy and sugar, while non-vegetarians had a greater intake of cereals, fruits, spices, salt (p < 0.01), fats and oils. Vegetarians had a higher socioeconomic status, and were less likely to smoke, drink alcohol (p < 0.0001) and engage in less physical activity (p = 0.04). On multivariate analysis, vegetarians consumed more carbohydrates (β = 7.0 g/day (95% CI: 9.9 to 4.0), p < 0.0001), vitamin C (β = 8.7 mg/day (95% CI: 4.3 to13.0), p < 0.0001) and folate (β = 8.0 mcg/day (95% CI: 3.3 to 12.7), p = 0.001) and lower levels of fat (β = -1.6 g/day (95% CI: -0.62 to -2.7), p = 0.002), protein (β = -6.4 g/day (95% CI: -5.8 to -7.0), p < 0.0001), vitamin B12 (β = -1.4 mcg/day (95% CI: -1.2 to -1.5), p < 0.0001) and zinc (β = -0.6 mg/day (95% CI: -0.4 to -0.7), p < 0.0001). CONCLUSION: Overall, Indian vegetarian diets were found to be adequate to sustain nutritional demands according to recommended dietary allowances with less fat. Lower vitamin B12 bio-availability remains a concern and requires exploration of acceptable dietary sources for vegetarians

The association between a vegetarian diet and cardiovascular disease (CVD) risk factors in India: the Indian Migration Study.

BACKGROUND: Studies in the West have shown lower cardiovascular disease (CVD) risk among people taking a vegetarian diet, but these findings may be confounded and only a minority selects these diets. We evaluated the association between vegetarian diets (chosen by 35%) and CVD risk factors across four regions of India. METHODS: Study participants included urban migrants, their rural siblings and urban residents, of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore (n = 6555, mean age-40.9 yrs). Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical history, medical history, as well as blood pressure, fasting blood and anthropometric measurements were collected. Vegetarians ate no eggs, fish, poultry or meat. Using robust standard error multivariate linear regression models, we investigated the association of vegetarian diets with blood cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, fasting blood glucose (FBG), systolic (SBP) and diastolic blood pressure (DBP). RESULTS: Vegetarians (32.8% of the study population) did not differ from non-vegetarians with respect to age, use of smokeless tobacco, body mass index, and prevalence of diabetes or hypertension. Vegetarians had a higher standard of living and were less likely to smoke, drink alcohol (p<0.0001) and were less physically active (p = 0.04). In multivariate analysis, vegetarians had lower levels of total cholesterol (β =  -0.1 mmol/L (95% CI: -0.03 to -0.2), p = 0.006), triglycerides (β =  -0.05 mmol/L (95% CI: -0.007 to -0.01), p = 0.02), LDL (β =  -0.06 mmol/L (95% CI: -0.005 to -0.1), p = 0.03) and lower DBP (β =  -0.7 mmHg (95% CI: -1.2 to -0.07), p = 0.02). Vegetarians also had decreases in SBP (β =  -0.9 mmHg (95% CI: -1.9 to 0.08), p = 0.07) and FBG level (β =  -0.07 mmol/L (95% CI: -0.2 to 0.01), p = 0.09) when compared to non-vegetarians. CONCLUSION: We found beneficial association of vegetarian diet with cardiovascular risk factors compared to non-vegetarian diet

Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date.

BACKGROUND: Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. METHODS: We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review. RESULTS: The majority of eligible studies that explored candidate gene associations for OPMD were small (N<200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n=18 studies), DNA repair (n=11 studies), cell cycle control (n=8 studies), extra-cellular matrix alteration (n=8 studies) and immune-inflammatory (n=6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNF? (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site). CONCLUSION: Candidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer

Dietary Patterns and Breast Cancer Risk: A Multi-Centre Case Control Study among North Indian Women.

Evidence from India, a country with unique and distinct food intake patterns often characterized by lifelong adherence, may offer important insight into the role of diet in breast cancer etiology. We evaluated the association between Indian dietary patterns and breast cancer risk in a multi-centre case-control study conducted in the North Indian states of Punjab and Haryana. Eligible cases were women 30⁻69 years of age, with newly diagnosed, biopsy-confirmed breast cancer recruited from hospitals or population-based cancer registries. Controls (hospital- or population-based) were frequency matched to the cases on age and region (Punjab or Haryana). Information about diet, lifestyle, reproductive and socio-demographic factors was collected using a structured interviewer-administered questionnaire. All participants were characterized as non-vegetarians, lacto-vegetarians (those who consumed no animal products except dairy) or lacto-ovo-vegetarians (persons whose diet also included eggs). The study population included 400 breast cancer cases and 354 controls. Most (62%) were lacto-ovo-vegetarians. Breast cancer risk was lower in lacto-ovo-vegetarians compared to both non-vegetarians and lacto-vegetarians with odds ratios (95% confidence intervals) of 0.6 (0.3⁻0.9) and 0.4 (0.3⁻0.7), respectively. The unexpected difference between lacto-ovo-vegetarian and lacto-vegetarian dietary patterns could be due to egg-consumption patterns which requires confirmation and further investigation

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

L’impact des subventions locales pour l’éducation des professions de la santé : l’investissement en vaut-il la peine?

