Body-mass index, blood pressure, and cause-specific mortality in India: a prospective cohort study of 500 810 adults.

BACKGROUND: The association between cause-specific mortality and body-mass index (BMI) has been studied mainly in high-income countries. We investigated the relations between BMI, systolic blood pressure, and mortality in India. METHODS: Men and women aged 35 years or older were recruited into a prospective study from the general population in Chennai, India between Jan 1, 1998, and Dec 31, 2001. Participants were interviewed (data collected included age, sex, education, socioeconomic status, medical history, tobacco smoking, and alcohol intake) and measured (height, weight, and blood pressure). Deaths were identified by linkage to Chennai city mortality records and through active surveillance by household visits from trained graduate non-medical fieldworkers. After the baseline survey, households were visited once in 2002-05, then biennially until 2015. During these repeat visits, structured narratives of any deaths that took place before March 31, 2015, were recorded for physician coding. During 2013-14, a random sample of participants was also resurveyed as per baseline to assess long-term variability in systolic blood pressure and BMI. Cox regression (standardised for tobacco, alcohol, and social factors) was used to relate mortality rate ratios (RRs) at ages 35-69 years to systolic blood pressure, BMI, or BMI adjusted for usual systolic blood pressure. FINDINGS: 500 810 participants were recruited. After exclusion of those with chronic disease or incomplete data, 414 746 participants aged 35-69 years (mean 46 [SD 9]; 45% women) remained. At recruitment, mean systolic blood pressure was 127 mm Hg (SD 15), and mean BMI was 23·2 kg/m2 (SD 3·8). Correlations of resurvey and baseline measurements were 0·50 for systolic blood pressure and 0·88 for BMI. Low BMI was strongly associated with poverty, tobacco, and alcohol. Of the 29 519 deaths at ages 35-69 years, the cause was vascular for 14 935 deaths (12 504 cardiac, 1881 stroke, and 550 other). Vascular mortality was strongly associated with systolic blood pressure: RRs per 20 mm Hg increase in usual systolic blood pressure were 2·45 (95% CI 2·16-2·78) for stroke mortality, 1·74 (1·64-1·84) for cardiac mortality, and 1·84 (1·75-1·94) for all vascular mortality. Although BMI strongly affected systolic blood pressure (an increase of about 1 mm Hg per kg/m2) and diabetes prevalence, BMI was little related to cardiac or stroke mortality, with only small excesses even for grade 1 obesity (ie, BMIs of 30·0-35·0 kg/m2). After additional adjustment for usual systolic blood pressure, BMI was inversely related to cardiac and stroke mortality throughout the range 15·0-30·0 kg/m2: when underweight participants (ie, BMI 15·0-18·5 kg/m2) were compared with overweight participants (ie, BMI 25·0-30·0 kg/m2), the blood-pressure-adjusted RR was 1·28 (95% CI 1·20-1·38) for cardiac mortality and 1·46 (1·22-1·73) for stroke mortality. INTERPRETATION: In this South Asian population, BMI was little associated with vascular mortality, even though increased BMI is associated with increased systolic blood pressure, which in turn is associated with increased vascular mortality. Hence, some close correlates of below-average BMI must have important adverse effects, which could be of relevance in all populations. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK.

Tobacco chewing and adult mortality: a case-control analysis of 22,000 cases and 429,000 controls, never smoking tobacco and never drinking alcohol, in South India.

