Nopparat Songserm

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 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.

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.

Prevalence and Co-infection of Intestinal Parasites among Thai Rural Residents at High-risk of Developing Cholangiocarcinoma: A Cross-sectional Study in a Prospective Cohort Study

Intestinal parasitic infections (IPIs) are still important to the health of Thai rural residents. IPIs are the cause of many chronic diseases with, for example, opisthorchiasis resulting in progression to cholangiocarcinoma (CCA). This cross-sectional study in a prospective cohort study aimed to examine the prevalence and co- infection of intestinal parasites among Northeastern Thai rural residents, recruited into the Khon Kaen Cohort Study (KKCS), and who were residing in areas of high-risk for developing CCA. On recruitment, subjects had completed questionnaires and provided fecal samples for IPI testing using the formalin ethyl acetate concentration technique. Data on selected general characteristics and the results of the fecal tests were analysed. IPI test results were available for 18,900 of cohort subjects, and 38.50% were found to be positive for one or more types of intestinal parasite. The prevalence of Opisthorchis viverrini (O. viverrini) infection was the highest (45.7%), followed by intestinal flukes (31.9%), intestinal nematodes (17.7%), intestinal protozoa (3.02%), and intestinal cestodes (1.69%). The pattern of different infections was similar in all age groups. According to a mapping analysis, a higher CCA burden was correlated with a higher prevalence of O. viverrini and intestinal flukes and a greater intensity of O. viverrini. Both prevention and control programs against liver fluke and other intestinal parasites are needed and should be delivered simultaneously. We can anticipate that the design of future control and prevention programmes will accommodate a more community-orientated and participatory approach.

Factors affecting survival time of cholangiocarcinoma patients: a prospective study in Northeast Thailand.

Cholangiocarcinoma (CCA) is a major health problem and cause of death among people in Northeastern Thailand. In this prospective study 171 patients newly diagnosed with CCA by physicians in 5 tertiary hospitals in four provinces of northeastern of Thailand between February and July 2011 were followed up to January 2012. The outcome was survival time from diagnosis to death. A total of 758.4 person-months of follow-up were available. The mortality rate was 16.9 per 100 person-months (95%CI: 14.1-20.1). The median survival time among CCA patients was 4.3 months (95%CI: 3.3-5.1). Coxs proportional hazard model was used to study the independent effects of factors affecting survival time among patients. Statistically significant factors included advanced stage at diagnosis (HR: 2.5, 95%CI: 1.7-3.8), presentation with jaundice (HR: 1.7, 95%CI: 1.1-2.4) or ascites (HR: 2.8, 95%CI: 1.8-4.4), and positive serum carcinoembryonic antigen (HR: 2.3, 95%CI: 1.2-4.3). Patients who had received standard treatment had a better prognosis that those who did not (HR: 0.5, 95%CI: 0.3-0.7).

XRCC1 gene polymorphism, diet and risk of colorectal cancer in Thailand.

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide. This study aimed to investigate the interaction between the presence of a polymorphism of the XRCC1 gene and known risk factors for colorectal cancer in Thailand. MATERIALS AND METHODS A hospital-based case-control study was conducted in Thailand. The participants were 230 histologically confirmed new cases and 230 controls matched by sex and age and recruited from the same hospital. Information about demographic characteristics, life style, and dietary habits was collected using structured interviews, and blood samples were taken which were used for the detection of a homozygous and heterozygous polymorphisms of XRCC1. Associations were assessed using multiple conditional logistic regression. RESULTS In the univariate analysis, factors found to be significantly associated with an increased risk for CRC were the presence of the XRCC1 AA homozygote (OR= 4.95; 95% CI: 1.99-12.3), a first degree family history of cancer (OR= 1.74; 95% CI: 1.18-2.58), and a high frequency of pork consumption (OR= 1.49; 95% CI: 1.00-2.21). Intakes of fish fruit and vegetables appeared to be protective factors, but the associations were not statistically significant. In the multivariate analysis only the XRCC1 AA homozygote polymorphism and a family history of cancer emerged as risk factors (OR= 4.96; 95% CI: 1.90- 12.95 and OR=1.80; 95% CI: 1.18-2.72, respectively). CONCLUSIONS While the XRCC1 AA homozygote and a family history of cancer were found to be associated with an increased risk of CRC, none of the dietary intake variables were clearly identified as risk or protective factors. There is a need for further research to determine the reasons for this.

Community Participation in Cholangiocarcinoma Prevention in Ubon Ratchathani, Thailand: Relations with Age and Health Behavior.

