Linking population-based cohorts with cancer registries in LMIC: a case study and lessons learnt in India.

OBJECTIVES: In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry. SETTING: Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry. PARTICIPANTS: Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982-2015 (N=140 986). METHODS AND OUTCOME MEASURES: Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father's and spouse's name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source. RESULTS: There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014-2015). CONCLUSIONS: Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Time intervals and patient-level factors in oral cancer diagnostic pathways: An application of the WHO framework in India.

BACKGROUND: Oral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients. METHODOLOGY: In this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between 'prolonged (i.e., over 1 month) time intervals') and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Over a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2-4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2-6.1)) and in patients whose first doctor's opinion was 'nothing to worry' OR (=7.3 (95% CI: 2.6-20.5)). 'Correct knowledge of cancer' shortened appraisal and help-seeking intervals and 'incorrect knowledge and negative beliefs' prolonged diagnostic interval. CONCLUSION: Our findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform 'pull' strategies for cancer control in India and similar settings.

Association of Neighborhood Alcohol Environment With Alcohol Intake and Cardiovascular Risk Factors in India: Cross-Sectional Evidence From APCAPS.

There are more and more proofs about the impact of neighborhood alcohol environment on alcohol-associated events. The relationship between the neighborhood availability and accessibility of alcohol outlet with individual level of alcohol consumption along with 11 cardiovascular risk factors was explored for the first time in India using data from the 3rd follow-up of the Andhra Pradesh children and parents study (APCAPS) (n = 6156, for liquor intake and 5,641 for heart and blood vessel risk elements). In fully adjusted models, volunteers in the lowest tertile performed worse than volunteers in the highest tertile of distance to the closest alcohol outlet were more probably to exhibit less alcohol consumption (-14.40 g/day, 95% CI: -26.21, -2.59). A unit per km2 rise in alcohol outlet density in 400 m buffering area was related to a rise in waist circumference (1.45 mm, 95% CI: 0.13, 2.77), SBP (0.29 mmHg, 95% CI: 0.09, 0.49), and DBP (0.19 mmHg, 95% CI: 0.03, 0.35). A unit per 100 m rise in distance to the closest alcohol outlet was related to a rise in waist circumference (-2.39 mm, 95% CI: -4.18, -0.59), SBP (-0.41 mmHg, 95% CI: -0.68, -0.15), and DBP (-0.29 mmHg, 95% CI: -0.51, -0.07). Neighborhood availability of alcohol outlets within immediate locality of participants' households had a closer relationship with cardiovascular risk factors than that within the whole village. Public health policies designed to limit neighborhood availability and accessibility of alcohol outlets ought to be advocated in southern India.

Feasibility of investigating the association between bacterial pathogens and oral leukoplakia in low and middle income countries: A population-based pilot study in India.

BACKGROUND: Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics. METHODS: This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR). RESULTS: Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/µl vs. 0.2 ng/µl). CONCLUSIONS: This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.

Effect of supplemental nutrition in pregnancy on offspring's risk of cardiovascular disease in young adulthood: Long-term follow-up of a cluster trial from India.

BACKGROUND: Undernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world's population), where a quarter of newborns have low birth weight. We investigated whether, in an area with prevalent undernutrition, supplemental nutrition offered to pregnant women and their offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults. METHODS AND FINDINGS: The Hyderabad Nutrition Trial was a community-based nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index (BMI) of the participants was 20 kg/m2 and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-0.01 to 0.03), p = 0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p = 0.097; systolic blood pressure, 0.5 mm Hg (-0.6 to 1.6), p = 0.36; BMI, -0.13 kg/m2 (-0.75 to 0.09), p = 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2), p = 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07), p = 0.43. The limitations of this study include nonrandomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up. CONCLUSIONS: Our results showed that in an area with prevalent undernutrition, protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programmes.

A prospective study on patterns of topical steroids self-use in dermatophytoses and determinants predictive of cutaneous side effects.