BACKGROUND: Tobacco is consumed in both smoking and smokeless forms in India. About 35-40% of tobacco consumption in India is in the latter. The study objective was to describe the association between chewing tobacco and adult mortality. MATERIALS AND METHODS: A case-control study was conducted in urban (Chennai city) and rural (Villupuram district) areas in Tamil Nadu state in South India. Interviewed in 1998-2000 about 80,000 families (48,000 urban and 32,000 rural) with members who had died during 1995-1998. These were the cases and their probable underlying cause of death was arrived at by verbal autopsy. Controls were 600,000 (500,000 urban, 100,000 rural) individuals from a survey conducted during 1998-2001 in the same two study areas from where cases were included. RESULTS: Mortality analyses were restricted to non-smoking non-drinkers aged 35-69. The age, sex, education and study area adjusted mortality odds ratio was 30% higher (RR:1.3, 95%CI:1.2-1.4) in ever tobacco chewers compared to never chewers and was significant for deaths from respiratory diseases combined (RR:1.5, 95%CI:1.4-1.7), respiratory tuberculosis (RR:1.7, 95%CI:1.5-1.9), cancers all sites combined (RR:1.5, 95%CI:1.4-1.7) and stroke (RR:1.4, 95%CI:1.2-1.6). Of the cancers, the adjusted mortality odds ratio was significant for upper aero-digestive, stomach and cervical cancers. Chewing tobacco caused 7.1% of deaths from all medical causes. CONCLUSIONS: The present study is the first large study in India analysing non-smoking non-drinkers. Statistically significant excess risks were found among ever tobacco chewers for respiratory diseases combined, respiratory tuberculosis, stroke and cancer (all sites combined) compared to never tobacco chewers.

Cancer mortality in India: a nationally representative survey.

BACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health.

Social inequalities, tobacco chewing, and cancer mortality in south India: a case-control analysis of 2,580 cancer deaths among non-smoking non-drinkers.

OBJECTIVE: The objective of this work was to describe the relationships between educational level, tobacco chewing, and cancer mortality in south India, among middle-aged adults who never smoked tobacco or drank alcohol, to eliminate confounding by those habits. METHODS: This case-control study was conducted in two areas of Tamil Nadu state. The cases studied were 2,580 lifelong non-smoking non-drinkers who died at age 35-69 years during 1995-1998, with interviews in 1998-2000 of a spouse, neighbour, or close associate, who retrospectively provided information on the education and chewing/other habits of the deceased. Underlying neoplastic cause of death was determined by verbal autopsy. The controls were 429,306 lifelong non-smoking non-drinkers aged 35-69 from these two study areas, interviewed during 1998-2001. RESULTS: Among the controls, prevalence of current tobacco chewing was much higher in those with less education, irrespective of sex, urban/rural residence, or birth year. Compared with never chewers, ever chewers had fivefold higher mortality from mouth cancer (odds ratio 4.9, 95% confidence interval 3.5-6.8), and 1.5 to twofold higher mortality from cancers of the pharynx/larynx/oesophagus combined, stomach, and cervix. Each of these cancers had a strong, independent, inverse association with educational level. CONCLUSION: This study supports a substantial body of evidence that tobacco chewing can cause mouth cancer, and adds to evidence that chewing may increase the risk of cancer at other sites. The analysis suggests a possible link with cervical cancer, but this could have been because of residual confounding by social factors. Avoidance of tobacco chewing would avert many cancer deaths in south India, especially for people who have received relatively little formal education.

Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: a case-control study in an Indian population.

BACKGROUND: Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case-control study in an Indian population. METHODS: The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression. RESULTS: The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR=1.55; 95% CI, 1.05-2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR=2.15; 95% CI, 1.04-4.32). A substantial increase of both colon (OR=10.81; 95% CI, 1.11-107.22) and rectal (OR=4.80; 95% CI, 0.94-35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR=4.69; 95% CI, 0.84-23.87) or rectal cancer (OR=5.68; 95% CI, 1.79-22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases. CONCLUSION: Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.

Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case-control study in an Indian population.

PURPOSE: Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene-gene and gene-environment in a case-control study of an Indian population. METHODS: This case-control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR-RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression. RESULTS: The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04-2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46-1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43-9.44). CONCLUSIONS: The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.

Physical activity levels among urban and rural women in south India and the risk of breast cancer: a case-control study.

