Health Stream Literature Summary - Issue 58 - June 2010

Nitrate intake and the risk of thyroid cancer and thyroid disease.
Ward MH, Kilfoy BA, Weyer PJ, Anderson KE, Folsom AR and Cerhan JR. (2010) Epidemiology, 21(3); 389-395.

Thyroid cancer is the most common endocrine system malignancy and the eighth most common cancer among women. The incidence of thyroid cancer has increased substantially in the United States since 1980 for unknown reasons. Ingested nitrate inhibits the thyroid uptake of iodide and therefore potentially affects thyroid function. This study examined the relationship between nitrate intake from public water supplies and diet and the risk of incident thyroid cancer and prevalent hyperthyroidism and hypothyroidism. A questionnaire was mailed in 1986 to 98,030 randomly selected women in Iowa who were aged between 55 and 69 years. There were 41,836 women who participated in the initial survey which included questions about demographics, anthropometry, reproductive history, hormone use, family history of cancer, residence location, physical activity, smoking, alcohol consumption and medical conditions. Also included was a 126-item semi-quantitative food frequency questionnaire. A follow-up questionnaire in 1989 included information about the participants' usual source of drinking water and 36,127 women responded. Public drinking water supplies were the water source for 76% of women followed by private wells (18%) and bottled water or another source (6%). Of those women using public supplies, 85% used the supply for over 10 years and 70% used the supply for over 20 years. Women were excluded from the study if at baseline they reported cancer or if they did not respond to or died before the 1989 survey. Women were excluded if they used their public or private well supply for 10 years or less, if they lived in communities that were served by multiple water sources or communities for which no nitrate measurement data were available.

The drinking water analysis cohort included 21,977 women, 73% who used a public water supply, 25% who used a private well and 2% who used bottled water or another source. For the dietary nitrate analyses, an additional 1326 women were excluded due to missing or presumed erroneous data. Nitrate levels in Iowa public water supplies were available from historical monitoring data but no nitrate measurement data were available for women using private wells. Women who were well-water users were compared with women using public supplies with the lowest quartile of nitrate to determine the association of private well use with thyroid cancer and conditions. The cohort was traced annually for cancer incidence by linking personal identifiers to the State Health Registry of Iowa's cancer database.

During the 19 years of follow-up, 45 cases of thyroid cancer were diagnosed. The median time from enrolment to diagnosis was 9.3 years. In the cohort 3151 women reported ever having hypothyroidism and 1009 reported ever having hyperthyroidism. There was little evidence for an association of thyroid cancer incidence with use of a private well as a drinking water source. However, for public water supplies, increased mean nitrate concentration was associated with increasing risk of thyroid cancer (P for trend = 0.02). Compared with women in the lowest quartile, risk was elevated 2.2-fold (95% CI = 0.83-5.76) for the highest quartile. Risk was found to increase 2.6-fold (1.09-6.19) for the highest versus lowest category of years of use of a public water supply with nitrate levels greater than 5 mg/L (P for trend = 0.04). Increasing intake of nitrate from dietary sources was also found to be associated with increasing risk of thyroid cancer. The relative risk was 2.9 (1.00-8.11) for those in the highest versus the lowest quartile of dietary nitrate (P for trend = 0.046). No association was found between the prevalence of hypothyroidism and hyperthyroidism with either the mean nitrate concentration in public water suppliers or increasing years of nitrate levels greater than 5 mg/L. The use of private wells was not associated with risk of either condition. Increasing intake of nitrate from dietary sources was associated with increased prevalence of hypothyroidism (P for trend = 0.001). When those with the lowest intake were compared with those with the highest intake quartile, there was a 24% higher prevalence of hypothyroidism (95% CI = 1.10-1.40). There was no association found with hyperthyroidism.

In this study nitrate ingestion from dietary and drinking water sources was associated with an increased risk of thyroid cancer which has not been seen in previous studies, and higher intake of dietary nitrate was associated with hypothyroidism. The findings for thyroid cancer were based on small numbers and larger studies are required to clarify the study findings and to evaluate the potential interaction between nitrate ingestion and factors that affect rates of endogenous nitrosation. The study results are biologically plausible and are consistent with animal data. As the incidence of thyroid cancer has increased during the past decades, with no identifiable cause, the possible role of nitrate needs to be considered in future epidemiological studies of thyroid cancer and thyroid conditions.

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