Background: Local grants programs are important since funding for medical education research is limited. Understanding which factors predict successful outcomes is highly relevant to administrators. The purpose of this project was to identify factors that contribute to the publication of local medical education grants in a Canadian context. Methods: Surveys were distributed to previous Department of Innovation in Medical Education (DIME) and Department of Medicine (DOM) grant recipients (n = 115) to gather information pertaining to PI demographics and research outcomes. A backward logistic regression was used to determine the effects several variables on publication success.&nbsp; Results: The overall publication rate was 64/115 (56%). Due to missing data, 91 grants were included in the logistic regression. Variables associated with a higher rate of publication; cross departmental compared to single department OR = 2.82 (p = 0.04), being presented OR = 3.30 (p = 0.01), and multiple grant acquisition OR = 3.85 (p = 0.005)&nbsp; Conclusion: Although preliminary, our data suggest that increasing research publications from local grants may be facilitated by pooling funds across departments, making research presentations mandatory, and allowing successful researchers to re-apply.Objectif&nbsp;: Les programmes de subventions locales sont importants car le financement de la recherche en éducation médicale est limité. Il est très important pour les administrateurs de comprendre quels sont les facteurs de réussite. Le but de ce projet était d’identifier les facteurs qui, dans le contexte canadien, contribuent à la publication d’articles à l’aide de subventions locales pour l’éducation médicale. Méthodes&nbsp;: Un sondage a été réalisé auprès des anciens récipidendaires de subventions du Department of Innovation in Medical Education (DIME) et du Department of Medicine (DOM) (n=115) afin de recueillir des informations relatives à la démographie des chercheurs principaux et aux résultats de la recherche. Une régression logistique descendante a été utilisée pour déterminer les effets de plusieurs variables sur le succès des publications. Résultats&nbsp;: Le taux de publication global était de 64/115 (56&nbsp;%). En raison de données manquantes, 91&nbsp;subventions ont été incluses dans la régression logistique. Variables associées à un taux de publication plus élevé; OR inter-départements comparé à un seul département = 2,82 (p = 0,04), soumis OR = 3,30 (p = 0,01) et OR l’’obtention de plusieurs subventions = 3,85 (p = 0,005). Conclusion&nbsp;: Bien que préliminaires, nos données suggèrent que la publication de recherches à l’aide de subventions locales pourrait être facilitée en regroupant les fonds des divers départements, en rendant la présentation de recherches obligatoire et en permettant aux chercheurs dont l’article a été retenu de faire une nouvelle soumission

The impact of local health professions education grants: is it worth the investment?

Background: Local grants programs are important since funding for medical education research is limited. Understanding which factors predict successful outcomes is highly relevant to administrators. The purpose of this project was to identify factors that contribute to the publication of local medical education grants in a Canadian context.Methods: Surveys were distributed to previous Department of Innovation in Medical Education (DIME) and Department of Medicine (DOM) grant recipients (n = 115) to gather information pertaining to PI demographics and research outcomes. A backward logistic regression was used to determine the effects several variables on publication success. Results: The overall publication rate was 64/115 (56%). Due to missing data, 91 grants were included in the logistic regression. Variables associated with a higher rate of publication; cross departmental compared to single department OR = 2.82 (p = 0.04), being presented OR = 3.30 (p = 0.01), and multiple grant acquisition OR = 3.85 (p = 0.005) Conclusion: Although preliminary, our data suggest that increasing research publications from local grants may be facilitated by pooling funds across departments, making research presentations mandatory, and allowing successful researchers to re-apply.Objectif : Les programmes de subventions locales sont importants car le financement de la recherche en éducation médicale est limité. Il est très important pour les administrateurs de comprendre quels sont les facteurs de réussite. Le but de ce projet était d’identifier les facteurs qui, dans le contexte canadien, contribuent à la publication d’articles à l’aide de subventions locales pour l’éducation médicale.Méthodes : Un sondage a été réalisé auprès des anciens récipidendaires de subventions du Department of Innovation in Medical Education (DIME) et du Department of Medicine (DOM) (n=115) afin de recueillir des informations relatives à la démographie des chercheurs principaux et aux résultats de la recherche. Une régression logistique descendante a été utilisée pour déterminer les effets de plusieurs variables sur le succès des publications.Résultats : Le taux de publication global était de 64/115 (56 %). En raison de données manquantes, 91 subventions ont été incluses dans la régression logistique. Variables associées à un taux de publication plus élevé; OR inter-départements comparé à un seul département = 2,82 (p = 0,04), soumis OR = 3,30 (p = 0,01) et OR l’’obtention de plusieurs subventions = 3,85 (p = 0,005).Conclusion : Bien que préliminaires, nos données suggèrent que la publication de recherches à l’aide de subventions locales pourrait être facilitée en regroupant les fonds des divers départements, en rendant la présentation de recherches obligatoire et en permettant aux chercheurs dont l’article a été retenu de faire une nouvelle soumission