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Vitamin D and cancer survival

Scientists are saying that although sunbathing is known to cause skin cancer, it may also help people survive when they get it, The Independent reported.

The newspaper said that two studies have found that vitamin D, “may help improve survival for patients with skin and bowel cancer”. Professor Newton Bishop, lead author of the skin cancer study, is reported as suggesting that melanoma patients could get vitamin D from fatty fish or by taking supplements, but also warning: “There is some evidence from other studies that high levels of vitamin D are also harmful. So we should aim for a normal level rather than a very high one.”

These two studies assessed vitamin D levels in patients with colorectal cancer or melanoma. The colorectal cancer study found a link between higher vitamin D levels and increased survival, while the skin cancer study found a link between higher vitamin D levels and a reduced risk of relapse.

However, despite their findings, it is possible that vitamin D itself did not cause these improvements, and that some other factor is responsible. Further research is needed to study this link, and until then, the best advice is to maintain normal vitamin D levels through a healthy diet that includes food that contains vitamin D, and through normal daylight exposure. The risks of excessive sun exposure are well established and sunbathing and sunbeds cannot be recommended.

Where did the story come from?

These news reports are based on two separate studies published in peer-reviewed journals.

The colorectal cancer study was carried out by Professor Kimmie Ng and colleagues from the Dana-Farber Cancer Institute as well as other research centres in the US. It was published in the British Journal of Cancer. No sources of funding were reported.

The skin cancer study was carried out by Professor Julia A Newton-Bishop and colleagues from the Leeds Institute of Molecular Medicine and other research centres in the US and the UK. It was published in the Journal of Clinical Oncology. The study was funded by Cancer Research UK, the Skin Cancer Research fund and the National Institutes of Health in the US.

What kind of scientific study was this?

Both studies investigated whether vitamin D levels are related to outcome in people who have cancer.

Colorectal cancer study

This prospective cohort study investigated if levels of vitamin D in the blood were related to survival in people with colorectal cancer. The participants were acquired from two other cohort studies, the Nurses’ Health Study and Health Professionals Follow-Up Study. These participants had been mailed questionnaires about their health and risk factors every two years. The researchers used their responses to identify anyone diagnosed with colorectal cancer between 1986 and 2004.

This resulted in 1,017 patients with colorectal cancer, the diagnosis of which was confirmed by checking medical records. Patients were followed up until they died, or until 2006. Deaths were reported by family members or the postal authorities, and people who did not respond to the questionnaires were searched for in the National Death Index.

Vitamin D levels were estimated using the patients’ race and geographic region, dietary vitamin D intake, body mass index (BMI), and physical activity reported either just before diagnosis (to estimate pre-diagnosis levels) or one to four years after diagnosis (to estimate post-diagnosis levels). This was done using a mathematical model that had been developed and validated in men taking part in one of the original cohort studies.

The researchers then looked at the relationship between vitamin D levels and length of time an individual survived after a diagnosis of colorectal cancer. They took into account factors that could affect survival, such as age, tumour characteristics, year of diagnosis, BMI, physical activity, total energy-adjusted calcium intake, and which cohort the participant came from.

Skin cancer study

This study used both retrospective and prospective methods to look at the relationship between vitamin D levels and risk of relapse from melanoma (the most serious form of skin cancer).

The retrospective part of the study used a case–control design. It compared 131 people with melanoma that had relapsed (cases) with 169 patients with melanoma that had not relapsed (controls). Cases and controls were matched for age, gender, and thickness of their tumour (called Breslow thickness). Participants had all had been diagnosed at least three years earlier without previous relapse; all tumours were thicker than 0.75mm.

The participants filled out questionnaires about their use of supplements in the year before the interview, and gave a blood sample for vitamin D measurement and DNA analysis. People taking multivitamins or fish oils were both classed as having taken vitamin D supplements. Analyses looked at the effect of vitamin D supplementation and genetic make-up (vitamin D receptor) on relapse.

The prospective study recruited a cohort of 872 people with a recent diagnosis of melanoma (stages I to IIIA; all tumours over 0.75mm thickness) and followed them up for an average (median) of 4.7 years. The participants filled out a questionnaire about their supplement use, drug intake, height and weight, and provided a blood sample. Relapse and survival were assessed using annual questionnaires, cancer registry data, and the participants’ clinical notes.

Vitamin D2 and D3 levels were measured, but vitamin D2 was undetectable in the samples. Average vitamin D levels were adjusted to take into account gender, age, BMI, and month in which the sample was taken. Analyses looked at the effect of vitamin D supplementation, and levels of vitamin D in the blood on relapse and survival.

