Supannee Promthet

Risk factors for cholangiocarcinoma in high-risk area of Thailand: Role of lifestyle, diet and methylenetetrahydrofolate reductase polymorphisms

BACKGROUND AND AIM Cholangiocarcinoma (CCA) is the most common cancer in Northeast Thailand. Endemicity of Opisthorchis viverrini (OV) - a known carcinogen - is responsible, but although infection is very common, the lifetime risk of CCA is only 5%. Other co-factors must exist, including aspects of lifestyle or diet along with variations in genetic susceptibility to them. Change in methylenetetrahydrofolate reductase (MTHFR) activity may influence both DNA methylation and synthesis. This study investigates risk factors for CCA with a focus on lifestyle, diet and MTHFR polymorphisms. METHODS Nested case-control study within cohort study was conducted. 219 subjects with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and presence/absence of OV eggs in stool. Lifestyle and dietary data were obtained at recruitment. MTHFR polymorphisms were analyzed using PCR with high resolution melting analysis. The associations were assessed using conditional logistic regression. RESULTS Consumption of alcohol, raw freshwater fish and beef sausage increased the risk of CCA, while fruit and/or vegetables consumption reduced risk. There were interactions between MTHFR and preserved freshwater fish and beef. These dietary items are either a source of OV or of pre-formed nitrosamine, folate and antioxidants that are of possible relevance in OV carcinogenesis. CONCLUSIONS Primary prevention of CCA in high-risk population is based upon efforts to reduce OV infection. Reduced consumption of alcohol and preserved meats, and increased consumption of dietary folate, actions with a wider preventive potential, may also help in the reduction of CCA burden.

Risk Factors for Oral Cancer in Northeast Thailand

Oral cancer is a common site of head and neck cancer, and is relatively frequent in Northeast Thailand. The objective of this hospital-based, case-control study was to determine associations with risk factors. A total of 104 oral cancer cases diagnosed between July 2010 and April 2011 in 3 hospitals were matched with control subjects by age, sex and hospital. Data were collected by personal interview. There were significant associations between oral cancer and tobacco smoking (OR=4.47; 95%CI=2.00 to 9.99), alcohol use among women (OR=4.16; 95%CI=1.70 to 10.69), and betel chewing (OR=9.01; 95%CI=3.83 to 21.22), and all three showed dose-response effects. Smoking is rare among Thai women (none of the control women were smokers), but betel chewing, especially among older women, is relatively common. We did not find any association between practicing oral sex and oral cancer.

Risk Factors for Colon Cancer in Northeastern Thailand : Interaction of MTHFR Codon 677 and 1298 Genotypes with Environmental Factors

Background Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand. Methods This hospital-based case–control study was conducted during 2002–2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression. Results Increased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed ≤0.50 or >0.50 units of alcohol per day had elevated risks (ORadj = 3.5; 95% CI: 1.19–10.25 and ORadj = 1.71; 95% CI: 0.74–3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18–62.79) and occasional constipation (3.43; 1.72–6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively). Conclusions In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.

Infection with Opisthorchis viverrini and Use of Praziquantel among a Working-age Population in Northeast Thailand

Infection with Opisthorchis viverrini (OV) due to eating certain traditional freshwater fish dishes is the principal risk factor for cholangiocarcinoma in Northeast Thailand where the infection is endemic and the incidence of this form of primary liver cancer has been the highest in the world. This paper is the second report of a prospective research project to monitor the impacts of a national liver fluke control programme in a rural community of Northeast Thailand. A sample of 684 villagers aged 20-65 years completed an interview questionnaire and were tested for infection using the Kato thick smear technique. The questionnaire was designed for the exploration of associations between OV infection, previous treatment with praziquantel, and knowledge and beliefs about the drug. The data were analysed using descriptive statistics and multiple logistic regression. The overall prevalence of OV infection was 37.2% and was highest in the 20-35 year age group, in those with a university degree and in those employed in the government sector. As many as 91.8% reported eating fish dishes known to place them at risk of infection. In the multiple regression analysis, previous use of praziquantel and lack of knowledge about whether or not the drug has a protective effect against re-infection were the only factors related to OV infection (ORadj= 2.31, 95%CI =1.40-3.79 and ORadj= 1.95, 95%CI= 1.24-3.05). The findings were discussed in terms of the possibly unwise dependency on praziquantel as a primary element in a control programme.

Survival of Cholangiocarcinoma Patients in Northeastern Thailand after Supportive Treatment

BACKGROUND Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. OBJECTIVE This study aimed to assess the survival rates of CCA patients after supportive treatment. METHODS A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. RESULTS The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). CONCLUSION It is very important to encourage patients to see health personnel at an early stage.

Prevalence and Risk Factors for Opisthorchis viverrini Infections in Upper Northeast Thailand

Opisthorchis viverrini is an ongoing public health problem in Northeast Thailand. Despite continuous efforts for decades by healthcare organizations to overcome this problem, infection rates remain high. To enable related personnel to identify and address the various issues effectively, a cross-sectional study was performed to investigate prevalence and risk factors for opisthorchiasis. The target group was 3,916 Thai residents of Northeast Thailand who were 15 or over. Participants were recruited using the 30 clusters sampling technique. The data were gathered through questionnaires, focus group discussions, in-depth interviews, and stool examinations for parasite eggs (using the Modified Kato Katz method). The data were analyzed using descriptive and inference statistics; in order to ascertain the risk factors and test them using the odds ratio and multiple logistic regressions. The prevalence of opisthorchiasis was 22.7% (95%CI: 0.26 to 0.24). The province with the highest prevalence was Nakhorn Phanom (40.9%; female to male ratio =1:1.2). The age group with the highest prevalence was 40-49 year olds. All age groups had a prevalence >20%. Four of seven provinces had a prevalence >20%. The factors related to opisthorchiasis were (a) sex, (b) age (especially > 50), (c) proximity and duration living near a water body, and (d) eating raw and/or fermented fish. In order to reduce the prevalence of opisthorchiasis, the focus in populations living in upper Northeast Thailand should be changing their eating behaviors as appropriate to their tradition and context.

