The Physicians’ Health Study (PHS) II, the only clinical trial testing a daily multivitamin, recently reported a significant 8% reduction in the primary endpoint of total cancer. We conducted expanded post hoc analyses to test the effects of a common multivitamin (daily Centrum Silver) on the risk of site-specific cancer in a randomized, double-blind, placebo-controlled trial of 14,641 U.S. male physicians initially aged ≥50 years, including 1,312 with cancer at randomization. Treatment and follow-up occurred from 1997 to 2011. Cancer endpoints were confirmed by an Endpoints Committee of physicians blinded to randomized treatment. PHS II maintained high rates of morbidity and mortality follow-up. Computing hazard ratios (HRs) and 95% confidence intervals (95% CIs), we examined the effect of a daily multivitamin on cancers grouped by anatomic site (defined by ICD9 codes) and by previously unreported cancer sites. During a median follow-up of 11.2 years among men with mean age of 64.3 y at baseline, men taking a daily multivitamin had consistent, non-significant reductions in cancers of the digestive organs and peritoneum (HR, 0.82; 95% CI, 0.67-1.00; P=.05) and respiratory and intrathoracic organs (HR, 0.81; 95% CI, 0.60-1.09; P=.17) (Table). Men with a history of cancer had a significant reduction in genitourinary cancers (HR, 0.56; 95% CI, 0.35-0.89; P=.01). For individual cancer sites, there were strong but nonsignificant reductions in brain, colon, esophageal, gallbladder, kidney, liver, myeloid myeloma, small intestine, stomach, and thyroid cancer, and nonsignificant increases in connective tissue, multiple myeloma, other lymphoid, and rectum cancer. These expanded trial data in middle-aged and older men indicate that daily multivitamin use may benefit digestive and respiratory cancers, and genitourinary cancer among men with a history of cancer. These results support the need to understand the mechanisms and long-term effects of daily multivitamin use.

HRs (95% CIs) of randomized multivitamin assignment on risk of cancer by site of malignant neoplasm 
Site of malignant neoplasm (ICD9 code) Total No. of Events Overall (n=14641)* Primary Prevention (n=13329) Secondary Prevention (n=1312) 
Lip, oral cavity, and pharynx (140-149) 50 1.27 (0.72-2.21) 1.23 (0.69-2.19) 1.96 (0.18-21.7) 
Digestive organs and peritoneum (150-159) 389 0.82 (0.67-1.00) 0.85 (0.68-1.05) 0.64 (0.36-1.11) 
Respiratory and intrathoracic organs (160-165) 176 0.81 (0.60-1.09) 0.86 (0.63-1.18) 0.48 (0.20-1.19) 
Bone, connective tissue, skin, and breast (170-175) 250 1.21 (0.94-1.55) 1.18 (0.91-1.53) 0.99 (0.53-1.83) 
Genitourinary organs (179-189) 1522 0.96 (0.87-1.06) 0.98 (0.89-1.09) 0.56 (0.35-0.89) 
Other and unspecified sites (190-199) 113 0.79 (0.55-1.15) 0.78 (0.52-1.16) 0.82 (0.31-2.23) 
Lymphatic and hematopoietic tissue (200-208) 291 0.98 (0.78-1.23) 0.94 (0.74-1.19) 1.67 (0.73-3.83) 
HRs (95% CIs) of randomized multivitamin assignment on risk of cancer by site of malignant neoplasm 
Site of malignant neoplasm (ICD9 code) Total No. of Events Overall (n=14641)* Primary Prevention (n=13329) Secondary Prevention (n=1312) 
Lip, oral cavity, and pharynx (140-149) 50 1.27 (0.72-2.21) 1.23 (0.69-2.19) 1.96 (0.18-21.7) 
Digestive organs and peritoneum (150-159) 389 0.82 (0.67-1.00) 0.85 (0.68-1.05) 0.64 (0.36-1.11) 
Respiratory and intrathoracic organs (160-165) 176 0.81 (0.60-1.09) 0.86 (0.63-1.18) 0.48 (0.20-1.19) 
Bone, connective tissue, skin, and breast (170-175) 250 1.21 (0.94-1.55) 1.18 (0.91-1.53) 0.99 (0.53-1.83) 
Genitourinary organs (179-189) 1522 0.96 (0.87-1.06) 0.98 (0.89-1.09) 0.56 (0.35-0.89) 
Other and unspecified sites (190-199) 113 0.79 (0.55-1.15) 0.78 (0.52-1.16) 0.82 (0.31-2.23) 
Lymphatic and hematopoietic tissue (200-208) 291 0.98 (0.78-1.23) 0.94 (0.74-1.19) 1.67 (0.73-3.83) 

* For the incidence of site-specific cancers, analyses wererestricted to men without that site-specific cancer at baseline.

Citation Format: Howard D. Sesso, William G. Christen, Vadim Bubes, JoAnn E. Manson, Robert J. Glynn, Julie E. Buring, J. Michael Gaziano. Multivitamins and cancer in the Physicians’ Health Study II: Expanded analyses and insights. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3245. doi:10.1158/1538-7445.AM2014-3245