Breast cancer (BC) incidence in India is approximately 100% higher among urban women than rural women. The role of household activities (HA) among urban and rural women in the development of BC was investigated. The study was conducted between 2002 and 2005, at the Regional Cancer Center, Trivandrum and three cancer hospitals in Chennai. Cases (735 urban and 1131 rural) were women with histologically confirmed incident BC. Controls (631 urban and 1242 rural) were age-matched women, who accompanied cancer patients to the hospital. Using in-person interview, information on time spent on HA and potential confounding variables was collected. Odds ratio (OR) and 95% confidence intervals (CI) of BC were estimated according to the time spent on HA through logistic regression models. Time spent on HA was longer among rural women (urban vs. rural: 48 vs. 59% in Trivandrum and 31 vs. 41% in Chennai for 5 or more hours/day on HA). The risk of BC declined with increasing time spent on HA. Compared with less than 3 h/day, the ORs for 5-6 h/day were 0.48 (95% CI: 0.32-0.72) in premenopausal and 0.49 (95% CI: 0.34-0.72) in postmenopausal women. Corresponding ORs for 6 or more hours/day were 0.70 (95% CI: 0.48-1.02) and 0.51 (95% CI: 0.35-0.73). The study supports the hypothesis that a high level of physical activity (PA) contributes to the difference in BC risk between urban and rural women in India. The proportion of BC avoided because of moderate or high PA was estimated to be 19% in urban women and 38% in rural women.

Smoking, drinking and incident tuberculosis in rural India: population-based case-control study.

BACKGROUND: To investigate the extent to which smoking and/or drinking can increase the incidence of pulmonary tuberculosis (TB), a population-based case-control study was conducted in rural south India. METHODS: A total of 1839 males and 870 females treated in 2000-03 by state TB clinics were interviewed at home in 2004-05 about their education, smoking and drinking habits before disease onset. As controls, 2134 men and 2119 women without TB were randomly chosen from case villages and interviewed. Incidence rate ratios (RRs) are from logistic regression, adjusted for age and education. RESULTS: No women smoked or drank. The main analyses are of men aged 35-64 years, 949 cases treated for new pulmonary TB and 1963 controls. In the study, 81.5% of the cases and 55.2% of the controls had ever smoked, yielding a standardized ever- vs never-smoker TB incidence RR of 2.7 [95% confidence interval (CI) 2.2-3.3, P < 0.00001). Among control ever-smokers 96% still smoked, 71% used only bidis (mean 17 per day) and 28% used only cigarettes (mean 7 per day). After additional adjustment for alcohol, this RR was 2.2 (95% CI 1.7-2.7, P < 0.00001), but even among those who had never drunk alcohol the standardized ever- vs never-smoker RR was 2.6 (95% CI 2.0-3.6, P < 0.00001). The corresponding RRs for ever- vs never-drinking were somewhat less extreme: 2.2 (95% CI 1.8-2.6, P < 0.00001) without adjustment for smoking, 1.5 (95% CI 1.2-1.9, P = 0.00004) with adjustment for smoking and 2.1 (95% CI 1.4-3.0, 2P = 0.0001) among those who had never smoked. Among control ever-drinkers, 96% still drank and 99% used only spirits (mean 0.3 l/week). CONCLUSIONS: This study of reliably confirmed disease (by the criteria of state TB clinics) demonstrates an increased incidence of pulmonary TB among those who smoke and among those who drink. The effects of smoking after adjustment for drinking were more definite than those of drinking after adjustment for smoking.

Breastfeeding and breast cancer risk in India: a multicenter case-control study.

Breast cancer incidence is low in India compared with high-income countries, but it has increased in recent decades, particularly among urban women. The reasons for this pattern are not known although they are likely related to reproductive and lifestyle factors. Here, we report the results of a large case-control study on the association between breastfeeding and breast cancer risk. The study was conducted in 2 areas in South India during 2002-2005 and included 1,866 cases and 1,873 controls. Detailed information regarding menstruation, reproduction, breastfeeding and physical activity was collected through in-person interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression models. Breastfeeding for long duration was common in the study population. Lifetime duration of breastfeeding was inversely associated with breast cancer risk among premenopausal women (p-value of linear trend, 0.02). No such protective effect was observed in postmenopausal women, among whom a protective effect of parity was suggested. A reduction of breast cancer risk with prolonged breastfeeding was shown among premenopausal women. Health campaign focusing on breastfeeding behavior by appropriately educating women would contribute to reduce breast cancer burden.