A high prevalence of Opisthorchis viverrini infection is usually found in wetland geographical areas of Thailand where people have traditional behavior of eating uncooked freshwater fish dishes which results in cholangiocarcinoma (CCA) development. There were several approaches for reducing opisthorchiasis-linked CCA, but the prevalence remains high. To develop community participation as a suitable model for CCA prevention is, firstly, to know what factors are related. We therefore aimed to investigate factors associated with the community participation in CCA prevention among rural residents in wetland areas of Ubon Ratchathani, Thailand. This was a cross-sectional analytic study. All participants were 30-69 years of age, and only one member per house was invited to participate. A total of 906 participants were interviewed and asked to complete questionnaires. Independent variables were socio-demographic parameters, knowledge, health belief and behavior to prevent CCA. The dependent variable was community participation for CCA prevention. Descriptive statistics were computed as number, percentage, mean and standard deviation. Associations were assessed using logistic regression analysis with a P-value <0.05 considered statistically significant. Of all the participants, more than 60% had regularly participated in activities to prevent CCA following health officials advice. Age and health behavior to prevent CCA were factors associated with community participation for CCA (p<0.001). Both factors will be taken into consideration for community participation approaches for CCA prevention through participatory action research (PAR) in future studies.

Gene-environment interaction involved in cholangiocarcinoma in the Thai population: polymorphisms of DNA repair genes, smoking and use of alcohol.

Objective Cholangiocarcinoma (CCA) is the most common malignancy in a Northeast Thai population. Smoking and alcohol drinking are associated with the production of free radical intermediates, which can cause several types of DNA lesions. Reduced repair of these DNA lesions would constitute an important risk factor for cancer development. We therefore examined whether polymorphisms in DNA base-excision repair (BER) genes, XRCC1 G399A and OGG1 C326G, were associated with CCA risk and whether they modified the effect of smoking and alcohol drinking in the Thai population. Design A nested case–control study within the cohort study was conducted: 219 participants with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and the presence/absence of Opisthorchis viverrini eggs in stools. Smoking and alcohol consumption were assessed on recruitment. Polymorphisms in BER genes were analysed using a PCR with high-resolution melting analysis. The associations were assessed using conditional logistic regression. Results Our results suggest that, in the Thai population, polymorphisms in XRCC1 and OGG1 genes, particularly in combination, are associated with increased susceptibility to CCA, and that their role as modifiers of the effect of smoking and alcohol consumption influences the risk of CCA. Conclusions Better ways of reducing habitual smoking and alcohol consumption, targeted towards subgroups which are genetically susceptible, are recommended. CCA is a multifactorial disease, and a comprehensive approach is needed for its effective prevention. This approach would also have the additional advantage of reducing the onset of other cancers.

Risk Factors for Rectal Cancer and Methylenetetrahydrofolate Reductase Polymorphisms in a Population in Northeast Thailand

BACKGROUND AND AIM Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to be associated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors, family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possible interactions with lifestyle factors in Northeast Thailand. METHODS A hospital-based case-control study was conducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls. Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFR C677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s. rectal cancer risk were assessed using logistic regression analysis. RESULTS Subjects with frequent and occasional constipation had a higher risk (OR adj.=14.64; 95%CI=4.28-50.04 and OR adj.=2.15; 95%CI=1.14-4.06), along with those who reported ever having hemorrhoids (OR adj.=2.82; 95%CI=1.36-5.84) or a family history of cancer (OR adj.=1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk (OR adj.=1.82; 95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. CONCLUSIONS This study suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having had hemorrhoids, a family history of cancer and pork consumption.

Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand.

In northeast Thailand, cholangiocarcinoma (CCA) is a major cause of mortality. Patients with CCA have a poor prognosis and short-term survival. The purpose of this study was to investigate the association between health-related quality of life (HRQOL) and survival time, and to explore whether change in HRQOL score is related to survival among CCA patients. The study was performed between February 2011 and January 2012, and included 171 patients with newly diagnosed CCA from 5 tertiary hospitals in four provinces of northeast Thailand. The HRQOL was measured at baseline, 1 month, and 2 months after diagnosis by the FACT-Hep questionnaire (Thai version 4). The outcome was survival time from diagnosis. Cox’s proportional hazard model was used to evaluate the association between HRQOL and survival time. A higher overall score on HRQOL was associated with a significantly better survival (HR per 5 units increase in HRQOL was 0.92, 95% CI: 0.88–0.96). Two of the separate domains contributing to the overall HRQOL—functional well-being and hepatobiliary cancer subscale—were found to have independent effects on survival, even after adjustment for potential confounding variables, and the other domains of HRQOL. CCA patient whose HRQOL scores had improved (≥9 units) at the 1st month of follow up had a reduced probability of dying from the disease (HR: 0.56, 0.32–0.95) after adjustment for the same confounding factors. A positive association between HRQOL at diagnosis and survival time was found. An improvement in HRQOL score in the first months after diagnosis further increases survival.