Nonprescription use of topical corticosteroids (TCS) is a significant concern. This can lead to cutaneous adverse effects, altered morphology of skin disorders and chronicity of cutaneous infections. To record and analyze the patterns of TCS use in patients with tinea corporis/cruris and analyze factors determining the development of cutaneous side effects. Hundred patients with a clinical diagnosis of tinea corporis/cruris who could recall the TCS preparation/s used were included. The TCS usage patterns were recorded and analyzed. Most patients had used very potent TCS (n = 66). Most reported using TCS intermittently for duration ranging from 1 to 4 weeks (n = 78). Relapse of symptoms occurred within 1 to 2 weeks of stopping TCS, triggering reuse. Cutaneous adverse effects were present in 44 patients (striae [n = 29], hypo/depigmentation [n = 11], skin thinning [n = 8], hypertrichosis [n = 1], tinea pseudoimbricata [n = 1]). There was a significant correlation between presence of cutaneous adverse effects and the total duration of TCS use (P = .0016), duration of disease (P = .016), and total amount of TCS used (P = .012). Use for >60 days and of >32 g were associated with 89% and 96.3% (respectively) probability of developing cutaneous adverse effects. Self-use of TCS is a worrisome trend. Intermittent use is a plausible reason for development of cutaneous side effects in only 44% patients.

Laparoscopy-assisted Neocervicovaginal Reconstruction in a Rare Case of Müllerian Anomaly: Cervicovaginal Aplasia with Unicornuate Uterus.

STUDY OBJECTIVE: To demonstrate a technique of laparoscopy-assisted neocervicovaginal reconstruction in a case of cervicovaginal aplasia. DESIGN: Step-by-step demonstration of the surgery in an instructional video. SETTING: Cervicovaginal aplasia is a rare congenital anomaly that occurs in 1 in 80 000 to 100 000 live births [1]. Occasionally, there can be other associated anomalies. Epigenetic modifications of homeobox and Wnt genes (wingless-type mouse mammary tumor virus integration site family) are hypothesized to cause defects in the development of the müllerian reproductive tract by interfering with cell migration during organogenesis [2]. Our patient was a 15-year-old girl who had a unicornuate uterus along with cervicovaginal aplasia (American Society for Reproductive Medicine class Ia, Ib, and IIc and European Society of Human Reproduction and Embryology class U4a, C4, and V4). The most common approach to treat this particular anomaly is hysterectomy, but there are many reports of neocervicovaginal reconstruction with good results [3]. INTERVENTIONS: Laparoscopic assessment showed a right unicornuate uterus with hematometra, right hematosalpinx, and a left noncavitary rudimentary horn with endometriosis. A vertical incision was made over the most prominent bulging part of the uterine fundus, and the hematometra was drained. Laparoscopic inspection of the uterine cavity showed an irregular cavity with thickened endometrium. The cervical canal could not be identified. The inspection of the external genitalia revealed complete vaginal aplasia. An inverted T incision was made over the vestibule and neovagina created by blunt digital dissection. The bladder was laparoscopically mobilized down. A Maryland dissector was inserted into the uterine cavity through the incision in the fundus and directed toward the neovagina. The myometrium was then punctured while simultaneously visualizing the neovagina to create a neocervix. A 16-F Foley's catheter was then pulled into the uterine cavity with the Maryland dissector from the vaginal end. The neocervix was enlarged around the catheter and then sutured to the vestibular epithelium with 6 interrupted 1-0 polyglactin sutures. The Foley's catheter was anchored to the myometrium laparoscopically, and the uterine incision was closed with interrupted 1-0 polyglactin sutures. The right hematosalpinx was then excised. The intravaginal plastic mold was removed after 4 days. The patient was advised to use the bulb of a plastic pipette to help maintain vaginal patency. She resumed her menses 3 weeks after the surgery. Follow-up at 8 months revealed a normal-sized uterus on transabdominal ultrasound and a vaginal length of 5.5 cm on speculum examination. She currently reports regular cyclic menstruation with mild dysmenorrhea and has not yet begun sexual activity. CONCLUSION: Cervicovaginal aplasia can be successfully treated by laparoscopy-assisted neocervicovaginal reconstruction as demonstrated in the video.

