Early effects of low dose C ion or x-ray irradiation on peripheral blood lymphocytes of patients with alimentary tract cancer.

The aim of this study was to examine the early effects of low dose (12)C(6+) irradiation or X-ray on peripheral blood lymphocytes (PBL) of patients with alimentary tract cancer and to explore mechanisms that may be involved in an antitumor immune response. We found that the percentage of T lymphocyte subsets, the mRNA expression levels of IL-2 and IFN-γ in PBL, and their protein levels in supernatant were significantly increased 24 hours after exposure to low dose radiation. The effects were more pronounced in the group receiving 0.05Gy (12)C(6+) ion irradiation than the group receiving X-ray irradiation. There was no significant change in the percentage of NK cell subsets and TNF-α production of PBL. Our study suggests that low dose irradiation could alleviate immune suppression caused by tumor burden and that the effect was more pronounced for 0.05Gy high linear energy transfer (LET) (12)C(6+) irradiation.

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.

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

BACKGROUND: 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. METHODS: During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11). CONCLUSIONS: These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis.

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 >or=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.

Risk of non-Hodgkin lymphoma and nitrate and nitrite from the diet in Connecticut women.

It has been estimated that 65,980 individuals were diagnosed with non-Hodgkin lymphoma (NHL) and 19,500 died from NHL in the United States in 2009. Although established risk factors such as immunodeficiency and viral infections may be responsible for a portion of the cases, the majority of NHL cases remain unexplained. Dietary nitrate and nitrite intake are exposures of particular interest for NHL risk as they are precursors in the endogenous formation of N-nitroso compounds, which cause lymphomas in animal studies. We investigated NHL risk overall and by histologic type in relation to dietary nitrate and nitrite intake in a population-based case-control study of 1,304 women in Connecticut. Nitrate and nitrite intake were assessed using a 120-item food frequency questionnaire. We found no association between risk of NHL overall and dietary nitrate and a slightly increased risk of NHL with higher dietary nitrite intake (highest vs. lowest intake quartile OR = 1.4; 95% CI: 0.9-2.2). When we evaluated intake by subtype, a significant positive trend was observed for follicular lymphoma and nitrate (p-trend = 0.04) and nitrite (p-trend < 0.01) with an over twofold risk in the highest nitrite intake quartile (OR = 2.3; 95% CI: 1.1-4.9). An increased risk in the highest quartile of nitrite intake was also observed for T-cell lymphoma (OR = 3.4; 95% CI: 1.0-11.9). Animal products containing nitrite were more strongly associated with risk of follicular lymphoma; whereas, both animal and plant sources of nitrite were associated with elevated ORs for T-cell lymphoma. Our results confirm a previous finding for nitrite intake and NHL risk and highlight the importance of evaluating histologic type. We conclude that these results should be replicated in a larger study with data on drinking water as well as dietary sources of nitrate intake.

Genetic polymorphisms in cytochrome P450s, GSTs, NATs, alcohol consumption and risk of non-Hodgkin lymphoma.

The aim of this study was to investigate whether genetic polymorphisms in cytochrome P450s (CYPs), glutathione S-transferases (GSTs), and N-acetyltransferases (NATs) genes modify the relationship between alcohol consumption and risk of non-Hodgkin's lymphoma (NHL) in a population-based, case-control study including 1,115 Connecticut women. Although we did not find strong evidence that the genetic polymorphisms modify the relationship between alcohol consumption and risk of NHL, we identified significant interactions for multiple GSTs and NATs and alcohol intake among persons with DLBCL. Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL.

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.

Genetic variation in N-acetyltransferases 1 and 2, cigarette smoking, and risk of non-Hodgkin lymphoma.

