Final Report Summary - SOGVID (Survival in Oesophageal and Gastric Cancer Patients and Vitamin D)
The vital importance of vitamin D for bone health is well known, but studies suggest that vitamin D deficiency may also be linked to cancer occurrence and survival. Many well-designed studies have reported worse survival rates in bowel, lung or breast cancer patients with poor vitamin D status, but no well-designed study examined the link between vitamin D and survival of oesophageal or gastric cancer. Research into improving survival in these types of cancer is particularly important because oesophageal and gastric cancer have extremely poor prognoses. Additionally, the incidence of oesophageal cancer has been increasing in some Western regions making these questions more pertinent.
We first sought to summarise all available evidence in relation to vitamin D and risk of oesophageal cancer. No consistent associations were observed between vitamin D exposures and occurrence of oesophageal lesions: based on published literature, we found that better vitamin D status was associated with increased risk of oesophageal cancer. In contrast, no association was observed between dietary vitamin D intake and risk of cancer overall. However, discordant results were observed for two oesophageal cancer subtypes: a non-significantly decreased risk for squamous cell carcinoma were observed, and a non-significantly increased risk for adenocarcinoma; but a decreased risk of adenocarcinoma with higher UVB exposure was reported.
We used UK Biobank, a large cohort study of 500,000 participants to investigate the relationship between vitamin D and upper gastrointestinal cancer risk. Unfortunately, vitamin D concentration in the blood was not available for these participants. Because sunshine-induced vitamin D synthesis in skin is the key source of vitamin D for most humans, we used ambient UVB radiation at the place of residence as a marker of vitamin D status. We found a strong inverse association between annual ambient UVB and odds of developing oesophageal or gastric cancer: after adjustment for important confounders risk of these cancers was 36% reduced among those in the highest tertile of annual UVB, when compared to those with the lowest. The association was strengthened when restricted to oesophageal cancer (risk reduction: 40%), and oesophageal adenocarcinoma cases (risk reduction: 52%). In conclusion, ambient UVB radiation is inversely associated with the development of oesophageal and gastric cancer, even in Ireland, a high-latitude country.
Next, we have successfully assembled one of the largest cohorts of upper gastrointestinal cancer patients for investigation of the role of vitamin D in their survival. Concentration of 25-hydroxyvitamin D (25OHD, the best marker of vitamin D status) was measured. Our results suggest similar inconsistencies that have been previously found: for example, better vitamin D status was linked with survival in gastric cancer patients, but inverse relationship was observed for oesophageal adenocarcinoma. Overall, no firm conclusions could be made and even larger studies are needed.
We hypothesised that weight loss may be a key confounder in the study: vitamin D is released from the fat tissue following weight loss, and consequentially the concentration of 25OHD in the circulation increases. Because weight loss is common in upper gastrointestinal cancers, particularly in a more advanced disease, it might mean that vitamin D concentration acts as a marker of weight loss, which is in turn a marker of disease severity and prognosis. Hence, we investigated the modificatory role of weight loss in the relationship between vitamin D status and survival. While only suggestive associations were found, these taken together with a strong prior expectation due to the well-established link between weight loss and 25(OH)D, warrant further investigation and consideration when examining health outcomes associated with weight loss.
Finally, previous studies linked expression of VDR and CHD1 with survival in oesophageal cancer. We examined expression of CDH1 and VDR in tumour samples from 65 oesophageal cancer cases, and their relationship with cancer survival was explored. There was a significant positive association found when examining the relationship between CDH1 and survival: those with high expression of CDH1 were found to have a 54% reduced risk of mortality compared to those with low expression. Similarly, higher VDR expression was also found to be associated with a reduced risk of mortality and mortality reduction of 60% was found among those with high expression.
Taken together, these results suggest a potential beneficial role of vitamin D in upper gastrointestinal cancer. Further studies are needed to establish whether these associations are causal. Should beneficial effects of vitamin D be shown, there are no obstacles preventing the translation to clinical practice, since vitamin D is safe, inexpensive and readily available in the form of supplements and fortified products.
We first sought to summarise all available evidence in relation to vitamin D and risk of oesophageal cancer. No consistent associations were observed between vitamin D exposures and occurrence of oesophageal lesions: based on published literature, we found that better vitamin D status was associated with increased risk of oesophageal cancer. In contrast, no association was observed between dietary vitamin D intake and risk of cancer overall. However, discordant results were observed for two oesophageal cancer subtypes: a non-significantly decreased risk for squamous cell carcinoma were observed, and a non-significantly increased risk for adenocarcinoma; but a decreased risk of adenocarcinoma with higher UVB exposure was reported.
We used UK Biobank, a large cohort study of 500,000 participants to investigate the relationship between vitamin D and upper gastrointestinal cancer risk. Unfortunately, vitamin D concentration in the blood was not available for these participants. Because sunshine-induced vitamin D synthesis in skin is the key source of vitamin D for most humans, we used ambient UVB radiation at the place of residence as a marker of vitamin D status. We found a strong inverse association between annual ambient UVB and odds of developing oesophageal or gastric cancer: after adjustment for important confounders risk of these cancers was 36% reduced among those in the highest tertile of annual UVB, when compared to those with the lowest. The association was strengthened when restricted to oesophageal cancer (risk reduction: 40%), and oesophageal adenocarcinoma cases (risk reduction: 52%). In conclusion, ambient UVB radiation is inversely associated with the development of oesophageal and gastric cancer, even in Ireland, a high-latitude country.
Next, we have successfully assembled one of the largest cohorts of upper gastrointestinal cancer patients for investigation of the role of vitamin D in their survival. Concentration of 25-hydroxyvitamin D (25OHD, the best marker of vitamin D status) was measured. Our results suggest similar inconsistencies that have been previously found: for example, better vitamin D status was linked with survival in gastric cancer patients, but inverse relationship was observed for oesophageal adenocarcinoma. Overall, no firm conclusions could be made and even larger studies are needed.
We hypothesised that weight loss may be a key confounder in the study: vitamin D is released from the fat tissue following weight loss, and consequentially the concentration of 25OHD in the circulation increases. Because weight loss is common in upper gastrointestinal cancers, particularly in a more advanced disease, it might mean that vitamin D concentration acts as a marker of weight loss, which is in turn a marker of disease severity and prognosis. Hence, we investigated the modificatory role of weight loss in the relationship between vitamin D status and survival. While only suggestive associations were found, these taken together with a strong prior expectation due to the well-established link between weight loss and 25(OH)D, warrant further investigation and consideration when examining health outcomes associated with weight loss.
Finally, previous studies linked expression of VDR and CHD1 with survival in oesophageal cancer. We examined expression of CDH1 and VDR in tumour samples from 65 oesophageal cancer cases, and their relationship with cancer survival was explored. There was a significant positive association found when examining the relationship between CDH1 and survival: those with high expression of CDH1 were found to have a 54% reduced risk of mortality compared to those with low expression. Similarly, higher VDR expression was also found to be associated with a reduced risk of mortality and mortality reduction of 60% was found among those with high expression.
Taken together, these results suggest a potential beneficial role of vitamin D in upper gastrointestinal cancer. Further studies are needed to establish whether these associations are causal. Should beneficial effects of vitamin D be shown, there are no obstacles preventing the translation to clinical practice, since vitamin D is safe, inexpensive and readily available in the form of supplements and fortified products.