Kidney Cancer Incidence Among Non-Hispanic American Indian and Alaska Native Populations in the United States, 1999-2020.

Background Non-Hispanic American Indian and Alaska Native (NH-AI/AN) people experience a disproportionate incidence of kidney cancer. Nationally aggregated data does not allow for a comprehensive description of regional disparities in kidney cancer incidence among NH-AI/AN communities. This study describes kidney cancer incidence rates and trends among NH-AI/AN compared to non-Hispanic White (NHW) populations by geographic region. Methods Using the United States Cancer Statistics American Indian and Alaska Native (AI/AN) Incidence Analytic Database, we calculated age-adjusted incidence rates (per 100,000) of kidney cancers for NH-AI/AN and NHW people for the years 2011-2020 combined using SEER*stat software. Analyses were restricted to non-Hispanic persons living in purchased/referred care delivery area (PRCDA) counties. Average annual percent changes (AAPCs) and trends (1999-2019) were estimated using Joinpoint regression analyses. Results Rates of kidney cancer incidence were higher among NH-AI/AN compared to NHW persons in the U.S. overall and in 5 of 6 regions. Kidney cancer incidence rates also varied by region, sex, age, and stage of diagnosis. Between 1999 and 2019, trends in rates of kidney cancer significantly increased among NH-AI/AN males (AAPC = 2.7%) and females (AAPC = 2.4%). The largest increases in incidence were observed for NH-AI/AN males and females under age 50 and those diagnosed with localized stage disease. Conclusions Study findings highlight growing disparities in kidney cancer incidence rates between NH-AI/AN and NHW populations. Impact: Differences in geographic region, sex, and stage highlight opportunities to decrease prevalence of kidney cancer risk factors and improve access to preventive care.

Incidence of Stomach, Liver, and Colorectal Cancers by Geography and Social Vulnerability Among American Indian and Alaska Native Populations, 2010-2019.

Social determinants of health and associated systems, policies, and practices are important drivers of health disparities. American Indian and Alaska Native (AI/AN) populations in the United States have elevated incidence rates of stomach, liver, and colorectal cancers compared with other racial/ethnic groups. In this study, we examined incidence rates of 3 types of gastrointestinal cancer among non-Hispanic AI/AN (NH-AI/AN) and non-Hispanic White (NHW) populations by geographic region and Social Vulnerability Index (SVI) score. Incident cases diagnosed during 2010-2019 were identified from population-based cancer registries linked with the Indian Health Service patient registration databases. Age-adjusted incidence rates (per 100,000 population) for stomach, liver, and colorectal cancers were compared within NH-AI/AN populations and between the NH-AI/AN and NHW populations by SVI score. Rates were higher among NH-AI/AN populations in moderate- and high-SVI-score counties in Alaska, the Southern Plains, and the East than in low-SVI counties. Incidence rates among NH-AI/AN populations were elevated when compared with NHW populations by SVI category. Results indicated that higher social vulnerability may drive elevated cancer incidence among NH-AI/AN populations. Additionally, disparities between NH-AI/AN and NHW populations persist even when accounting for SVI. Exploring social vulnerability can aid in designing more effective interventions to address root causes of cancer disparities among AI/AN populations.

Melanoma Incidence Rates Among Non-Hispanic American Indian/Alaska Native Individuals, 1999-2019.

