Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study.
Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
Curt T
CT
Dellavalle
Qian
Q
Xiao
Gong
G
Yang
Xiao-Ou
XO
Shu
Briseis
B
Aschebrook-Kilfoy
Wei
W
Zheng
Hong
H
Lan Li
Bu-Tian
BT
Ji
Nathaniel
N
Rothman
Wong-Ho
WH
Chow
Yu-Tang
YT
Gao
Mary H
MH
Ward
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000009:adverse effects; D002471:Cell Transformation, Neoplastic; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D004032:Diet / Q000009:adverse effects*; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D008460:Meat; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects*; D009573:Nitrites / Q000008:administration & dosage / Q000009:adverse effects*; D009603:Nitroso Compounds / Q000009:adverse effects; D011446:Prospective Studies; D012306:Risk; D011795:Surveys and Questionnaires; D016387:Women's Health
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D001205:Ascorbic Acid
N-nitroso compounds; colon cancer; diet; nitrate; nitrite; rectum cancer; vitamin C