Vitamin D and cancer – update

Much scientific and public health interest focuses on the potential for vitamin D to reduce risk of cancer and mortality from cancer (see typical media coverage weighing up the evidence). A number of new reports shed light on the potential for vitamin D to reduce risk of specific cancers and evaluate the trade off of risks and benefits.
Colon cancer
Perhaps the strongest evidence relates to colon cancer. Substantial evidence supports a link between vitamin D and reduced incidence of colon cancer – the third most common cancer among both men and women in the United States.  Studies show that people with higher circulating vitamin D levels can have as little as half the risk of developing colon cancer as those with lower vitamin D levels (International Agency for Research on Cancer 2008). This and other possible benefits were reviewed systematically by the International Agency for Research on Cancer (IARC) (International Agency for Research on Cancer 2008), and led to the recommendation that better understanding of possible adverse health effects of population supplementation, and the possible variation in benefits depending on the baseline serum 25-hydroxyvitamin D level, are necessary before recommending routine vitamin D supplementation for cancer prevention.
New evidence fills some of this research gap. In a follow-up of the National Health and Nutrition Examination Study III, Freedman and colleagues (Freedman, Looker et al. 2010) report no overall association of blood vitamin D levels and cancer mortality during 18 years. In this study, with only 884 total cancer deaths, the overall evidence did not support protection against death from cancer. However 28.5% of the deaths were due to lung cancer and the time course for vitamin D levels to protect against this disease may not have fallen in the 18-year interval. Colon cancer, the cancer site with the strongest evidence for a protective effect of vitamin D, did show a suggested inverse relation with higher baseline vitamin D levels having lower risk of colon cancer mortality. In a more detailed analysis of the colon cancer deaths in this cohort, Fiscella and colleagues (Fiscella, Winters et al. 2010) report that excess colon cancer deaths among African Americans followed national trends. Importantly in addition to race, not having health insurance, also predicted colon cancer mortality. Low blood vitamin D levels predicted mortality from colon cancer and accounted for some, but not all, the excess risk among African Americans. 
Non-Hodgkin Lymphoma
A large study combined data from 10 cohorts to relate vitamin D blood levels and risk of developing Non-Hodgkin Lymphoma (Purdue, Freedman et al. 2010). With 1353 new cases of lymphoma this study was well suited to evaluate the overall effect and also to look at the association in different age groups and subtypes of lymphoma. There was no clear trend for vitamin D levels and risk of lymphoma overall, or in men or women when they were examined separately. This large study rules out any important protective effect of vitamin D and lymphoma risk.
Breast cancer
Epidemiologic evidence on dietary intake and also studies of blood vitamin D levels and risk of disease are inconclusive (World Cancer Research Fund 2007). Only two studies have evaluated blood levels of vitamin D at diagnosis and survival after breast cancer. The first, published last year included 512 cases of breast cancer followed for an average of 11.6 years (Goodwin, Ennis et al. 2009). 116 women developed distant recurrence and 106 died during follow-up. This study showed an increase in risk of distant recurrence and death among those with low vitamin D levels.  New data from the WHEL study of over 3,000 women with breast cancer identified 518 women with new breast cancer events during an average of 7.3 years of follow-up (Jacobs, Thomson et al. 2010). In this substantially larger study, there was no evidence for a trend in risk with level of vitamin D overall, or when pre and postmenopausal women were evaluated separately. Despite these two studies the overall level of evidence remains inconclusive with limited events to inform these analyses.
Risks and benefits
The broader evaluation of risk and benefit of vitamin D supplementation have been summarized by Bischoff-Ferrari and colleagues (Bischoff-Ferrari, Shao et al., 2010). They draw on data from 12 randomized controlled trials of vitamin D supplementation and risk of fractures which show conclusive evidence of a dose response relation between higher-does (and higher achieved blood levels of vitamin D) and significantly reduced falls and fractures. They also consider cardiovascular disease and colon cancer risk as well as possible adverse effects on serum calcium. This analysis suggests that optimal health benefits are achieved with blood vitamin D levels of 75 to 110 nmol/l., which are achieved with oral doses of 1,800 to 4,000 IU of vitamin D per day. Current intakes in adults are insufficient to bring individuals up to the protective levels of vitamin D. Further work is needed to understand how optimal blood levels can be achieved in the majority of the US population.

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