TOPLINE

A large population-based study found that higher dietary nitrite intake over 20 years was associated with an increased risk for colorectal cancer in men but not in women. The link was strongest for distal colon cancer, where men with the highest nitrite consumption had a 50% higher risk.

METHODOLOGY

• Nitrate and nitrite are ions that naturally occur in water, soil, and plants and are commonly used as food additives, particularly cured meats. In the body, nitrite can generate N-nitroso compounds, some of which are animal carcinogens. Observational studies have tied higher nitrite intake to increased risk for gastric and esophageal cancers. 
• To study the relationship between long-term nitrate and nitrite intake and colorectal cancer, researchers analyzed data from 82,009 middle-aged and older Swedish adults in two population-based cohorts (Swedish Mammography Cohort and Cohort of Swedish Men). 
• Participants completed food frequency questionnaires (FFQs) in 1997, 2009, and 2019. Nitrate and nitrite intake was estimated by linking the FFQ data to a food and drinking water database. 
• Incident colorectal cancer cases were ascertained through the Swedish Cancer Registry from 1998 to 2022. Exposure-outcome associations were adjusted for family history of colorectal cancer, education, BMI, smoking, physical activity, alcohol consumption, and fiber intake. 

TAKEAWAY

• Over 1,600,476 person-years of follow-up, there were 3170 incident colorectal cancer cases. Among men, meat accounted for roughly half of nitrite intake at baseline, with processed meats contributing 26%; vegetables were the other main source. Among women, vegetables accounted for 68% of nitrite intake, and processed meats for 24%.
• No associations were observed between dietary nitrate intake and the risk for colorectal cancer. But higher nitrite intake was associated with an increased risk among men only (highest vs lowest quintiles, hazard ratio [HR], 1.23; P for trend < .05). 
• In a subsite analysis, nitrite intake was most strongly associated with the risk for distal colon cancer in men (HR, 1.50; P for trend = .024), with nonsignificant elevated risks for proximal colon cancer (HR, 1.18; 95% CI, 0.90-1.56) and rectal cancer (HR, 1.15; 95% CI, 0.90-1.47). 
• There was no evidence for effect modification by vitamin C or heme iron on the association between nitrite intake and colorectal risk in either sex (P for interaction > .05 for all comparisons) — despite previous evidence suggesting that antioxidants mitigate and heme iron enhances the formation of N-nitroso compounds. 

IN PRACTICE

“In this population-based prospective cohort study with time-varying exposures, we observed that a higher nitrite intake was associated with higher risk of colorectal cancer in men, but not in women,” the study authors wrote. They noted that men generally had higher nitrite intake over time than women did, but further research is needed to understand the sex-based differences observed.

SOURCE

The study, led by Ana Rodrigues, MMedSc, of the Karolinska Institute in Stockholm, Sweden, was published online in the Journal of the National Cancer Institute.

LIMITATIONS

Although validity and reproducibility of the FFQs were acceptable, diet data were self-reported, and weaker correlations with some major dietary contributors to nitrate and nitrite likely contributed to exposure misclassification. The possibility of unmeasured confounding cannot be ruled out, by factors such as the gut microbiome and underlying gastrointestinal conditions that could affect dietary habits.

DISCLOSURES

The Swedish Research Council funded the work. Two authors disclosed being co-inventors of patents related to medical uses of inorganic nitrate and nitrite.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.