Importance: Non-Hispanic American Indian/Alaska Native people have the second highest incidence rate of invasive cutaneous melanoma in the US after non-Hispanic White people. Objective: To examine invasive cutaneous melanoma incidence rates and trends over time among non-Hispanic American Indian/Alaska Native people. Design, Setting, and Participants: This descriptive, observational cross-sectional study used population-based cancer registry data (US Cancer Statistics AI/AN Incidence Analytic Database) linked to the Indian Health Service administrative database to examine incidence rates by age, sex, region, histology, tumor site, stage, and other demographic and clinical characteristics. The study examined trends from 1999 to 2019 time period by age, sex, stage at diagnosis, and region. Non-Hispanic American Indian/Alaska Native people 15 years and older who received a diagnosis of invasive cutaneous melanoma from 1999 to 2019 who were members of federally recognized tribes and resided in Indian Health Service purchased/referred care delivery areas were included in this study to reduce racial misclassification and provide more accurate rates. The data were analyzed in 2022. Exposures: Demographic and clinical characteristics, such as age, sex, geographic region, histology, stage, and tumor site. Main Outcomes and Measures: Invasive cutaneous melanoma incidence rates by age group, sex, region, resident county characteristics (poverty level, rurality, education level, and socioeconomic status), stage at diagnosis, tumor site, and histology. Trends over time by age, sex, region, and stage. Results: From 1999 to 2019, 2151 non-Hispanic American Indian/Alaska Native people (1021 female individuals [47.5%]) received a diagnosis of incident cutaneous melanoma (rate, 10.7 per 100 000; 95% CI, 10.3-11.2). Rates were higher among male than female individuals (13.0 [95% CI, 12.2-13.8] vs 9.2 [95% CI, 8.6-9.8]) and for people 55 years and older (24.2; 95% CI, 22.8-25.7) compared with those aged 15 to 39 years (3.5; 95% CI, 3.2-3.9). Rates were highest for male individuals 55 years and older (34.5; 95% CI, 31.8-37.3) and people living in the Southern Plains (male individuals: 23.8; 95% CI, 21.5-26.2; female individuals: 15.5; 95% CI, 14.0-17.2) and Pacific Coast region (male individuals: 16.5; 95% CI, 14.5-18.7; female individuals: 12.3; 95% CI, 10.9-13.9). Rates increased among female individuals from 1999 to 2019 (average annual percent change [AAPC], 2.5; P < .001); among regional/distant stage tumors (AAPC, 2.5; P = .01) and people 55 years and older (AAPC, 2.8; P = .001). Conclusions and Relevance: The results of this study suggest that additional studies could potentially identify risk factors among non-Hispanic American Indian/Alaska Native people.

Disparities in incidence and trends of colorectal, lung, female breast, and cervical cancers among non-Hispanic American Indian and Alaska Native people, 1999-2018.

PURPOSE: This study is the first to comprehensively describe incidence rates and trends of screening-amenable cancers (colorectal, lung, female breast, and cervical) among non-Hispanic AI/AN (NH-AI/AN) people. METHODS: Using the United States Cancer Statistics AI/AN Incidence Analytic Database, we, calculated incidence rates for colorectal, lung, female breast, and cervical cancers for NH-AI/AN and non-Hispanic White (NHW) people for the years 2014-2018 combined. We calculated age-adjusted incidence rates (per 100,000), total percent change in incidence rates between 1999 and 2018, and trends over this time-period using Joinpoint analysis. Screening prevalence by region was calculated using Behavioral Risk Factor Surveillance System data. RESULTS: Rates of screening-amenable cancers among NH-AI/AN people varied by geographic region and age at diagnosis. Over half of all lung and colorectal cancers in NH-AI/AN people were diagnosed at later stages. Rates of lung and colorectal cancers decreased significantly between 1999-2018 among NH-AI/AN men, but no significant changes were observed in rates of screening-amenable cancers among NH-AI/AN women. CONCLUSION: This study highlights disparities in screening-amenable cancers between NH-AI/AN and NHW people. Culturally informed, community-based interventions that increase access to preventive health services could reduce cancer disparities among AI/AN people.

Incidence of selected cancers in Non-Hispanic American Indian and Alaska Native adolescent and young adult populations, 1999-2019.

PURPOSE: Studies have highlighted geographic variation in cancer incidence rates among American Indian and Alaska Native (AI/AN) populations. This is the first study to comprehensively evaluate incidence rates and trends among non-Hispanic AI/AN (NH-AI/AN) adolescents and young adults (AYAs) ages 15-39 years. METHODS: Using the United States Cancer Statistics AI/AN Incidence Analytic Database, we identified all malignant cancer cases for NH-AI/AN AYA populations for the years 1999-2019. We calculated age-adjusted incidence rates (per 100,000) for NH-AI/AN populations overall, by region, and by age group. We calculated the total percent change in the incidence of leading AYA cancers between 1999 and 2019, and trends by region and cancer type using Joinpoint analysis. RESULTS: Testicular (13.6) and breast (19.0) cancers had the highest incidence of all AYA cancers in NH-AI/AN males and females, respectively. Overall AYA cancer rates increased by 1.4% in NH-AI/AN males and 1.8% in NH-AI/AN females annually between 1999 and 2019. Increases were observed by age group and geographic region. CONCLUSIONS: This study describes regional differences in incidence rates of AYA cancers among NH-AI/AN populations. This data can help inform resource and cancer control priorities and strategies to reduce cancer risk and enhance access to quality diagnostic and treatment services for this population.

