Role of Vitamin D and its Genetic Polymorphisms in Epstein-Barr Virus Activity and the Risk of Nasopharyngeal Carcinoma

  • Topic:
  • Institution: University of Hong Kong
  • Country: Hong Kong
  • Status: Ongoing

Scientific abstract

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Background

To date, despite several identified important risk factors of nasopharyngeal carcinoma (NPC), the etiology of NPC remained highly controversial. The current knowledge on related genetic, viral and environmental interactions has proved insufficient in answering numerous major questions: Why does NPC remain a rare disease in most of the world despite the fact that Epstein-Barr virus (EBV) infection has ubiquitous prevalence worldwide? Why do only a minority of persons infected with EBV develop NPC? Furthermore, there is limited evidence that the global secular trends of NPC can be explained by a corresponding change in the consumption pattern of salted fish, another important risk factor of NPC. Clearly, there remains a huge knowledge gap in the etiology of NPC. Recently, emerging evidence shows that Vitamin D, which has anti-inflammatory and immuno-modulatory effects, may play an important role in numerous chronic diseases including cancers. Indeed, recent large studies showed an inverse relationship between Vitamin D level and the risk of colorectal cancer. Given the key role of EBV infection in the pathogenesis of NPC, micronutrients with immuno-modulatory effects such as Vitamin D warrants special attention in NPC. Indeed laboratory studies showed that EBV-encoded nuclear protein may interact with vitamin D pathways and impact on EBV viral strategy. Despite much interest in the links between Vitamin D status, EBV activity and the risk of NPC, no such data is currently available. Further research is thus warranted.

Primary Objectives

To study the role of Vitamin D deficiency and its genetic polymorphisms in the risk of NPC.

Secondary Objective

To investigate any diet-gene interactions. 

Setting

This study will build on the existing powerful infrastructure of the Centre for NPC Research (CNPCR) under the Area of Excellence Scheme led by the University of Hong Kong. The CNPCR draws the strengths from 3 universities and 5 key hospitals in Hong Kong, and synergizes complimentary scientific and clinical expertise in NPC research.

Methods

Design

A case-control study (NPC cases n=1000 and hospital controls n=1000) recruited over 30 months (Nov 2011 – May 2014). Nutritional Exposure: Detailed validated questionnaires will be used to assess demographic, dietary and lifestyle factors of subjects using an innovative life course milestone approach. In addition, assessment of early life exposures will be specifically complemented by an add-on questionnaire targeted to the parents of subjects. Vitamin D status will be estimated by both questionnaire-derived data and serum 25-hydroxyvitamin D. Genetic Exposure: Single-nucleotide polymorphisms of vitamin D level will be determined using SEQUENOM. Outcome Phenotypes: Serum biomarkers of EBV activity and tumour histopathologic features.

Study Endpoints

Primary

  1.  Comparison of Vitamin D status between NPC cases and hospital controls
  2.  Relations between vitamin D status and serum/ histpathologic EBV activity
  3.  Relations between Vitamin D-related genetic polymorphisms, clinical status, and serum/ histopathologic EBV viral activity

Secondary

  1. Any diet-gene interactions

Impact

  1.  In line with strategic research directions of the WCRF International, this study will address the important question on the role of Vitamin D deficiency, a global nutritional pandemic, in the risk of NPC and its relation to EBV activity.
  2.  The study utilizes the existing strength of the CNPCR under the Area of Excellence Scheme and further provides a unique strategic platform for further multi-disciplinary NPC research.
  3.  Findings from this study can potentially translate into important prevention strategies. 
  4.  Such a landmark collaboration funded by the WCRF will certainly promote research and prevention synergies between Asia and other leading institutions worldwide.
  5.  Basis for prospective research into the role of vitamin D deficiency in NPC survivors.

Plain language abstract

Background

Infection by a virus named “Epstein-Barr Virus (EBV)”, an infection which is very common worldwide, has been identified as an important factor associated with nasopharyngeal cancer (NPC). Other important factors of NPC included frequent consumption of food items containing a chemical called nitrosamines, e.g. salted fish. Despite these previous findings, the exact cause of NPC still remained unclear: Why does NPC remain a rare disease in most of the world despite the fact that EBV infection is so common worldwide? Why do only a minority of persons infected with EBV develop NPC? Furthermore, there is limited evidence that the global trends of NPC is due to reduced consumption of food items containing nitrosamines e.g. salted fish. Clearly, there remains a huge knowledge gap in the cause of NPC. Recently, emerging evidence shows that Vitamin D, which has anti-inflammatory effects and effects on regulating immune functions, may play an important role in numerous diseases including cancers. Indeed, recent large studies showed an inverse relationship between blood vitamin D levels and the risk of colorectal cancer. Given the importance of EBV infection in causing NPC, nutrient with regulatory effects on the immune system such as Vitamin D may worth special attention. Laboratory studies showed that viral activity of EBV may be affected by Vitamin D, implying a potential protective effect of Vitamin D against EBV infection. However, it is not know whether this relationship may affect one's risk of developing NPC. Further research is thus needed. Therefore, we propose this study with the aim to study the role of Vitamin D deficiency (and genetic variants related to Vitamin D deficiency) in NPC. We also aim to investigate whether these factors, namely genetic variation, lifestyle factors, and dietary factors. may interact and affect one's risk of NPC.

Setting

This study will build on the existing powerful infrastructure of the Centre for NPC Research (CNPCR) under the Area of Excellence Scheme led by the University of Hong Kong. The CNPCR draws the strengths from 3 universities and 5 key hospitals in Hong Kong, and synergizes complimentary scientific and clinical expertise in NPC research.

Methods

The study will recruit 1000 patients with NPC and 1000 controls (without NPC) subjects who were admitted for hospitalization for reasons other than NPC, recruited over 30 months (Nov 2011 – May 2014). Detailed validated questionnaires will be used to assess background characteristics, dietary and lifestyle factors of subjects. In addition, assessment of early life exposures will be complemented by an innovative add-on questionnaire, which will be interview-administered to the parents of subjects for comparison of answers. Vitamin D status will be measured by both questionnaire inquiry and blood measurements. Genetic variants of subjects related to Vitamin D will be measured by blood using high performance, validated technology named SEQUENOM. Blood markers of EBV activity and tumour features will be measured. The final aim of the study is to see whether Vitamin D deficiency is related to NPC and EBV viral activity, and whether Vitamin D-related genetic variants have a role in affecting risk of NPC.

Impact

  1.  In line with strategic research directions of the WCRF International, this study will address the important question on the role of Vitamin D deficiency, a global nutritional problem, in the risk of NPC.
  2. The study utilizes the existing strength of the our research centre under the Area of Excellence Scheme and further provides a unique strategic platform for further multi-disciplinary research.
  3. Findings from this study can potentially translate into important prevention strategies.
  4.  Such a landmark collaboration funded by the WCRF will certainly promote research and prevention synergies between Asia and other leading institutions worldwide.
  5.  Basis for further research to help NPC patients improve their survival.

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