Grant title
Role of vitamin D and its genetic polymorphisms in Epstein-Barr virus activity and the risk of nasopharyngeal carcinoma
Background
A virus named Epstein-Barr (EBV), an infection which is very common worldwide, has been identified as an important factor associated with nasopharyngeal cancer (NPC). Another important risk factor of NPC includes frequent consumption of food items containing chemicals called nitrosamines, eg salted fish.
Despite these previous findings, the exact cause of NPC remains 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 people infected with EBV develop NPC?
Furthermore, there is limited evidence that the global trends of NPC are due to reduced consumption of food items containing nitrosamines eg 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. 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 known whether this relationship may affect one’s risk of developing NPC.
Hypothesis and objectives
Our objective was to study the role of vitamin D deficiency and its genetic polymorphisms on the risk of NPC, as well as investigate any diet-gene interactions.
How the study was carried out
The study recruited patients with NPC and controls (patients without NPC) from five major regional hospitals in Hong Kong. A validated computer-assisted, self-administered questionnaire was used to measure the indicators of vitamin D status (exposure to sunlight, skin tone and dietary vitamin D intake) and other factors. Blood samples were collected and EBV activity, vitamin D status and genetic variants related to vitamin D were measured.
In addition, the link between NPC and tobacco smoking was further examined through analysing existing data from large cohort studies. The correlations between milk consumption and NPC in 48 countries/regions, and salted fish consumption and NPC across eight regions, were investigated with comprehensive cancer and food statistics data.
Conclusions
The results supported our hypothesis that vitamin D deficiency (<37.5 nmol/L) is associated with an increased risk of NPC. Three genetic variants (rs12794714, rs4588 and rs1155563) that were associated with lower vitamin D level were also associated with a higher risk of NPC. These hypothesis-generating findings warrant confirmation in long-term mega prospective cohort collaborative studies and randomised controlled trials.
If true, these findings would have important implications for the prevention of NPC. Salted fish consumption and smoking were also associated with an increased risk of NPC. Milk consumption across different life periods was associated with lower risks of NPC.
Grant publications
- Secular trends of salted fish consumption and nasopharyngeal carcinoma: a multi-jurisdiction ecological study in eight regions from three continents
- Vertically transmitted nasopharyngeal infection of the human papillomavirus: Does it play an aetiological role in nasopharyngeal cancer?
- The battle against nasopharyngeal cancer
- Smoking and nasopharyngeal carcinoma mortality: a cohort study of 101,823 adults in Guangzhou, China
- Milk consumption in relation to incidence of nasopharyngeal carcinoma in 48 countries/regions