Indoor air pollution from solid fuels and risk of hypopharyngeal/laryngeal and lung cancers: a multicentric case-control study from India.

BACKGROUND: A recent monograph by the International Agency for Research on Cancer (IARC) has identified indoor air pollution from coal usage as a known human carcinogen, while that from biomass as a probable human carcinogen. Although as much as 74% of the Indian population relies on solid fuels for cooking, very little information is available on cancer risk associated with these fuels in India. METHODS: Using data from a multicentric case-control study of 799 lung and 1062 hypopharyngeal/laryngeal cancer cases, and 718 controls, we investigated indoor air pollution from various solid fuels as risk factors for these cancers in India. RESULTS: Compared with never users, individuals who always used coal had an increased risk of lung cancer [odds ratio (OR) 3.76, 95% confidence interval (CI) 1.64-8.63]. Long duration of coal usage (>50 years) was a risk factor for hypopharyngeal (OR 3.47, CI 0.95-12.69) and laryngeal (OR 3.65, CI 1.11-11.93) cancers. An increased risk of hypopharyngeal cancer was observed among lifelong users of wood (OR 1.62, CI 1.14-2.32), however this was less apparent among never-smokers. Increasing level of smokiness inside the home was associated with an increasing risk of hypopharyngeal and lung cancer (P(trend) < 0.05). CONCLUSION: This study showed differential risks associated with indoor air pollution from wood and coal burning, and provides novel evidence on cancer risks associated with solid fuel usage in India. Our findings suggest that reducing indoor air pollution from solid fuels may contribute to prevention of these cancers in India, in addition to tobacco and alcohol control programs.

A nationally representative case-control study of smoking and death in India.

BACKGROUND: The nationwide effects of smoking on mortality in India have not been assessed reliably. METHODS: In a nationally representative sample of 1.1 million homes, we compared the prevalence of smoking among 33,000 deceased women and 41,000 deceased men (case subjects) with the prevalence of smoking among 35,000 living women and 43,000 living men (unmatched control subjects). Mortality risk ratios comparing smokers with nonsmokers were adjusted for age, educational level, and use of alcohol. RESULTS: About 5% of female control subjects and 37% of male control subjects between the ages of 30 and 69 years were smokers. In this age group, smoking was associated with an increased risk of death from any medical cause among both women (risk ratio, 2.0; 99% confidence interval [CI], 1.8 to 2.3) and men (risk ratio, 1.7; 99% CI, 1.6 to 1.8). Daily smoking of even a small amount of tobacco was associated with increased mortality. Excess deaths among smokers, as compared with nonsmokers, were chiefly from tuberculosis among both women (risk ratio, 3.0; 99% CI, 2.4 to 3.9) and men (risk ratio, 2.3; 99% CI, 2.1 to 2.6) and from respiratory, vascular, or neoplastic disease. Smoking was associated with a reduction in median survival of 8 years for women (99% CI, 5 to 11) and 6 years for men (99% CI, 5 to 7). If these associations are mainly causal, smoking in persons between the ages of 30 and 69 years is responsible for about 1 in 20 deaths of women and 1 in 5 deaths of men. In 2010, smoking will cause about 930,000 adult deaths in India; of the dead, about 70% (90,000 women and 580,000 men) will be between the ages of 30 and 69 years. Because of population growth, the absolute number of deaths in this age group is rising by about 3% per year. CONCLUSIONS: Smoking causes a large and growing number of premature deaths in India.

Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India.

