Briseis A. Kilfoy

International patterns and trends in thyroid cancer incidence, 1973–2002

During the past several decades, an increasing incidence of thyroid cancer has been reported in many parts of the world. To date, no study has compared the trends in thyroid cancer incidence across continents. We examined incidence data from cancer incidence in five continents (CI5) over the 30-year period 1973–2002 from 19 populations in the Americas, Asia, Europe, and Oceania. Thyroid cancer rates have increased from 1973–1977 to 1998–2002 for most of the populations except Sweden, in which the incidence rates decreased about 18% for both males and females. The average increase was 48.0% among males and 66.7% among females. More recently, the age-adjusted international thyroid cancer incidence rates from 1998 to 2002 varied 5-fold for males and nearly 10-fold for females by geographic region. Considerable variation in thyroid cancer incidence was present for every continent but Africa, in which the incidence rates were generally low. Our analysis of published CI5 data suggests that thyroid cancer rates increased between 1973 and 2002 in most populations worldwide, and that the increase does not appear to be restricted to a particular region of the world or by the underlying rates of thyroid cancer.

Nitrate Intake and the Risk of Thyroid Cancer and Thyroid Disease

Background: Nitrate is a contaminant of drinking water in agricultural areas and is found at high levels in some vegetables. Nitrate competes with uptake of iodide by the thyroid, thus potentially affecting thyroid function. Methods: We investigated the association of nitrate intake from public water supplies and diet with the risk of thyroid cancer and self-reported hypothyroidism and hyperthyroidism in a cohort of 21,977 older women in Iowa who were enrolled in 1986 and who had used the same water supply for >10 years. We estimated nitrate ingestion from drinking water using a public database of nitrate measurements (1955–1988). Dietary nitrate intake was estimated using a food frequency questionnaire and levels from the published literature. Cancer incidence was determined through 2004. Results: We found an increased risk of thyroid cancer with higher average nitrate levels in public water supplies and with longer consumption of water exceeding 5 mg/L nitrate-N (for ≥5 years at >5 mg/L, relative risk [RR] = 2.6 [95% confidence interval (CI) = 1.1–6.2]). We observed no association with prevalence of hypothyroidism or hyperthyroidism. Increasing intake of dietary nitrate was associated with an increased risk of thyroid cancer (highest vs. lowest quartile, RR = 2.9 [1.0–8.1]; P for trend = 0.046) and with the prevalence of hypothyroidism (odds ratio = 1.2 [95% CI = 1.1–1.4]), but not hyperthyroidism. Conclusions: Nitrate may play a role in the etiology of thyroid cancer and warrants further study.

Gender is an Age-Specific Effect Modifier for Papillary Cancers of the Thyroid Gland

Background: Thyroid cancer incidence rates have increased worldwide for decades, although more for papillary carcinomas than other types and more for females than males. There are few known thyroid cancer risk factors except female gender, and the reasons for the increasing incidence and gender differences are unknown. Methods: We used the National Cancer Institutes Surveillance, Epidemiology, and End Results 9 Registries Database for cases diagnosed during 1976-2005 to develop etiological clues regarding gender-related differences in papillary thyroid cancer incidence. Standard descriptive epidemiology was supplemented with age-period-cohort (APC) models, simultaneously adjusted for age, calendar-period and birth-cohort effects. Results: The papillary thyroid cancer incidence rate among females was 2.6 times that among males (9.2 versus 3.6 per 100,000 person-years, respectively), with a widening gender gap over time. Age-specific rates were higher among women than men across all age groups, and the female-to-male rate ratio declined quite consistently from more than five at ages 20-24 to 3.4 at ages 35-44 and approached one at ages 80+. APC models for papillary thyroid cancers confirmed statistically different age-specific effects among women and men (P < 0.001 for the null hypothesis of no difference by gender), adjusted for calendar-period and birth-cohort effects. Conclusion: Gender was an age-specific effect modifier for papillary thyroid cancer incidence. Future analytic studies attempting to identify the risk factors responsible for rising papillary thyroid cancer incidence should be designed with adequate power to assess this age-specific interaction among females and males. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1092–100)