Social Determinants of Cancer Risk Among American Indian and Alaska Native Populations: An Evidence Review and Map.

Objectives: To explore current literature on social determinants of health (SDOH) and cancer among American Indian and Alaska Native (AI/AN) populations. Methods: We searched Ovid MEDLINE®, CINAHL, and PsycINFO databases for articles published during 2000 to 2020, which included terms for SDOH and cancer occurrence in AI/AN populations. We derived the data extraction elements from the PROGRESS-Plus framework. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Equity extension guided the evidence map. Results: From 2180 screened articles, 297 were included. Most were observational (93.9%), employed a cross-sectional design (83.2%), were categorized as cancer occurrence and surveillance research (62%), and included no cancer-related risk factors (70.7%). Race, gender, and place were the most frequently included PROGRESS-Plus categories. Religion, relationship features, and characteristics of discrimination were least common. Only 12% of articles mentioned historical/current trauma or historical context. Conclusions: Gaps exist in our understanding of SDOH as drivers of cancer disparities in AI/AN populations. Future studies in health equity science may incorporate historical and cultural factors into SDOH frameworks tailored for AI/AN populations.

Cancer disparities among non-Hispanic urban American Indian and Alaska Native populations in the United States, 1999-2017.

BACKGROUND: Disparities in cancer incidence have not been described for urban American Indian/Alaska Native (AI/AN) populations. The purpose of the present study was to examine incidence rates (2008-2017) and trends (1999-2017) for leading cancers in urban non-Hispanic AI/AN (NH AI/AN) compared to non-Hispanic White (NHW) populations living in the same urban areas. METHODS: Incident cases from population-based cancer registries were linked with the Indian Health Service patient registration database for improved racial classification of NH AI/AN populations. This study was limited to counties in Urban Indian Health Organization service areas. Analyses were conducted by geographic region. Age-adjusted rates (per 100,000) and trends (joinpoint regression) were calculated for leading cancers. RESULTS: Rates of colorectal, liver, and kidney cancers were higher overall for urban NH AI/AN compared to urban NHW populations. By region, rates of these cancers were 10% to nearly 4 times higher in NH AI/AN compared to NHW populations. Rates for breast, prostate, and lung cancer were lower in urban NH AI/AN compared to urban NHW populations. Incidence rates for kidney, liver, pancreatic, and breast cancers increased from 2% to nearly 7% annually between 1999 to 2017 in urban NH AI/AN populations. CONCLUSIONS: This study presents cancer incidence rates and trends for the leading cancers among urban NH AI/AN compared to urban NHW populations for the first time, by region, in the United States. Elevated risk of certain cancers among urban NH AI/AN populations and widening cancer disparities highlight important health inequities and missed opportunities for cancer prevention in this population.

Growing Disparity in the Incidence of Colorectal Cancer among Non-Hispanic American Indian and Alaska Native Populations-United States, 2013-2017.

