Contents - IARC

Vitamin D and Cancer
These compounds were initially shown to modulate differentiation in many experimental systems (IARC, 1998b, 1999). No
significant effects on mortality rates were observed for supplementation with a combination of retinol and zinc (Blot et
al.,1993), or beta-carotene and vitamin A (Omenn et al.,1996). One large randomised trial of a vitamin A analogue, feretinide
showed no impact on the occurrence of secondary breast cancer in breast cancer survivors (Veronesi et al.,1999). In 1998,
systematic reviews by IARC Expert Groups concluded that there was evidence suggesting a lack of anti-cancer activity of
preformed vitamin A compounds, and thus also of vitamin A (Table 1) (IARC, 1998b). Similar conclusions were reached with
retinoids, a class of compounds structurally related to vitamin A (IARC 1999). Also, some of these retinoid compounds are
teratogenic in humans or in animals (Table 1) (IARC, 1999).
Vitamin C
Vitamin C is deemed to be a free-radical scavenger, and high intakes of foodstuffs rich in vitamin C (e.g., citrus fruits) could
play a role in decreasing gastric cancer incidence. Double-blind randomised trials of supplementation with ascorbic acid (1g
twice per day) combined with other anti-oxidants (usually vitamin E, selenium, beta-carotene) in populations at high risk for
gastric cancer in China and Venezuela did not result in higher rates of regression of dysplastic lesions in the stomach (You et
al.,2006; Plummer et al.,2007).
Vitamin E
Vitamin E has anti-oxidant properties that were deemed to play a role in controlling cellular oxidative damage. In the ATBC
study (ATBC, 1994) the group receiving a vitamin E supplement (50 IU per day) had no reduction in lung cancer incidence
but a 34% reduction in prostate cancer incidence. However deaths from cerebrovascular accidents doubled. A randomised
placebo-controlled trial within the Women’s Health Initiative Study found no effect of 600 IU per day of vitamin E on cancer risk
(Lee et al.,2005). A meta-analysis of vitamin E supplementation including 16 randomised trials suggests that high doses of
vitamin E supplementation above 200 IU per day may increase all-cause mortality (Miller et al.,2005).
Selenium
Selenium is involved in defence mechanisms against oxidative stress through selenoproteins. Selenium at high doses is
known to be toxic. Selenium supplementation with doses around 200µg per day was thought to prevent non-melanoma skin
cancer, and colorectal and prostate cancer. Selenium has been part of several trials, but it was often mixed with vitamins and
it is thus difficult to isolate an effect specific to this compound.
The Nutritional Prevention of Cancer (NPC) Trial (Clark et al.,1996) was a placebo-controlled randomised trial to test whether
selenium supplements could reduce the incidence of non-melanoma skin cancer. The incidence of non-melanoma skin
cancer remained the same in the intervention and in the placebo groups. However the group that received the supplement
had statistically significant reductions of approximately 40% and 50% in overall cancer incidence and cancer mortality,
respectively. Main reductions in incidence were observed for prostate, colorectal and lung cancer. Separate follow-up of lung
cancer and prostate cancer showed a reduction of the incidence of these two cancers in subjects who had low serum
selenium levels at baseline, and not in subjects with higher levels at baseline (Reid et al.,2002; Duffied-Lillico et al.,2002). A reanalysis
of the trial data showed that all the protective effect was confined to males, and that selenium supplements
decreased cancer risk in subjects with low serum selenium levels at baseline, whereas these supplements seemed to
increase cancer risk in subjects with high selenium levels at baseline (Duffield-Lillico et al.,2002).
A randomised trial organised within the NPC Trial failed to show reduction of colonic polyps with selenium supplementation
(Reid et al.,2006), but again, a significant decrease was noticeable among subjects with low serum selenium levels at
baseline while in subjects with high serum selenium level at baseline, the frequency of polyps was greater, although
statistically not significant.
Recent results of the Third National Health and Nutrition Examination Survey (NHANES III) cohort study in the USA calls for
caution with use of this compound, as the study suggests a U shaped curve in associated risk with serum selenium levels and
all-cause and cancer mortality. Higher mortality was observed in subjects with low or with high serum levels of selenium, and
lower mortality around some optimal serum levels (Bleys et al.,2008).
Therefore, supplementation with selenium has little influence on cancer risk, and instead can be detrimental for subjects who
have high levels of serum selenium.
Folic acid
Folic acid plays an important role in DNA repair, synthesis and methylation reactions. Two randomised placebo-controlled
trials indicate that folic acid supplements may in reality increase the risk of colorectal and prostate cancer, and of
adenomatous polyps (Lonn et al.,2006; Cole et al.,2007).
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