A Birth Cohort Analysis of the Incidence of Papillary Thyroid Cancer in the United States, 1973–2004

BACKGROUND The incidence of papillary thyroid cancer has been reported to be increasing during the past three decades, with a 65-126% increase between 1975 and 2004. The reason for the increase is currently unknown. This study examined the incidence pattern of papillary thyroid cancer in the United States, and evaluated the components of birth cohort (defined based on year of birth), time period, and age as determinants of the observed time trend of the disease. METHODS Using the data from the National Cancer Institutes Surveillance, Epidemiology, and End Results program for 1973-2004, we conducted both univariate analysis and age-period-cohort modeling to evaluate birth cohort patterns and evaluate age, period, and cohort effects on incidence trends over time. RESULTS The increasing incidence showed a clear birth cohort pattern for both men and women. The results from age-period-cohort modeling showed that, while period effect appeared to have had an impact on the observed incidence trends, birth cohort effect may also explain part of the increasing trend in papillary thyroid carcinoma during the study period, especially among women. CONCLUSION While a period effect that is likely due to advancements in diagnostic techniques and increased medical detection of small thyroid nodules may explain some of the observed increase in the incidence, we speculate that birth cohort-related changes in environmental exposures (such as increased exposure to diagnostic X-rays and polybrominated diphenyl ethers) have also contributed to the observed increase in papillary thyroid cancer during the past decades.

Lymphoma survival patterns by WHO subtype in the United States, 1973-2003.

With the incidence and prevalence of lymphoid neoplasms increasing, a comparison of survival patterns by subtype may provide critical clues for improving the disease burden. We conducted a comprehensive survival analysis for 254,702 lymphoid neoplasm cases diagnosed during 1973–2003 at 17 Surveillance, Epidemiology and End Results (SEER) registries according to the World Health Organization (WHO) classification introduced in 2001. The best survival was observed for Hodgkin lymphoma among young patients, and the worst survival was observed among cases with plasma cell neoplasms, particularly plasma cell leukemia, in all racial groups. Being diagnosed at a lower stage without B-symptoms and a non-HIV/AIDS status favored survival for each type of lymphoma. Males typically had lower survival rates than females, but the opposite was observed for Burkitt lymphoma/leukemia among non-whites and multiple myeloma among non-Hispanic whites. Non-Hispanic whites typically had higher survival rates than blacks with the exception of multiple myeloma. Survival rates decline with age at diagnosis among elders, while the patterns were diverse by subtype among younger cases. The differences in lymphoma survival patterns suggest that distinct prognostic risk factors impact survival by subtype and that future research and public health interventions should address racial disparities in lymphoma survivorship.

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study†

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health‐American Association of Retired Persons (NIH‐AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124‐item food frequency questionnaire. During an average of 7 years of follow‐up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29–4.041; p‐trend <0.001); however, we observed no trend with intake among women (p‐trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09–4.05; p‐trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03–11.4; p‐trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86–8.77; p‐trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.

Time trends in oral clefts in Chinese newborns: Data from the Chinese National Birth Defects Monitoring Network

BACKGROUND Although the prevalence of oral clefts in China is among the highest in countries worldwide, little is known about its descriptive epidemiology. METHODS Data used in this study were collected from 1996 to 2005 using the nationwide hospital-based registry, the Chinese Birth Defects Monitoring Network. A total of 4,891,472 newborns (live or still births with 28 weeks of gestation or more) delivered in member hospitals were assessed for birth defects within 7 days following birth. RESULTS The prevalence of nonsyndromic, syndromic, and overall clefts was 14.23, 2.40, and 16.63 per 10,000, respectively. An upward time trend in the prevalence of nonsyndromic cleft palate and nonsyndromic cleft lip was detected. Cleft lip with or without cleft palate showed a different pattern by gender, urban-rural classification, and geographic location when compared to cleft palate, particularly for nonsyndromic cases. Maternal age was associated with prevalence of all oral clefts. Neonates with oral clefts had increased rates of mortality. CONCLUSIONS The observed complex patterns of prevalence of oral clefts from the Chinese national birth defects registry indicate that oral cleft subtypes by either cleft location or syndromic status should be considered in the development of intervention measures and in future analytical studies.