Cigarette smoke contains many carcinogens that are metabolically activated through xenobiotic metabolism by phase I and II enzymes, including N-acetyltransferases 1 and 2 (NAT1 and NAT2). We investigated non-Hodgkin lymphoma risk in general and by subtype in relation to NAT1 and NAT2 genotypes and cigarette smoking in a population-based case-control study in Connecticut. Of the 535 controls, 53.1% reported ever smoking, and of the 461 cases, 55.7% reported ever smoking. We found a two-fold increased risk of T-cell lymphoma among those possessing the NAT1*10 genotype compared to those with other NAT1 genotypes; including an OR of 2.0 (95% CI: 1.0-2.4) for those heterozygous or homozygous for NAT1*10 genotypes. Rapid acetylator NAT2 phenotype increased the risk of both T-cell lymphoma (OR = 3.2; 95% CI: 1.1-9.5) and marginal zone lymphoma (OR = 3.0; 95% CI: 1.0-8.7), though these results were based on a small number of cases. When smoking status and risk of NHL was stratified by NAT1 and NAT2 genotypes, an increased risk of NHL overall was observed in current (OR = 1.7; 95% CI: 1.2-2.4) smokers without the NAT1*10 genotype but not among smokers with the NAT1*10 genotype (p-interaction < 0.01). No association between history of cigarette smoking and risk of NHL overall was observed with any NAT2 genotype. Our results present modest evidence that acetylation rate is associated with risk of NHL for specific subtypes and that the NAT1*10 genotype is an "at-risk" allele. Additionally, our results suggest that the relationship between NHL and smoking status may be modified by common genetic variation in NAT1 but not NAT2. We conclude that these findings require replication in larger studies and ultimately in pooled analyses.

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 Institute's 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.

Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma.

Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL.

Genetic polymorphisms in glutathione S-transferases and cytochrome P450s, tobacco smoking, and risk of non-Hodgkin lymphoma.

We investigated variation in glutathione S-transferases (GSTs) and cytochrome P450s (CYPs), and smoking in a population-based case-control study of NHL including 1,115 women. Although risk of NHL was not altered by variant polymorphisms in GSTs or CYPs, it was significantly changed for DLBCL when considered in conjunction with smoking behavior, though only in nonsmokers. An increased risk of DLBCL in nonsmokers was associated with the variant G allele for GSTP1 (OR = 1.6, 95% CI 1.0-2.3) and CYP1A1 (OR = 2.4; 95% CI 1.0-5.7), but a decreased risk for the variant G allele for CYP1B1 (OR = 0.6, 95% CI 0.4-1.0). Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL.

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 Institute's 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.

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.

Family history of malignancies and risk of breast cancer: prospective data from the Shanghai women's health study.

A population-based cohort study was conducted in Shanghai, China, to investigate the relationship between family cancer history in first-degree relatives and risk of breast cancer. A total of 570 newly diagnosed breast cancer patients were identified from the cohort of 73,222 women during the follow-up period. Breast cancer risk was elevated (RR = 1.74, 95% CI: 1.10-2.73) for those with a family history of breast cancer and the risk was stronger for women who were younger than 55 years (RR = 2.07, 95% CI: 1.17-3.64). In addition, a significantly increased risk was observed for women with a family history of leukemia (RR = 2.06; 95% CI: 1.02-4.15) and among younger women, those who reported having a family history of any cancer (RR = 1.41, 95% CI: 1.10-1.82), lung cancer (RR = 1.72, 95% CI: 1.12-2.65), and esophageal cancer (RR = 2.99, 95% CI: 1.62-5.51). This cohort study suggests that, as previously observed in high risk populations, family history plays an important role in breast cancer also in a low risk population. The link between breast cancer risk and family history of cancers of the lung and esophagus, as well as leukemia, warrants further investigation.

"Look at your health": outcomes associated with a computer-assisted smoking cessation counseling intervention for community college students.

Community college students represent 44% of all students enrolled in U.S. higher education facilities. To our knowledge, no previous smoking cessation intervention has targeted community college students. Previous studies suggest that a motivational smoking cessation intervention could be successful for young adult smokers. Combining motivational interviewing sessions with personalized health feedback is likely to increase participants' motivation to quit and movement through the stages of change. The purpose of this study was to evaluate the impact of a smoking cessation program based on these premises. We designed a computer-assisted, counselor-delivered smoking cessation program that addresses personal health risks and readiness to change smoking behavior among community college students. A group-randomized, controlled trial was used to assess the intervention in a sample of 426 students (58.5% females; mean age, 22.8+/-4.7 years) from 15 pair-matched campuses. At the 10-month follow-up assessment, the cotinine-validated smoking cessation rates were 16.6% in the experimental condition and 10.1% in the standard care condition (p=0.07). Our results indicate that our computer-assisted intervention holds considerable promise in reducing smoking among community college students.

