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Background: Smokeless tobacco (SLT) use is a major public health burden and highly prevalent in Bangladesh. Over 20 million Bangladeshi adults are currently using SLT. Bangladesh Government had announced its vision to become a tobacco free country by 2040. Therefore, public health efforts focusing on preventing SLT onset among adolescents would contribute towards this vision. However, apart from national adolescent SLT prevalence from Global youth Tobacco Survey (GYTS), no other information linked to adolescent SLT use is available to inform future interventions. Also, SLT use related health burden such as oral cancer is highly prevalent in Bangladesh. Globally, Bangladesh ranked third for oral cancer related death. Every year over 8,000 Bangladeshi adults lost their lives because of this deadly disease. Regarding the relationship between SLT and oral cancer risk, there is a disconnection between the study findings from the western countries and developing countries. With the diversity of SLT products and its content there is a need to produce local evidence. Therefore, the overall aim of this PhD research was to examine the factors contributing to adolescent SLT use in Bangladesh and the role of SLT in oral carcinogenesis among Bangladeshi adults. Methods: To attain the study objectives, in 2015 a cross-sectional survey (n=790, response rate 100%) in two rural secondary schools and a hospital-based case-control study (n=507; case:169 and controls: 338, case participation rate 92.86%) were carried out in Bangladesh. Results: The findings of the adolescent cross-sectional survey suggest that the ever and current SLT prevalence among rural Bangladeshi adolescent was 9.5% (75) and 3.7% (29) respectively. Males were the leading users of SLT. Zarda (80%) is the most common type of SLT used by the adolescents. Rural Bangladeshi adolescent started using SLT as early as seven years old and younger. Social sources (41.4%) were the most common source of SLT reported. Most adolescents (65.2%) were able to buy SLT from commercial stores without any restrictions. Many current SLT users (89.7%) wanted to quit SLT but professional help was not available. Overall, adolescents had good knowledge about the adverse effects of SLT use, though misconceptions about the addictive nature of SLT use were prevalent. Older age, self-efficacy, perceived barriers, perceived benefits and perceived severity were the significant predictors of adolescent SLT use. The findings of the hospital-based case-control study suggest a strong association between SLT use and oral cancer risk among Bangladeshi adults. Women [OR: 14.33 (95%CI: 6.33-32.42)] had the higher risk of developing oral cancer than men [OR: 5.29 (95%CI: 2.62-10.67)] from SLT use. Among men highest risk was observed among dual users (SLT and smoking) [OR: 17.23 (95%CI: 5.70-52.01)]. Both Betel Quid (BQ) with and without tobacco increased the oral cancer risk. However, the risk was lower for chewing BQ without tobacco than BQ with tobacco. The risk of oral cancer increased with the increasing frequency and intensity of SLT use. About 61% of all oral cancer cases in Bangladesh were attributable to SLT use. Among other oral cancer risk factors - bidi smoking, oral hygiene factors and leanness were associated with increased oral cancer risk. Conclusion: The findings of the present cross-sectional survey and hospital-based case-control study were comparable to existing literatures. Our evidence suggests that SLT use among rural Bangladeshi adolescent is low compared to other neighbouring countries. However, initiation of SLT at an early age is a public health concern. Lack of professional help to quit SLT and poor implementation of tobacco control laws were prevalent. Overall knowledge about SLT use and its ill effects was good, but misconceptions were prevalent. The case-control study demonstrated a significant increase of risk of oral cancer is associated with SLT use. Women had higher risk of developing oral cancer of SLT use than men. For men dual use of SLT and smoking was the major risk factor. Both BQ with and without tobacco was associated with oral cancer incidence. A large number of oral cancer cases in Bangladesh is preventable by tackling the SLT epidemic.