Meat and components of meat and the risk of bladder cancer in the NIH‐AARP Diet and Health Study

Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat‐related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer.

Dietary Components Related to N-Nitroso Compound Formation: A Prospective Study of Adult Glioma

Background: N-nitroso compounds (NOC) are found in processed meat and are formed endogenously from intake of nitrite and nitrate. Endogenous NOC formation is antagonized by nitrosation inhibitors in fruit and vegetables (e.g., vitamin C) and promoted by heme in red meat. It has been hypothesized that a diet resulting in high exposure to NOCs increases adult glioma risk. Methods: Using proportional hazards models, we tested this hypothesis among 545,770 participants in the prospective NIH-AARP Diet and Health Study, which assessed dietary intake at baseline (1995–1996) with a comprehensive food frequency questionnaire, and at ages 12 to 13 years with an abbreviated food frequency questionnaire. Results: During follow-up through 2003, 585 participants were diagnosed with glioma. We found no significant trends in glioma risk for consumption of processed or red meat, nitrate, or vitamin C or E. We found significant positive trends for nitrite intake from plant sources (hazard ratio for quintile 5 versus quintile 1, 1.59; 95% confidence interval, 1.20–2.10; P for trend = 0.028) and, unexpectedly, for fruit and vegetable intake (hazard ratio, 1.42; 95% confidence interval, 1.08–1.86; P for trend = 0.0081). Examination of interactions between dietary intakes (e.g., nitrite and vitamin C) and a limited analysis of diet at ages 12 to 13 years provided no support for the NOC hypothesis. Conclusions: Our results suggest that consumption of processed or red meat, nitrite, or nitrate does not increase adult glioma risk, and that consumption of fruit and vegetables, vitamin C, or vitamin E does not reduce risk. Impact: Our results, in agreement with the only previous prospective analysis, cast doubt on the NOC hypothesis in relation to dietary intake and adult glioma risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1709–22. ©2010 AACR.

COL1A2 gene polymorphisms (Pvu II and Rsa I), serum calciotropic hormone levels, and dental fluorosis

OBJECTIVES To investigate the relationship between dental fluorosis, polymorphisms in the COL1A2 gene, and serum calciotropic hormone levels. METHODS We conducted a case-control study among children between 8 and 12 years of age with (n = 75) and without (n = 165) dental fluorosis in two counties in Henan Province, China. The PvuII and RsaI polymorphisms in the COL1A2 gene were genotyped using the PCR-RFLP procedure. Calcitonin and osteocalcin levels in the serum were measured using radioimmunassays. RESULTS Children carrying the homozygous genotype PP of COL1A2 PvuII had a significantly increased risk of dental fluorosis (OR =4.85, 95% CI: 1.22-19.32) compared to children carrying the homozygous genotype pp in an endemic fluorosis village (EFV). However, the risk (OR = 1.07, 95% CI: 0.45-2.52) was not elevated when the control population was recruited from a non-endemic fluorosis village. Additionally, fluoride levels in urine and osteocalcin levels in serum were found to be significantly lower in controls from non-endemic villages compared to cases. However, the differences in fluoride and osteocalcin levels were not observed when cases were compared to a control population from endemic fluorosis villages. CONCLUSIONS This study provides the first evidence of an association between polymorphisms in the COL1A2 gene with dental fluorosis in high fluoride exposed populations. Future studies are needed to confirm the association.