What were the results of the study?

Colorectal cancer study

Of the 1,017 participants, 119 people died from colorectal cancer, and 164 people died from other causes (283 deaths in total). Average (median) estimated levels of vitamin D in the blood were 27.17 nanograms per millilitre for female participants, and 29.18 nanograms per millilitre for male participants.

People with higher estimated levels of vitamin D post-diagnosis had lower death rates from colorectal cancer and from any cause. People estimated as being in the highest 20% were half as likely to die over the follow-up period as those in the lowest 20%. This association was not affected when BMI or physical activity were taken into account. Vitamin D levels estimated pre-diagnosis were also associated with lower rates of deaths from colorectal cancer and from any cause, but this association was no longer significant if other factors such as BMI and physical activity were taken into account.

Skin cancer study

In the case control study, a larger proportion of those participants that did not experience a relapse (‘non-relapsers’; ([42%] 62 of 149) reported regularly using any supplements in the previous year than those who experienced a relapse ([31%] 28 of 91), but this difference was not statistically significant. Non-relapsers had higher levels of vitamin D in their blood than relapsers (49 nanomoles per litre compared with 46 nanomoles per litre), but this difference was also not statistically significant.

In the prospective study, most of the melanoma patients’ vitamin D levels were “suboptimal” (less than 60 nanomoles per litre). Increased vitamin D levels in the blood were associated with a thinner thickness of the tumour. People with higher vitamin D levels were less likely to relapse during follow up, and this association remained significant after taking into account factors that might affect results, including age, gender, tumour site and thickness, BMI and deprivation.

Although there was an association between higher vitamin D levels and survival, this association was no longer significant once these factors were taken into account. Using vitamin D supplements did not affect relapse or survival.

What interpretations did the researchers draw from these results?

The conclusion of the colorectal cancer study was that, “higher predicted [vitamin D] levels after a diagnosis of colorectal cancer may be associated with improved survival” and that further research into this link is warranted.

The researchers in the skin cancer study conclude that it suggests a role for vitamin D in melanoma outcome and the prospective study is evidence that vitamin D levels at diagnosis are linked to thinner tumours and better survival. They suggest, “patients with melanoma, and those at high risk of melanoma, should seek to ensure vitamin D sufficiency”, and say this could be achieved with vitamin D supplements.

What does the NHS Knowledge Service make of this study?

Colorectal cancer study

There are a number of considerations to take into account when interpreting these findings:

  • As with all studies of this type, an association between two factors does not necessarily mean that one causes the other. Although the researchers did take a number of factors into account in their analyses, there may be other unknown or unmeasured factors having an effect.
  • Although lower vitamin D levels were associated with poorer outcomes in this study, this does not necessarily mean that increasing vitamin D intake would reduce risk of death from colorectal cancer. Randomised controlled trials would be needed to test this possibility.
  • This study did not measure vitamin D levels in the participants but estimated them based on a mathematical model developed and tested in men who did not have cancer. The fact that the model was tested is an advantage, but it is possible that the model may not work as well in women or in people with cancer.

The researchers did not have information on the treatments received by patients. They attempted to take this into account by considering the year that cancer was diagnosed (as treatments have changed over time), and say that large differences in treatment were unlikely as participants were all similar in terms of socioeconomic status and education (all participants were health professionals). However, differences in treatment could still be having an effect.

Skin cancer study

As an observational study it shares some of the limitations of the colorectal cancer study, including the inability to determine if vitamin D itself is causing the differences seen in relapse or whether this is due to other confounding factors. This study found that the effect on survival across seasons was not significant after taking into account other factors.

These findings are likely to lead to further research investigating the identified links. Until the reasons for these associations become apparent, most people can achieve normal levels of vitamin D through a healthy diet including foods containing vitamin D, and through normal daylight exposure.

Advice about sensible sun exposure should be followed. The risks of excessive exposure are well established and should be avoided wherever possible, including avoiding sunbeds and getting sunburnt.

Links to the headlines

Exposure to sun ‘may help people with cancer survive’. The Independent, September 22 2009

Links to the science

Ng K, Wolpin BM, Meyerhardt JA, et al. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. British Journal of Cancer (2009) 101, 916–923

Newton-Bishop JA, Beswick S, Randerson-Moor J,  et al. Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma. JCO Early Release, published online ahead of print Sep 21 2009

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