Risk Factors for Cholangiocarcinoma in the Lower Part of Northeast Thailand: a Hospital-based Case-control Study

BACKGROUND Cholangiocarcinoma (CCA) is the most common cancer in Northeast Thailand. It is also a crucial health problem for Thai people. Various risk factors for CCA have been identified in the upper part of Northeast Thailand, but no similar studies of risk factors have been conducted in the lower parts of the region. This study aimed to investigate factors associated with CCA in the resident population. MATERIALS AND METHODS A hospital-based case-control study was conducted during 2009-2012 with the recruitment of 123 CCA cases and 123 non-CCA patient controls, matched for sex, age and residential area. Information was collected by interview with a structured questionnaire. Blood samples were collected for assays of anti-OV antibodies. Associations between various personal factors, dietary habits, family history, the presence of anti-OV antibodies and CCA were analyzed using multiple conditional logistic regression. RESULTS Patients who consumed raw meat (beef, pork) and alcoholic beverages ≥3 times per week had a higher risk of CCA than non-consumers (ORadj=4.33; 95%CI=1.14-16.35 and ORadj=2.13; 95%CI=1.00-4.55, respectively). Patients who had a family history of cancer had a higher risk than those who did not (ORadj=4.34; 95%CI=1.80-10.43). Also, patients who had anti-OV antibodies (AU>23.337) had a higher risk than those whose anti-OV antibodies were below the cut-off (AU≤23.34) (ORadj=3.09; 95%CI=1.04-9.16). CONCLUSIONS As is the case in the upper part of Northeast Thailand, OV infection is a crucial risk factor for CCA in people who live in lower part of the region. Similarly, a family history of cancer and the consumption of alcohol are risk factors for CCA.

Association of Epstein-Barr virus infection with oral squamous cell carcinoma in a case–control study

BACKGROUND Besides the well-known risk factors, Epstein-Barr virus (EBV) might play a significant role in oral squamous cell carcinoma (OSCC). To explore the role of EBV in OSCC, the prevalence of EBV infection in oral exfoliated cells of OSCC cases and controls in northeastern Thailand was investigated, and the association of EBV in tumor lesion cells was further confirmed. METHODS Oral exfoliated cells were collected from OSCC cases and non-cancer controls. Cells from tumor lesions were taken from OSCC patients for further strong confirmation of the association of EBV with OSCC. EBV DNA was detected by polymerase chain reaction (PCR) using primers specific for EBV DNA polymerase. The EBV DNA positive samples were confirmed further by nested PCR. RESULTS Epstein-Barr virus was detected in the oral exfoliated cells of 45.05% of OSCC patients and 18.08% of the non-cancer control (P < 0.001). Similarly, EBV was detected in 32.5% of the tumor lesions. Betel quid chewing was statistically significantly associated with EBV prevalence (OR = 2.08), whereas no association with tobacco smoking and alcohol consumption. Alcohol consumption and betel quid chewing were significantly associated with OSCC (OR = 3.05 and OR = 5.05, respectively), but tobacco smoking was not associated. Interestingly, EBV was significantly associated with OSCC (OR = 3.76). CONCLUSIONS Epstein-Barr virus prevalence is associated with OSCC and seems to be enhanced by betel quid chewing, suggesting that EBV may, together with betel quid chewing, act as an important etiological risk factor of OSCC.

Development of a Community-Based Approach to Opisthorchiasis Control

A liver fluke, Opisthorchis viverrrini (OV), is the major cause of the high incidence of cholangiocarcinoma in North-eastern Thailand. The prevalence of OV infection remains high in various parts of the country, especially in wetland rural areas where a large proportion of the community work in agriculture and continue the traditional practice of eating raw or uncooked cyprinoid fish products. The national control program seems to have had little impact in many of these areas, and it has been difficult to make precise assessments of the overall effectiveness of the program. Therefore there is a need for a community-based approach to prevent infection with the parasite, ideally involving as many players as possible. Here we document an attempt to assess the best means to prevention on the basis of a community intervention in three villages in north-east Thailand, with participation of representatives of Health Promotion Hospitals of the Ministry of Public Health with dedicated staff, but also school teachers, independent government sponsored village health volunteers, and housewives responsible for cooking and diet selection. An action plan was followed, allowing detailed discussions of practical proposals, their introduction and then repeated reflection and further proposals at the individual village level.

Reproductive Risk Factors for Thyroid Cancer: A Prospective Cohort Study in Khon Kaen, Thailand

BACKGROUND Because of the gender disparity in the incidence of thyroid cancer, this study aimed to determine the association between reproductive factors and thyroid cancer. METHODS A total of 10,767 eligible women from the Khon Kaen Cohort, recruited and interviewed between 1990 and 2001, were followed up until 2011. The data were linked to the Khon Kaen Population-Based Cancer Registry to detect thyroid cancer cases. RESULTS There was 17 thyroid cancer cases detected, an incidence of 11.2 per 100,000 person-years, of which 70.6 % were papillary tumors. The incidence was apparently greater among those with an early age of menarche, nulligravida women, and oral contraceptive users. CONCLUSIONS There was a trend for thyroid cancer to develop in relation to longer estrogen exposure. This evidence is inconclusive but warrants further investigation.