Infection with Opisthorchis viverrini (OV) is associated with cholangiocarcinoma. OV is common in northeast Thailand, but less than 10% of the inhabitants develop cholangiocarcinoma. Animal experiments suggest that OV infection alone does not cause cholangiocarcinoma, and thus other environmental and genetic factors may play a role in causation. We conducted a population-based case-control study in which sex, age and place of residence were matched individually. Polymorphisms of GSTM1 and GSTT1 alone were not associated with risk for cholangiocarcinoma, while an elevated level of antibodies against OV (ELISA) 0.200 was the strongest risk indicator (odds ratio as compared to that <0. Key words: population-based case-control study; inflammation; polymorphism; alcohol drinking; nitrosamine Cholangiocarcinoma is uncommon, and the aetiology has been elucidated only for a limited portion of cases.1 Northeast Thailand has an exceptionally high incidence of liver cancer of up to 87.5 (male) and 37.2 (female) per 100,000 (world population-adjusted incidence rate). Most of these cases have been attributed to cholangiocarcinoma.2 Infestation of the liver fluke, Opisthorchis viverrini (OV), has been causally related to cholangiocarcinoma in this region. 3 The prevalence of OV infection in Nakhon Phanom province was between 30 and 70% with substantial variation between villages; 4 the technique for estimation of prevalence was not explicitly mentioned but supposed OV egg counting in the faeces. However, it is unknown why only a limited proportion of the inhabitants (<10%) develop cholangiocarcinoma.In our study, we hypothesised that genetic background may be a contributing factor in the occurrence of the cholangiocarcinoma. Hence, we examined the association between polymorphisms of genes for glutathione-S-transferase enzymes, GSTM1 and GSTT1, and the risk for cholangiocarcinoma. Because both enzymes function in carcinogen detoxification systems, 5 it seems reasonable to speculate that null variants of these genes may be associated with increased risk of cancer. 6The association between OV infection and cancer risk has been a common assumption, but adequate analytic epidemiological studies are sparse. Parkin and colleagues 7 reported in their casecontrol study that past or present infection with OV, as indicated by serum antibodies against OV, is associated with a 5-fold increase in cancer risk. Although the anti-OV antigen titre was elevated and reached a plateau at an approximately 2 months after OV inoculation in hamsters, 8 the transition of the antibody level over the lifespan remains uncertain in both humans and animals. We thus examined the risk of foods possibly containing OV metacercariae as well as that of OV infection as indicated by serum antibody response.In animal experiments, OV infection causes cholangiocarcinoma with coadministration of nitrosamine 9 in a dose-dependent manner.10 Diet and cigarette smoking are major sources of nitrosamine exposure, 11 and several foods and foodstuffs consumed in the study ar...
With careful patient selection, radical resection for gallbladder cancer improves the prognosis with acceptable operative mortality and morbidity rates, even for stage IV disease, provided that complete gross tumour resection is combined with radiotherapy.
Human invariant Vα24+ NKT cells are a relatively new subpopulation of lymphocytes. It has been reported that Vα24 NKT cells are significantly involved in some human diseases. We have evaluated the number and function of Vα24 NKT cells in both healthy volunteers and cancer patients. In this study we found that Vα24 NKT cells in unfractionated PBMCs obtained from cancer patients did not respond efficiently to α-galactosylceramide (α-GalCer) in vitro. Thus, their proportion after stimulation with α-GalCer was smaller than that found in healthy volunteers. However, the cancer patients’ Vα24 NKT cells retained cytotoxic activity against malignant target cells, and they could efficiently proliferate to α-GalCer when fractionated by sorting. Furthermore, we found that addition of G-CSF to the culture could restore the low proliferative response of Vα24 NKT cells from cancer patients. These results suggest that some functions of NKT cells in cancer patients are impaired, and this observation carries significant implications for immunotherapy-based cancer treatments.
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