Biomedical subjects
Vendhan Gajalakshmi
Publications and source records attributed to Vendhan Gajalakshmi.
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.
Commentary: verbal autopsy procedure for adult deaths.
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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.
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.
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 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.
Human papillomavirus and risk factors for cervical cancer in Chennai, India: a case-control study.
To evaluate the role of human papillomavirus (HPV) and other risk factors in the aetiology of invasive cervical carcinoma (ICC), we conducted a hospital-based case-control study in Chennai, Southern India. A total of 205 ICC cases (including 12 adenocarcinomas) and 213 frequency age-matched control women were included. HPV DNA in cervical cells was evaluated by means of a polymerase chain-reaction assay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed by means of unconditional multiple logistic regression models. HPV infection was detected in all but one ICC cases and in 27.7% of control women (OR = 498). Twenty-three different HPV types were found. HPV 16 was the most common type in either cases or controls, followed by HPV 18 and 33. The association of ICC with HPV 18 and HPV 16-associated types was somewhat stronger than the one with HPV 16. Multiple HPV infections did not show a higher OR for ICC than single infections. Other than HPV infection, high parity (OR for >4 vs. </=2 births = 7.3), a woman's report of her husband's extramarital sexual relationships (OR = 10.0) and early menopause (OR for <45 vs. >/=45 years = 4.2) were significantly associated with ICC, also after restricting the analysis to HPV-positive cases and controls. Poor hygienic conditions were associated with an increased risk of HPV infection among control women but not with ICC risk among HPV-positive women. A vaccine against HPV 16 and 18 may be effective in more than three-quarters of ICC in the study area.
Smoking and mortality from tuberculosis and other diseases in India: retrospective study of 43000 adult male deaths and 35000 controls.
BACKGROUND: In India most adult deaths involve vascular disease, pulmonary tuberculosis, or other respiratory disease, and men have smoked cigarettes or bidis (which resemble small cigarettes) for several decades. The study objective was to assess age-specific mortality from smoking among men (since few women smoke) in urban and in rural India. METHODS: We did a case-control study of the smoking habits of 27000 urban and 16000 rural men who had died in the state of Tamil Nadu, southern India, from medical causes (ie, any cause other than accident, homicide, or suicide), and of 20000 urban and 15000 rural male controls. The main analyses are of mortality at ages 25-69 years. FINDINGS: In the urban study area, the death rates from medical causes of ever smokers were double those of never smokers (standardised risk ratio at ages 25-69 years 2.1 [95% CI 2.0-2.2]). The risks were substantial both for cigarette smoking (the main urban habit) and for bidi smoking. Of this excess mortality among smokers, a third involved respiratory disease, chiefly tuberculosis (4.5 [4.0-5.0], smoking-attributed fraction 61%), a third involved vascular disease (1.8 [1.7-1.9], smoking-attributed fraction 24%), 11% involved cancer (2.1 [1.9-2.4], smoking-attributed fraction 32%), chiefly of the respiratory or upper digestive tracts, and 14% involved alcoholism or cirrhosis (3.3 [2.9-3.8], not attributed to smoking). Among ever smokers, the absolute excess mortality from tuberculosis was substantial throughout the age range 25-69 years. (A separate survey of 250000 men living in the urban study area found that ever smokers are three times as likely as never smokers to report a history of tuberculosis, corresponding to a higher rate of progression of chronic subclinical infection to clinical disease.) The proportional excesses of respiratory, vascular, and neoplastic mortality at ages 25-69 years among ever smokers in the urban study area were replicated, each with similarly narrow CI for the risk ratio, in the rural study area (where bidi smoking predominated), and are taken to be largely or wholly causal. For urban and for rural death from medical causes at older ages (> or =70 years), the standardised risk ratio was 1.3. INTERPRETATION: Smoking, which increases the incidence of clinical tuberculosis, is a cause of half the male tuberculosis deaths in India, and of a quarter of all male deaths in middle age (plus smaller fractions of the deaths at other ages). At current death rates, about a quarter of cigarette or bidi smokers would be killed by tobacco at ages 25-69 years, those killed at these ages losing about 20 years of life expectancy. Overall, smoking currently causes about 700000 deaths per year in India, chiefly from respiratory or vascular disease: about 550000 men aged 25-69 years, about 110000 older men, and much smaller numbers of women (since few women smoke).
Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men.
Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case-control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose-response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26-5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07-5.22) and 2.83 (95% CI 2.18-3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42-4.64) and that of esophageal cancers was 3.41 (95% CI 1.46-7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2-4 years before the interview.
Verbal autopsy of 48 000 adult deaths attributable to medical causes in Chennai (formerly Madras), India.