Hypopharyngeal and laryngeal cancers are among the most common cancers in India. In addition to smoking, tobacco chewing may be a major risk factor for some of these cancers in India. Using data from a multicentric case-control study conducted in India that included 513 hypopharyngeal cancer cases, 511 laryngeal cancer cases and 718 controls, we investigated smoking and chewing tobacco products as risk factors for these cancers. Bidi smoking was a stronger risk factor compared to cigarette smoking for cancer of the hypopharynx (OR(bidi) 6.80 vs. OR(cig) 3.82) and supraglottis (OR(bidi) 7.53 vs. OR(cig) 2.14), while the effect of the 2 products was similar for cancer of the glottis (OR(bidi) 5.32 vs. OR(cig) 5.74). Among never-smokers, tobacco chewing was a risk factor for hypopharyngeal cancer, but not for laryngeal cancer. In particular, the risk of hypopharyngeal cancer increased with the use of Khaini (OR 2.02, CI 0.81-5.05), Mawa (OR 3.17, CI 1.06-9.53), Pan (OR 3.34, CI 1.68-6.61), Zarda (OR 3.58, CI 1.20-10.68) and Gutkha (OR 4.59, CI 1.21-17.49). A strong dose-response relationship was observed between chewing frequency and the risk of hypopharyngeal cancer (p(trend) < 0.001). An effect of alcohol on cancer of the hypopharynx and supraglottis was observed only among daily drinkers (OR 2.22, CI 1.11-4.45 and OR 3.76, CI 1.25-11.30, respectively). In summary, this study shows that chewing tobacco products commercially available in India are risk factors for hypopharyngeal cancer, and that the potency of Bidi smoking may be higher than that of cigarette smoking for hypopharyngeal and laryngeal cancers.

Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population.

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.

Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population.

PURPOSE: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population. METHODS: In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied. RESULTS: The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10-2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08-3.57) and rectal cancer (OR=1.51; 95% CI: 1.04-2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29-5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27-0.79 of 2-3 servings/day, and OR=0.31; 95% CI: 0.18-0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28-0.82). CONCLUSION: These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.

Prospective study of one million deaths in India: rationale, design, and validation results.

BACKGROUND: Over 75% of the annual estimated 9.5 million deaths in India occur in the home, and the large majority of these do not have a certified cause. India and other developing countries urgently need reliable quantification of the causes of death. They also need better epidemiological evidence about the relevance of physical (such as blood pressure and obesity), behavioral (such as smoking, alcohol, HIV-1 risk taking, and immunization history), and biological (such as blood lipids and gene polymorphisms) measurements to the development of disease in individuals or disease rates in populations. We report here on the rationale, design, and implementation of the world's largest prospective study of the causes and correlates of mortality. METHODS AND FINDINGS: We will monitor nearly 14 million people in 2.4 million nationally representative Indian households (6.3 million people in 1.1 million households in the 1998-2003 sample frame and 7.6 million people in 1.3 million households in the 2004-2014 sample frame) for vital status and, if dead, the causes of death through a well-validated verbal autopsy (VA) instrument. About 300,000 deaths from 1998-2003 and some 700,000 deaths from 2004-2014 are expected; of these about 850,000 will be coded by two physicians to provide causes of death by gender, age, socioeconomic status, and geographical region. Pilot studies will evaluate the addition of physical and biological measurements, specifically dried blood spots. Preliminary results from over 35,000 deaths suggest that VA can ascertain the leading causes of death, reduce the misclassification of causes, and derive the probable underlying cause of death when it has not been reported. VA yields broad classification of the underlying causes in about 90% of deaths before age 70. In old age, however, the proportion of classifiable deaths is lower. By tracking underlying demographic denominators, the study permits quantification of absolute mortality rates. Household case-control, proportional mortality, and nested case-control methods permit quantification of risk factors. CONCLUSIONS: This study will reliably document not only the underlying cause of child and adult deaths but also key risk factors (behavioral, physical, environmental, and eventually, genetic). It offers a globally replicable model for reliably estimating cause-specific mortality using VA and strengthens India's flagship mortality monitoring system. Despite the misclassification that is still expected, the new cause-of-death data will be substantially better than that available previously.

Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma on colorectal cancer in an Indian population.

