Interaction of Nitrate and Folate on the Risk of Breast Cancer Among Postmenopausal Women

Inoue-Choi, Maki; Ward, Mary H.; Cerhan, James R.; Weyer, Peter J.; Anderson, Kristin E.; Robien, Kim

doi:10.1080/01635581.2012.687427

Cited by 28 publications

(29 citation statements)

References 43 publications

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“…Inoue-Choi et al [17] also confirmed the relationship between a dose of these compounds and their action. They demonstrated a significantly increased risk of breast cancer among women taking 400 μg of folate per day in the form of dietary supplements, but they were also additionally exposed to a high nitrate supply contained in the drinking water, which provided carcinogenic nitroso compounds.…”

Section: Vitamin Chemoprevention?supporting

confidence: 58%

B-Group Vitamins: Chemoprevention?

Gruber¹

2016

Adv Clin Exp Med

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The importance of vitamins in the prevention of cancer has attracted the attention of consumers, nutritionists and scientists for decades. The mechanisms of carcinogenesis, extended in the context of the function of vitamins, i.e. regulation of and participation in metabolic processes in the cell, suggest a substantial impact of these compounds on the initial stages of carcinogenesis. One-carbon metabolism involving folic acid, vitamins B2, B6 and B12, and folate metabolism doesn't only generate methyl groups, thus determining epigenetic processes, modifications of the genome and carcinogenesis. It also provides the compounds involved in the DNA synthesis and repair processes, especially the synthesis of purines and pyrimidines and the conversion of dUMP (2-deoxyuridine monophosphate) to dTMP (2-deoxythymidine monophosphate). In light of these pathways, folate, together with vitamins B2, B6 and B12, became a subject of interest as compounds whose deficit or surplus can potentially have an impact on the processes of carcinogenesis. Literature reports, however, do not fully confirm that the influence on the synthesis of nucleotides is connected with the inhibition of carcinogenesis. The impact of individual vitamins involved in one-carbon metabolism on carcinogenesis and their role in the prevention of these conditions depend on the type of cancer and the dose administered. Nevertheless, the research conducted makes it possible to conclude a considerable and probably long-underestimated role of these compounds in the prevention of serious, difficult to treat or incurable diseases (Adv Clin Exp Med 2016, 25, 3, 561-568).

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Section: Vitamin Chemoprevention?supporting

confidence: 58%

B-Group Vitamins: Chemoprevention?

Gruber¹

2016

Adv Clin Exp Med

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“…Higher dietary nitrate intake was observed among IWHS participants reporting higher age, BMI, education level, alcohol intake, physical activity level and estrogen use. 25 Women reporting higher dietary nitrate intake also reported higher intake of total calories, cruciferous vegetables, red meats and vitamins C and E. Higher dietary nitrate intake was associated with lower ovarian cancer risk (HR Q5 vs.Q1 5 0.61, CI 5 0.40-0.95; p trend 5 0.02, Table 4). Dietary nitrite intake was not associated with ovarian cancer risk.…”

Section: Resultsmentioning

confidence: 91%

Nitrate and nitrite ingestion and risk of ovarian cancer among postmenopausal women in Iowa

Inoue-Choi

Jones

Anderson

et al. 2014

Intl Journal of Cancer

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Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women’s Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO3-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each woman’s duration at the residence. We computed multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CI=1.22–3.38, ptrend=0.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3-N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HR=1.53, CI=0.93–2.54) compared with the same reference group. Associations were stronger when vitamin C intake was

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“…Overall, the Panel considered that, for lung cancer, information is still too sparse to draw meaningful conclusions, although there was no evidence that nitrate intake is associated with increased risk of lung cancer. -Choi et al (2012) evaluated in a prospective cohort study (22 years) the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women's Health Study. A self-administered FFQ (127 items) and a health and lifestyle questionnaire were completed by 34,388 post-menopausal women (mean age 61.6 years, SD 4.2 years).…”

Section: Discussionmentioning

confidence: 99%

Re‐evaluation of sodium nitrate (E 251) and potassium nitrate (E 252) as food additives

Mortensen¹,

Aguilar²,

Crebelli³

et al. 2017

EFS2

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The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re‐evaluating the safety of sodium nitrate (E 251) and potassium nitrate (E 252) when used as food additives. The current acceptable daily intakes (ADIs) for nitrate of 3.7 mg/kg body weight (bw) per day were established by the SCF (1997) and JECFA (2002). The available data did not indicate genotoxic potential for sodium and potassium nitrate. The carcinogenicity studies in mice and rats were negative. The Panel considered the derivation of an ADI for nitrate based on the formation of methaemoglobin, following the conversion of nitrate, excreted in the saliva, to nitrite. However, there were large variations in the data on the nitrate‐to‐nitrite conversion in the saliva in humans. Therefore, the Panel considered that it was not possible to derive a single value of the ADI from the available data. The Panel noticed that even using the highest nitrate‐to‐nitrite conversion factor the methaemoglobin levels produced due to nitrite obtained from this conversion would not be clinically significant and would result to a theoretically estimated endogenous N‐nitroso compounds (ENOC) production at levels which would be of low concern. Hence, and despite the uncertainty associated with the ADI established by the SCF, the Panel concluded that currently there was insufficient evidence to withdraw this ADI. The exposure to nitrate solely from its use as a food additive was estimated to be less than 5% of the overall exposure to nitrate in food based on a refined estimated exposure scenario. This exposure did not exceed the current ADI (SCF, 1997). However, if all sources of exposure to dietary nitrate are considered (food additive, natural presence and contamination), the ADI would be exceeded for all age groups at the mean and the highest exposure.

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Interaction of Nitrate and Folate on the Risk of Breast Cancer Among Postmenopausal Women

Cited by 28 publications

References 43 publications

B-Group Vitamins: Chemoprevention?

B-Group Vitamins: Chemoprevention?

Nitrate and nitrite ingestion and risk of ovarian cancer among postmenopausal women in Iowa

Re‐evaluation of sodium nitrate (E 251) and potassium nitrate (E 252) as food additives

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