It is estimated that over 30 million people are exposed to arsenic from drinking contaminated groundwater in Bangladesh. Furthermore, due to the use of contaminated water for irrigation purposes, arsenic and other toxic elements are entering the food chain of Bangladeshis. In this thesis, the total levels of toxic elements (As, Cd, Pb) and essential elements (Mn, Se, Zn) in 1,120 samples of Bangladeshi foods (including rice, vegetables, fish) and non-foods (betel quid and baked clay) imported into the United Kingdom were determined. From this analysis, it is concluded that Bangladeshis are exposed to high levels of toxic elements. Inorganic arsenic levels in Bangladeshi rice can be very high, especially from regions with high arsenic in groundwater. However, there is a lack of studies in the literature regarding arsenic levels in rice from regions in Bangladesh with relatively low levels of arsenic in the groundwater. Therefore, rice from one such region (Sylhet district) was analysed. The results indicated that boro (mean 71.7 µg/kg) and aman (mean 85.7 µg/kg) rice from Sylhet contained between 2 to 4-fold lower levels of arsenic, compared to other regions of Bangladesh thus far reported in the literature. Arsenic speciation was carried out on a selection of rice (aromatic and non-aromatic) from Sylhet region and this revealed 70% (mean value) as inorganic arsenic (AsIII and AsV), which is similar to rice grown in other regions of Bangladesh. Importantly, it was found that the arsenic levels of aromatic rice (mean 48.5 µg/kg) from Sylhet region was over 40% lower than that of non-aromatic rice (mean 81 µg/kg). The aromatic rice also contained higher levels of essential elements (such as Se and Zn). It was calculated that for an individual consuming 0.5 kg of rice per day, switching from consumption of non-aromatic rice to aromatic rice would increase Se and Zn intake by 46% and 23% respectively. Arsenic speciation was also carried out on other Bangladeshi food and non-food items, including fish, betel quid and baked clay, to obtain a better insight into exposure to toxic arsenic species. High levels of arsenic (range 3.8-13.1 mg/kg) and lead (range 21-26.7 mg/kg) were detected in the baked clay samples, which are consumed by some Bangladeshi women in an ancient practice known as geophagy. The efficiency of arsenic extraction from baked clay was 33% of the total arsenic present and the main arsenic species present was inorganic AsV (100%); AsIII was not detected in these samples. Millions of Bangladeshis chew betel quid and this contained predominantly AsIII species (extraction efficiency was 100%). Arsenic and lead intake from eating baked clay could exceed the provisional maximum tolerable daily intake (PMTDI) by 2- and 5-fold respectively. For the first time, arsenic speciation in Bangladeshi fish is reported. Hilsha, which is a very popular fish in Bangladesh, contained 2.55 mg/day (mean value) of total arsenic. Extraction efficiencies (%) were 59 – 89 for fish flesh, over 69% of arsenic present in the extract was dimethyl arsenic acid (DMA) species with about 11% arsenobetaine (AsBet) and 19% arsenosugar. These studies reveal that rice, betel quids and baked clay can be a significant source of exposure to inorganic arsenic and DMA in Bangladeshis. Exposure to cadmium is linked with kidney disease and over 20 million people in Bangladesh suffer from chronic kidney disease. Results obtained showed that the daily intake of cadmium by the Bangladeshi population from baked clay (mean 17 µg/day), rice (mean 18.6 µg/day) and certain leafy vegetables (mean 12 µg/day) was higher total daily intake compared to other countries. Surprisingly, puffed rice, which is commonly consumed by Bangladeshis, contained much higher levels of cadmium (mean 67.9 µg/kg) and lead (mean 98 µg/kg), compared to uncooked rice (cadmium, 37.2 µg/kg; lead, 18.9 µg/kg). This may be related to the illegal practice of using urea for whitening puffed rice in Bangladesh. Exposure to manganese in the Bangladeshi population through drinking water has been previously highlighted as a possible health problem, although the intake from foods and non-food has not been reported. The daily manganese intake by Bangladeshis was calculated to be 20.3 mg/day, which is higher than any other country in the world thus far reported. Betel quid components have high levels of manganese and this was reflected by higher urinary manganese the mean urinary Mn levels in chewers (1.93 µg/L, SD 1.8) was significantly higher (3.1 fold; P = 0.009) compared to non-chewers (0.62 µg/L, SD 0.4). Bangladeshi women who eat baked clay and chew betel quids are likely to be exposed to high levels of arsenic, lead and other toxic elements. This is particularly of concern for pregnant women as these metals can be transferred to the unborn baby through the placenta. For assessing the risk of exposure to toxic elements versus intake of essential elements from the same foods, a Food Toxicity Scale (FTS) was devised in order to identify foods that are beneficial or harmful. FTS values were obtained by calculating the toxic elements : essential elements ratio (As:Se, As:Zn etc) and the value obtained subsequently multiplied by toxic element concentration and the quantity of the particular food consumed per day. The higher the FTS value, the greater the risk of exposure to harmful elements. Rice and leafy vegetables had the highest FTS values, partly because large quantities of these foods are consumed. However, lentils and animal products (such as small fish) had relatively lower FTS values compared to other foods. Total daily intake of arsenic (306 µg/day), selenium (90.4 µg/day), cadmium (34.6 µg/day), lead (74.4 µg/day), manganese (20.3 mg/day) and zinc (11.2 mg/day) in the Bangladeshi population was calculated. The intake of arsenic and manganese exceeds the PMTDI for these elements. Water was the highest source of arsenic exposure in Bangladeshis followed by rice. For cadmium and lead, rice and leafy vegetables were the key contributors to the daily intake. The results presented in this thesis show that Bangladeshis are exposed to high levels of toxic elements and how modifications can be made to their diet to not only reduce their exposure to toxic elements but also increase the intake of essential elements. This could be achieved by a combination of the following: (i) reducing the intake of rice (by about 50%); (ii) switching to eating aromatic rice; (iii) increasing the intake of animal products (meat, fish etc.); (iv) decreasing the intake of certain leafy vegetables; and (v) stopping or reducing the practice of eating baked clay and chewing betel quid.