BACKGROUND: In the city of Chennai, India, registration of the fact of death is almost complete but the cause of death is often inadequately recorded on the death certificate. A special verbal autopsy (VA) study of 48 000 adult deaths in Chennai during 1995-97 was conducted to arrive at the probable underlying cause of death and to measure cause specific mortality rates for Chennai. METHODS: Trained non-medical graduates with at least 15 years of formal education interviewed the surviving family members or an associate of the deceased to write a report on the complaints, symptoms, signs, duration and treatment details of illness prior to death. Each report was reviewed centrally by two physicians independently. The reliability was assessed by comparing deaths attributed to cancer by VA with records in Vital Statistics Department and Chennai Cancer Registry. RESULTS: The VA reduced the proportion of deaths attributed to unspecified medical causes and unknown causes from 37% to 7% in early adult life and middle age (25-69 yrs) and has yielded fewer unspecified causes (only 10%) than the death certificate. The sensitivity of VA to identify cancer was 94% in the age group 25-69. CONCLUSION: VA is practicable for deaths in early adult life or middle age and is of more limited value in old age. A systematic program of VA of a representative sample of deaths could assign broad causes not only to deaths in childhood (as has previously been established) but also to deaths in early adult life and middle age.
Oral cancer in southern India: the influence of smoking, drinking, paan-chewing and oral hygiene.
Between 1996 and 1999 we carried out a case-control study in 3 areas in Southern India (Bangalore, Madras and Trivandrum) including 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women), frequency-matched with cases by age and gender. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regressions and adjusted for age, gender, center, education, chewing habit and (men only) smoking and drinking habits. Low educational attainment, occupation as a farmer or manual worker and various indicators of poor oral hygiene were associated with significantly increased risk. An OR of 2.5 (95% CI 1.4-4.4) was found in men for smoking > or = 20 bidi or equivalents versus 0/day. The OR for alcohol drinking was 2.2 (95% CI 1.4-3.3). The OR for paan chewing was more elevated among women (OR 42; 95% CI 24-76) than among men (OR 5.1; 95% CI 3.4-7.8). A similar OR was found among chewers of paan with (OR 6.1 in men and 46 in women) and without tobacco (OR 4.2 in men and 16.4 in women). Among men, 35% of oral cancer is attributable to the combination of smoking and alcohol drinking and 49% to pan-tobacco chewing. Among women, chewing and poor oral hygiene explained 95% of oral cancer.
An Independent Survey to Assess Completeness of Registration: Population Based Cancer Registry, Chennai, India.
Cancer registration in the population based cancer registry (PBCR), Chennai, India, is carried out by active methods. It undertakes re-screening of cases in government hospitals and Cancer Institute (WIA), trace back death certificate notifications and collect information on all the deaths, irrespective of the stated cause on the death certificate, occurring in the registry area routinely to reduce the under-registration of incident cancer cases and associated mortality. The completeness of registration during 1982-95 was assessed by conducting an independent survey in randomly selected areas in Chennai. The total number of households covered in the survey was 7737 and were collected which constituted 1% of the Chennai city population. The response rate to the survey was 96%. A total of 42,502 incident cancer cases were registered in Chennai PBCR during 1982-95. The total number of cancer cases that were already registered in PBCR from the survey area during 1982-95 was 208. Out of 208 cases, 91 (44%) were identified in the survey; the families of the remaining 117 had migrated out of the surveyed area. Two new cancer cases hitherto unregistered in the PBCR during 1982-95 were identified from the survey. Based on the survey, it is estimated that the completeness of cancer registration in Chennai PBCR is 96%, which is comparable to those of other registries in the world.
Grand challenges in global health and the practical prevention program? Asian focus on cancer prevention in females of the developing world.
In response to the request for 'Breakthrough Questions' for 'Grand Challenges in Global Health' recently published in Nature, the Asian Pacific Organization for Cancer Prevention should focus its attention on what projects are of the highest priority for integration with its Practical Prevention Program (PPP). The most common female cancers in most of the countries of Asia are carcinoma of the breast, followed by the uterine cervix. While the incidences of breast adenocarcinomas are still generally lower than in the Western world they are rapidly increasing, and squamous cell carcinomas of the cervix are a major problem. Clearly there are many areas which would reward research. One factor which appears of major relevance in the mammary gland case is the diet, and particularly the phytoestrogens included in 'tofu', along with physical exercise. The age at which these could be operating needs to be elucidated, with reference to timing of menarche and menopause, and also breast mammographic density, another predictor of likelihood of neoplasia. In the cervix, the predominant influence is well established to be persistent infection with a high risk 'oncogenic' type of human papilloma virus (HPV). Vaccines therefore hold much promise, but a better understanding of the mechanisms underlying spontaneous clearance of both infection and cervical intraepithelial neoplasia (CIN) of different grades is also essential for optimal intervention. The roles of smoking and antioxidant intake in particular deserve emphasis. In Asia, with the considerable variation evident in both breast and cervical cancer incidence rates, as well as in cultural and other environmental factors, we are in a very favourable position to meet two specific challenges: 1). elucidation of how diet in adolescence determines susceptibility to neoplasia of the mammary glands; and 2). determination of what governs persistence of HPV infection. Realisation of these pivotal research aims, with especial emphasis on the context of the PPP, is our shared goal.
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.