The aim of the present study was to investigate associations between Pro12Ala and C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and colorectal cancer (CRC) risk. We recruited 301 newly diagnosed CRC patients and 291 healthy control subjects at the Madras Cancer Institute in Chennai, India, from 1999 to 2001. Genotypes of the Pro12Ala and C161T polymorphisms were determined using the PCR-RFLP method. After adjustment for age, sex, smoking habit, family history and family income, an increased risk of CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36), whereas no significant association was found for Pro12Ala (odds ratio = 1.06, 95% confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a significant difference in haplotype frequencies between cases and controls (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two polymorphisms and CRC risk was not significantly modified by dietary intake of fish. Although the biological mechanisms of the observed association remain to be elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma gene is related to risk of CRC. Further research is needed to investigate functional implications of polymorphisms of the PPAR-gamma gene in CRC development.

Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India.

BACKGROUND: Registration of the fact of death is almost complete in the city of Chennai and not so in the rural Villupuram district in Tamilnadu, India. The cause of death is often inadequately recorded on the death certificate in developing countries like India. A special verbal autopsy (VA) study of 48,000 adult (aged >or= 25 yrs) deaths in the city of Chennai (urban) during 1995-97 and 32,000 in rural Villupuram during 1997-98 was conducted to arrive at the probable underlying cause of death to estimate cause specific mortality. METHODS: A ten day training on writing verbal autopsy (VA) report for adult deaths was given to non-medical graduates with at least 15 years of formal education. They interviewed surviving spouse/close associates of the deceased to write a verbal autopsy report in local language (Tamil) on the complaints, symptoms, signs, duration and treatment details of illness prior to death. Each report was reviewed centrally by two physicians independently. Random re-interviewing of 5% of the VA reports was done to check the reliability and reproducibility of the VA report. The validity of VA diagnosis was assessed only for cancer deaths. RESULTS: Verbal autopsy reduced the proportion of deaths attributed to unspecified and unknown causes from 54% to 23% (p < 0.0001) in urban and from 41% to 26% (p < 0.0001) in rural areas in Tamilnadu for adult deaths (>or= 25). The sensitivity of VA to identify cancer was 95% in the age group 25-69. CONCLUSION: A ten day training programme to write verbal autopsy report with adequate feed back sessions and random sampling of 5% of the verbal autopsy reports for re-interview worked very well in Tamilnadu, to arrive at the probable underlying cause of death reliably for deaths in early adult life or middle age (25-69 years) and less reliably for older ages (70+). Thus VA is practicable for deaths in early adult life or middle age and is of more limited value in old age.

Tobacco survey among youth in South India.

BACKGROUND: Smoking of cigarettes and, particularly, of "bidis" (which consist of about 0.2-0.3 gm of tobacco rolled up in the leaf of another plant (temburni) has been widespread for many decades among men in India. There have, however, been no substantial studies on the prevalence of tobacco use among youth in India. Hence a Global Youth Tobacco Survey was conducted in schools in Tamil Nadu as part of on-going Global Youth Tobacco survey in over 150 countries in the world. METHODS: The two-stage cluster sample method was used to select 100 schools with standards 8, 9 and 10 in Tamil Nadu. The survey used self administered questionnaires, which consisted of 88 multiple choice questions. RESULTS: A total of 4820 students participated (a response rate of 90.1%) in the 99 of 100 schools selected for the survey. About 10% of students aged 13-15 in Tamil Nadu had ever used tobacco. Significantly higher percentages of current tobacco users (one in three students) compared to never tobacco users thought smoking or chewing tobacco makes a boy or girl more attractive. About 3 in 4 current smokers expressed a wish to stop smoking and a similar proportion have already tried to quit the habit. About 80% of students considered using tobacco (smoking or chewing tobacco) to be harmful to their health. Only about half of the students reported that they have been taught in school the health effects of tobacco use during the year preceding the survey. Exposure to environmental tobacco smoke and pro-tobacco advertisements is high. CONCLUSIONS: The tobacco prevalence among girls is alarming. The results of the survey show the need to increase awareness about health hazards of tobacco use among students. Tobacco control programs focusing on youth are essential in order to reduce the burden of tobacco related diseases in India. Repeat surveys would help in monitoring the tobacco epidemic in the school and to evaluate the efficacy of state level tobacco control programs.

Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India.

In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered.