Background Whether vitamin D supplementation reduces cancer or cardiovascular disease remains unclear, and randomized trial evidence is limited. Methods The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2X2 factorial trial of vitamin D3 (cholecalciferol, 2000 IU/day) and marine omega-3 fatty acids (1 g/day) for the prevention of cancer and cardiovascular disease. There were 25,871 U.S. men aged ≥50 and women aged ≥55, including 5,106 African Americans, who participated. Primary endpoints were total invasive cancer and major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular mortality). Secondary endpoints included site-specific cancers, cancer mortality, and additional cardiovascular events. Results Vitamin D supplementation did not reduce either of the primary endpoints. During a median 5.3 year intervention, 1,617 participants were diagnosed with cancer (793 assigned to vitamin D and 824 assigned placebo; hazard ratio [HR]=0.96; 95% confidence interval, 0.88–1.06; p-value=0.47); and 805 experienced a major cardiovascular event (396 assigned to vitamin D and 409 assigned to placebo; HR=0.97 [0.85–1.12]; p-value=0.69). For secondary endpoints, the hazard ratios and 95% confidence intervals comparing Vitamin D to placebo were: cancer deaths (n=341, HR 0.83 (0.67–1.02); breast cancer (1.02; 0.79–1.31); prostate cancer 0.88 (0.72–1.07); colorectal cancer 1.09 (0.73–1.62); expanded cardiovascular disease events 0.96 (0.86–1.08); myocardial infarction 0.96 (0.78–1.19); stroke 0.95 (0.76–1.20); and cardiovascular mortality 1.11 (0.88–1.40). The HR for all-cause deaths (n=978) was 0.99 (0.87–1.12). No excess risks of hypercalcemia or other adverse events were identified. Conclusion Vitamin D supplementation did not reduce invasive cancer incidence or cardiovascular events.

Background Whether omega-3 fatty acid supplementation reduces risk of cardiovascular disease or cancer remains unclear. Methods The VITamin D and OmegA-3Trial (VITAL) was a randomized, placebo-controlled, 2X2 factorial trial of vitamin D3 (2000IU/day) and marine omega-3 fatty acids (1 g/day) in the primary prevention of cardiovascular disease and cancer among 25,871 U.S. men aged ≥50 and women aged >55, including 5,106 African Americans. Primary endpoints were major cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality) and total invasive cancer. Secondary outcomes included individual components of the cardiovascular composite, the composite plus coronary revascularization, site-specific cancers, and cancer mortality. This paper reports the results of omega-3 and placebo. Results During a median 5.3 years, rates of the primary outcomes did not differ between the omega-3 and placebo groups -- 805 participants had a major cardiovascular event, hazard ratio [HR]= 0.92; 95% confidence interval [CI], 0.80–1.06, p= 0.24. Invasive cancer was diagnosed in 1,617 participants, HR 1.03 (0.93-1.13, p=0.56). In the analysis of key secondary endpoints, hazard ratios and 95% CIs comparing omega-3 to placebo were: expanded cardiovascular events, HR 0.93 (0.82-1.04); total myocardial infarction HR 0.72 (0.59-0.90); total stroke, HR 1.04 (0.83-1.31); cardiovascular mortality HR 0.96 (0.76-1.21); and cancer deaths (n=341, HR 0.97 (0.79-1.20). For all-cause mortality (n=978), the HR was 1.02 (0.90-1.15). No excess risks of bleeding or other serious adverse events were observed. Conclusions Omega-3 fatty acid supplementation did not reduce major cardiovascular events or cancer incidence.

The Women's Health Study trial previously reported no overall effect of low-dose aspirin (100 mg every other day) on invasive breast cancer over an average of 10 years of treatment. The present subgroup analyses further show no effects by tumour characteristics at diagnosis, suggesting that low-dose aspirin has no preventive effect on breast cancer. Aspirin inhibits cyclooxygenase enzymes (COX-1 and -2) (DuBois, 2004). Cyclooxygenase 2 (COX-2) overexpression induces the occurrence of mammary tumours in transgenic mice (Liu et al, 2001). Prostaglandin E2 that is generated from COX-2 overexpression stimulates the expression of cytochrome P450 aromatase, a key enzyme in local oestrogen production, and induces angiogenesis (DuBois, 2004). Cyclooxygenase 2 overexpression occurs in approximately 40% of invasive breast cancer, and is more common in tumours with large size, lymph node metastasis, a ductal type of histology, high histological grade, or negative hormone receptor status (Ristimaki et al, 2002). Thus, the effect of aspirin may be stronger in these subtypes of tumours.In July 2005, the Women's Health Study (WHS) reported overall results from the only randomised trial of aspirin and cancer risk in women (Cook et al, 2005). After an average of 10 years of treatment and follow-up, low-dose aspirin (100 mg every other day) had no effect on risk of invasive breast cancer overall or by combined hormone receptor status in 39 876 women aged X45 years. In a subgroup analysis, we evaluate whether low-dose aspirin might reduce risk according to tumour characteristics at diagnosis. MATERIALS AND METHODS Study designDuring 1992 -1996, a total of 39 876 women with no history of cancer or cardiovascular disease were enrolled and randomised into a 2 Â 2 factorial design of low-dose aspirin (100 mg every other day, provided by the Bayer HealthCare, Leverkusen, Germany) and vitamin E (600 IU every other day, provided by the Natural Source Vitamin E Association) for the primary prevention of cancer and cardiovascular disease (Clinicaltrials.gov identifier, NCT00000479). The methods of the study design have been described in detail previously (Cook et al, 2005). Written informed consent was obtained from each participant. The trial was approved by the Human Subjects Committee at the Brigham and Women's Hospital and monitored by an external Data and Safety Monitoring Board.Annually, participants were sent monthly calendar packs containing study medications, and questionnaires inquiring about potential adverse effects, adherence to pill taking, and occurrence of disease outcomes. Study medications and disease ascertainment were continued in blinded fashion through the scheduled end of the trial (31 March 2004). Deaths of participants were identified by reports from family members, postal authorities, and a search of the National Death Index. Morbidity and mortality follow-up were 97.2 and 99.4% complete, respectively (Cook et al, 2005).For reported diagnoses of breast cancer, medical records and other relevant information were so...

The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

SummaryWe conducted a case-control study of 394 women with breast cancer and 788 control women (91% response) to investigate the association of lifetime physical activity with mainly menopausal breast cancer risk. After controlling for potential confounders, the odds ratios (95% confidence intervals) for increasing quartiles of lifetime physical activity were 1.00 (referent), 0.91 (0.60-1.37), 0.91 (0.60-1.39), and 1.10 (0.73-1.67), respectively; P, trend = 0.47. We also separately examined physical activity at ages 12-18, 19-34, 35-49 and ≥50 years; no significant trends were observed in any age group. These data do not support a role of physical activity in preventing breast cancer.

In a nested case-control study of 513 women with cancer; 130 with cardiovascular disease and equal numbers of controls, we found no effect of randomised beta-carotene on risk of cancer or cardiovascular disease within any quartile of baseline plasma beta-carotene, nor was there a trend across quartiles (P for trend 0.15 and 0.62, respectively).

No abstract

No abstract