Neighborhood physical food environment and cardiovascular risk factors in India: Cross-sectional evidence from APCAPS.

There has been increasing interest in associations between neighborhood food environments and cardiovascular risk factors. However, results from high-income countries remain inconsistent, and there has been limited research from low- and middle-income countries. We conducted a cross-sectional analysis of the third wave follow-up of the Andhra Pradesh children and parents study (APCAPS) (n = 5764, median age 28.8 years) in south India. We examined associations between the neighborhood availability (vendor density per km2 within 400 m and 1600 m buffers of households) and accessibility (distance from the household to the nearest vendor) of fruit/vegetable and highly processed/take-away food vendors with 11 cardiovascular risk factors, including adiposity measures, glucose-insulin, blood pressure, and lipid profile. In fully adjusted models, higher density of fruit/vegetable vendors within 400 m of participant households was associated with lower systolic blood pressure [-0.09 mmHg, 95% confidence interval (CI): -0.17, -0.02] and diastolic blood pressure (-0.10 mmHg, 95% CI: -0.17, -0.04). Higher density of highly processed/take-away food vendors within 400 m of participant households was associated with higher Body Mass Index (0.01 Kg/m2, 95% CI: 0.00, 0.01), waist circumference (0.22 mm, 95% CI: 0.05, 0.39), systolic blood pressure (0.03 mmHg, 95% CI: 0.01, 0.06), and diastolic blood pressure (0.03 mmHg, 95% CI: 0.01, 0.05). However, within 1600 m buffer, only association with blood pressure remained robust. No associations were found for between neighborhood accessibility and cardiovascular risk factors. Lower density of fruit/vegetable vendors, and higher density of highly processed/take-away food vendors were associated with adverse cardiovascular risk profiles. Public health policies regarding neighborhood food environments should be encouraged in south India and other rural communities in south Asia.

Is increasing urbanicity associated with changes in breastfeeding duration in rural India? An analysis of cross-sectional household data from the Andhra Pradesh children and parents study.

OBJECTIVE: To investigate whether village-level urbanicity and lower level socioeconomic factors are associated with breastfeeding practices in transitioning rural communities in India. SETTING: 29 villages in Ranga Reddy district, southern India between 2011 and 2014. PARTICIPANTS: 7848 children under 6 years identified via a cross-sectional household survey conducted as part of the Andhra Pradesh Children and Parents Study. OUTCOME MEASURES: Two key indicators of optimal breastfeeding: termination of exclusive breastfeeding before 6 months and discontinuation of breastfeeding by 24 months. Village urbanicity was classified as low, medium or high according to satellite assessed night-light intensity. RESULTS: Breastfeeding initiation was almost universal, and approximately two in three children were exclusively breastfed to 6 months and a similar proportion breastfed to 24 months. Using multilevel logistic regression, increasing urbanicity was associated with breastfeeding discontinuation before 24 months (medium urbanicity OR 1.45, 95% CI 0.71 to 2.96; high urbanicity OR 2.96, 95% CI 1.45 to 6.05) but not with early (<6 months) termination of exclusive breastfeeding. Increased maternal education was independently associated with both measures of suboptimal breastfeeding, and higher household socioeconomic position was associated with early termination of exclusive breastfeeding. CONCLUSION: In this transitional Indian rural community, early stage urbanicity was associated with a shorter duration of breastfeeding. Closer surveillance of changes in breastfeeding practices alongside appropriate intervention strategies are recommended for emerging economies.

Association of Hip Bone Mineral Density and Body Composition in a Rural Indian Population: The Andhra Pradesh Children and Parents Study (APCAPS).

BACKGROUND: Fat mass is variably associated with bone mass, possibly due to differential mechanical and biological effects of fat mass. We examined the association of fat mass with bone mass in a lean population. OBJECTIVE: To investigate association between hip bone mineral density and fat and lean mass in a cross-sectional study from southern India. DESIGN: The Andhra Pradesh Children and Parents Study is a prospective cohort study in Hyderabad, India. In 2009-2012, the study collected data on anthropometric measures, bone mineral density (BMD), fat mass, and lean mass measured by dual-energy x-ray absorptiometry, and socioeconomic data of the adult participants (n = 1760; mean age = 34.9 years old for women; 2130 and 32.3 for men). RESULTS: The median BMI (kg/m2) was 20.1 kg/m2. Women had relatively higher fat mass as compared to men. In models adjusted for lean mass, there was an association between hip bone mineral density and fat mass in women (ß (95% confidence interval): premenopausal 0.025 (0.006 to 0.045); postmenopausal 0.045 (0.014 to 0.076)) but not in men (0.001 (-0.012 to 0.0014)). The association between hip BMD and fat mass was stronger in postmenopausal than premenopausal women. Hip BMD was consistently associated with lean mass, in both men and women. CONCLUSIONS: In this relatively lean population, lean mass was more consistently associated with hip BMD than fat mass. Weight gain through lean mass improvement may be a more reliable public health strategy for strengthening bone health in transitional settings.

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), 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). 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.

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.

Adolescent undernutrition and early adulthood bone mass in an urbanizing rural community in India.

The long-term effects on bone health of nutritional status in adolescence are unclear. The impact of adolescent and current body mass on bone mass in young adulthood in rural India was assessed. Current lean mass was a more important determinant of bone mass than thinness during adolescence in this population. PURPOSE/INTRODUCTION: Adolescence is a crucial period for skeletal growth. However, the long-term effects on bone health of nutritional status in adolescence, particularly in the context of nutritional transition, are unclear. The current manuscript assessed the impact of adolescent and current body size on bone mass in young adulthood in an Indian rural community that is undergoing rapid socioeconomic changes. METHODS: The Andhra Pradesh Children and Parents Study is a prospective cohort study in Hyderabad, India. In 2003-2005, the study collected anthropometric and cardiovascular data on adolescents (mean age = 16 years old). The second and third waves of the study in 2009-2012 collected data on current anthropometric measures, areal bone mineral density (aBMD) in hip and lumbar spine (L1-L4) measured by dual-energy X-ray absorptiometry, and living standards of the trial participants who were now young adults (mean age = 22 years old). RESULTS: The median body mass index (BMI) of the 722 participants included in this analysis was 16.8 kg/m(2) during adolescence, while the median BMI as young adults was 19.3 kg/m(2). Lower aBMD during adulthood was associated with lower adolescent BMI (ß (95 % confidence interval) for hip aBMD 0.017 (0.013 to 0.022) and LS aBMD 0.012 (0.008 to 0.016)). This association was attenuated upon adjustment for current fat and lean mass (ß (95 % CI) for hip aBMD 0.00 (-0.005 to 0.005) and LS aBMD 0.005 (0.000 to 0.01)). There was clear evidence for positive associations between aBMDs and current lean mass. CONCLUSIONS: Current lean mass was a more important determinant of bone mass than thinness during adolescence in this population. Weight gain during late adolescence and young adulthood coupled with improvement in lean mass may help to mitigate any adverse effects that pre-adulthood undernutrition may have on bone mass accrual.

Socio-economic patterning of cardiometabolic risk factors in rural and peri-urban India: Andhra Pradesh children and parents study (APCAPS).