Do Polybrominated Diphenyl Ethers (PBDEs) Increase the Risk of Thyroid Cancer?

An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAHs), particularly polybrominated diphenyl ethers (PBDEs), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDEs and other PHAHs increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAHs, particularly PBDEs, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDEs and other PHAHs. Such variation may result in different individual susceptibilities to PBDEs and other PHAHs and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDEs and other PHAHs in thyroid tumorigenesis and may provide a real means to prevent this deadly disease.

Tobacco control in state comprehensive cancer control plans: opportunities for decreasing tobacco-related disease.

INTRODUCTION: Comprehensive cancer control plans published by state, tribal, and territorial health agencies present an excellent opportunity to help prevent tobacco-related and other cancers. In this analysis, we sought to estimate the extent to which tobacco control activities outlined in state comprehensive cancer control plans incorporated the tobacco control recommendations presented by the Centers for Disease Control and Prevention (CDC) in Best Practices for Comprehensive Tobacco Control Programs-August 1999 (Best Practices) and The Guide to Community Preventive Services: Tobacco Use Prevention and Control (The Guide). METHODS: We analyzed the 39 available state comprehensive cancer control plans to determine which of the CDC tobacco control recommendations were incorporated. We then summarized these data across the 39 states. RESULTS: The 39 states incorporated a mean of 5.6 recommendations from Best Practices (SD, 2.8; range, 0-9) and 3.9 recommendations from The Guide (SD, 1.9; range, 0-6). Nearly one-half of state plans (48.7%) addressed funding for tobacco control; of these, 52.6% (25.6% of total) delineated a specific, measurable goal for funding. CONCLUSION: The extent to which tobacco control is addressed in state comprehensive cancer control plans varies widely. Our analysis revealed opportunities for states to improve compliance with CDC's tobacco-related recommendations for cancer control.

Pharmacy placement of nonprescription nicotine replacement therapy products and community pharmacists' counseling for product use.

OBJECTIVE: To investigate the relationship between nonprescription nicotine replacement therapy (NRT) product placement within community pharmacies and the number of patients whom pharmacists report counseling for use of these products. DESIGN: Cross-sectional study. SETTING: Four Northern California counties. PARTICIPANTS: 327 community pharmacists. INTERVENTIONS: Survey mailed in 1999-2000. MAIN OUTCOME MEASURES: Estimated number of NRT purchasers who received counseling in their pharmacy and pharmacists' level of control over NRT purchases and counseling as functions of the location of the NRT products within the pharmacy setting. RESULTS: Of 327 community pharmacists surveyed, 26 (8.0%) reported that all nonprescription NRT products were stocked behind the pharmacy counter (full control over NRT purchases and counseling), 46 (14.1%) reported that all NRT products were stocked outside of the pharmacy department in an area that could not be seen easily by the pharmacist (no control), and the remainder (n = 255; 78.0%) indicated that all NRT products were located within their visual field but not behind the counter and/or that NRT products were located in more than one of the three previously described store locations (i.e., behind counter, not behind counter but within visual field, and outside visual field) (partial control). While adjusting for known confounders (pharmacists' self-efficacy for counseling, practice setting, and perceived pros of counseling), NRT product location was significantly associated with counseling of four or more patients a month for use of these products (P = .005). Specifically, compared with pharmacists with no control over NRT purchases and counseling, pharmacists with full control were 4.73 (95% CI, 1.46-15.37) times as likely to counsel four or more patients per month, and pharmacists with partial control were 2.95 (95% CI, 1.47-5.94) times as likely. Compared with pharmacists with partial control, pharmacists with full control were 1.60 (95% CI, 0.58-4.41) times as likely to counsel at least four patients monthly (P = .361). CONCLUSION: The location of nonprescription NRT products within the community pharmacy setting is associated with the number of patients whom pharmacists report counseling for use of these products.

The epidemiology of tobacco use and dependence.

Tobacco use continues to be a public health issue of great importance. Acute and critical care nurses in particular have a unique opportunity to become a cornerstone for the nation's tobacco control efforts through integration of prevention and cessation interventions as part of patient care. This article provides readers with a working knowledge of tobacco use and dependence as background reading for the subsequent articles presented in this special issue addressing tobacco cessation in acute and critical care settings.