AIM: To assess the prevalence of cardiometabolic risk factors by socio-economic position (SEP) in rural and peri-urban Indian population. SUBJECTS AND METHODS: Cross-sectional survey of 3,948 adults (1,154 households) from Telangana (2010-2012) was conducted to collect questionnaire-based data, physical measurements and fasting blood samples. We compared the prevalence of risk factors and their clustering by SEP adjusting for age using the Mantel Hansel test. RESULTS: Men and women with no education had higher prevalence of increased waist circumference (men: 8 vs. 6.4 %, P < 0.001; women: 20.9 vs. 12.0 %, P = 0.01), waist-hip ratio (men: 46.5 vs. 25.8 %, P = 0.003; women: 58.8 vs. 29.2 %, P = 0.04) and regular alcohol intake (61.7 vs. 32.5 %, P < 0.001; women: 25.7 vs. 3.8 %, P < 0.001) than educated participants. Unskilled participants had higher prevalence of regular alcohol intake (men: 57.7 vs. 38.7 %, P = 0.001; women: 28.3 vs. 7.3 %, P < 0.001). In contrast, participants with a higher standard of living index had higher prevalence of diabetes (top third vs. bottom third: men 5.2 vs. 3.5 %, P = 0.004; women 5.5 vs. 2.4 %, P = 0.003), hyperinsulinemia (men 29.5 vs. 16.3 %, P = 0.002; women 31.1 vs. 14.3 %, P < 0.001), obesity (men 23.3 vs. 10.6 %, P < 0.001; women 25.9 vs. 12.8 %, P < 0.001), and raised LDL (men 16.8 vs. 11.4 %, P = 0.001; women 21.3 vs. 14.0 %, P < 0.001). CONCLUSIONS: Cardiometabolic risk factors are common in rural India but do not show a consistent association with SEP except for higher prevalence of smoking and regular alcohol intake in lower SEP group. Strategies to address the growing burden of cardiometabolic diseases in urbanizing rural India should be assessed for their potential impact on social inequalities in health.

Association of common genetic variants with lipid traits in the Indian population.

Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.

Y chromosome haplogroup distribution in Indo-European speaking tribes of Gujarat, western India.

The present study was carried out in the Indo-European speaking tribal population groups of Southern Gujarat, India to investigate and reconstruct their paternal population structure and population histories. The role of language, ethnicity and geography in determining the observed pattern of Y haplogroup clustering in the study populations was also examined. A set of 48 bi-allelic markers on the non-recombining region of Y chromosome (NRY) were analysed in 284 males; representing nine Indo-European speaking tribal populations. The genetic structure of the populations revealed that none of these groups was overtly admixed or completely isolated. However, elevated haplogroup diversity and FST value point towards greater diversity and differentiation which suggests the possibility of early demographic expansion of the study groups. The phylogenetic analysis revealed 13 paternal lineages, of which six haplogroups: C5, H1a*, H2, J2, R1a1* and R2 accounted for a major portion of the Y chromosome diversity. The higher frequency of the six haplogroups and the pattern of clustering in the populations indicated overlapping of haplogroups with West and Central Asian populations. Other analyses undertaken on the population affiliations revealed that the Indo-European speaking populations along with the Dravidian speaking groups of southern India have an influence on the tribal groups of Gujarat. The vital role of geography in determining the distribution of Y lineages was also noticed. This implies that although language plays a vital role in determining the distribution of Y lineages, the present day linguistic affiliation of any population in India for reconstructing the demographic history of the country should be considered with caution.

Cohort profile: Andhra Pradesh Children and Parents Study (APCAPS).

The Andhra Pradesh Children and Parents Study (APCAPS) was originally established to study the long-term effects of early-life undernutrition on risk of cardiovascular disease. Its aims were subsequently expanded to include trans-generational influences of other environmental and genetic factors on chronic diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT) conducted in 1987-90 to compare the effects on birthweight of a protein-calorie supplement for pregnant women and children. The index children of HNT and their mothers were retraced and examined in 2003-05, and the children re-examined as young adults aged 18-21 years in 2009-10. The cohort was expanded to include both parents and siblings of the index children in a recently completed follow-up conducted in 2010-12 (N=∼6225 out of 10,213 participants). Recruitment of the remaining residents of these 29 villages (N=∼55,000) in Ranga Reddy district of Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle, medical, anthropometric, physiological, vascular and body composition measures, DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS participants are available. Details of how to access these data are available from the corresponding author.