BACKGROUND: American Indian and Alaska Native (AI/AN) populations have experienced regional variation and disparities in colorectal cancer incidence rates. METHODS: We examined colorectal cancer incidence (2013-2017) and colorectal cancer incidence trends (1999-2017) among AI/AN persons. Incidence data were linked to Indian Health Service enrollment records, and analyses were restricted to Purchased/Referred Care Delivery Areas. Incidence rates of colorectal cancer among AI/AN and White persons were analyzed in six geographic regions; Hispanic persons were excluded. Incidence trends were analyzed using linear modeling. RESULTS: During 2013-2017, colorectal cancer incidence was 41% higher among AI/AN than among White persons. AI/AN incidence rates per 100,000 varied regionally from 34.4 in the East to 96.1 in Alaska. Compared with White persons, AI/AN persons had higher colorectal cancer incidence rates among all age strata and were more likely to have late-stage diagnoses. Incidence rate trends indicated significant increases among both AI/AN and White persons ages <50 years and among AI/AN persons ages 50-64 years. The colorectal cancer incidence rate trend increased among AI/AN persons in the Southwest. CONCLUSIONS: The disparity of colorectal cancer incidence rates between AI/AN and White persons has widened since 2005-2009. AI/AN populations have higher colorectal cancer incidence compared with White populations, especially in the Alaska region. IMPACT: Our finding of increased colorectal cancer incidence disparities suggests that enhanced screening efforts and culturally appropriate clinical and public health interventions are needed among AI/AN persons overall, and especially in regions and age groups in which colorectal cancer rates are increasing.

Incidence of and Trends in the Leading Cancers With Elevated Incidence Among American Indian and Alaska Native Populations, 2012-2016.

Cancer incidence varies among American Indian and Alaska Native (AI/AN) populations, as well as between AI/AN and White populations. This study examined trends for cancers with elevated incidence among AI/AN compared with non-Hispanic White populations and estimated potentially avoidable incident cases among AI/AN populations. Incident cases diagnosed during 2012-2016 were identified from population-based cancer registries and linked with the Indian Health Service patient registration databases to improve racial classification of AI/AN populations. Age-adjusted rates (per 100,000) and trends were calculated for cancers with elevated incidence among AI/AN compared with non-Hispanic White populations (rate ratio of >1.0) according to region. Trends were estimated using joinpoint regression analyses. Expected cancers were estimated by applying age-specific cancer incidence rates among non-Hispanic White populations to population estimates for AI/AN populations. Excess cancer cases among AI/AN populations were defined as observed minus expected cases. Liver, stomach, kidney, lung, colorectal, and female breast cancers had higher incidence rates among AI/AN populations across most regions. Between 2012 and 2016, nearly 5,200 excess cancers were diagnosed among AI/AN populations, with the largest number of excess cancers (1,925) occurring in the Southern Plains region. Culturally informed efforts could reduce cancer disparities associated with these and other cancers among AI/AN populations.

Cancers Associated with Human Papillomavirus in American Indian and Alaska Native Populations - United States, 2013-2017.

Human papillomavirus (HPV) causes most cervical cancers and some cancers of the penis, vulva, vagina, oropharynx, and anus. Cervical precancers can be detected through screening. HPV vaccination with the 9-valent HPV vaccine (9vHPV) can prevent approximately 92% of HPV-attributable cancers (1).* Previous studies have shown lower incidence of HPV-associated cancers in non-Hispanic American Indian and Alaska Native (AI/AN) populations compared with other racial subgroups (2); however, these rates might have been underestimated as a result of racial misclassification. Previous studies have shown that cancer registry data corrected for racial misclassification resulted in more accurate cancer incidence estimates for AI/AN populations (3,4). In addition, regional variations in cancer incidence among AI/AN populations suggest that nationally aggregated data might not adequately describe cancer outcomes within these populations (5). These variations might, in part, result from geographic disparities in the use of health services, such as cancer screening or vaccination (6). CDC analyzed data for 2013-2017 from central cancer registries linked with the Indian Health Service (IHS) patient registration database to assess the incidence of HPV-associated cancers and to estimate the number of cancers caused by HPV among AI/AN populations overall and by region. During 2013-2017, an estimated 1,030 HPV-associated cancers were reported in AI/AN populations. Of these cancers, 740 (72%) were determined to be attributable to HPV types targeted by 9vHPV; the majority were cervical cancers in females and oropharyngeal cancers in males. These data can help identify regions where AI/AN populations have disproportionately high rates of HPV-associated cancers and inform targeted regional vaccination and screening programs in AI/AN communities.

Gastric Cancer Among American Indian and Alaska Native Populations in the United States, 2005-2016.

INTRODUCTION: American Indian and Alaska Native (AI/AN) populations have higher gastric cancer rates than the general US population. This study provides a comprehensive overview of incidence rates among AI/AN persons during 2005-2016 compared with non-Hispanic whites (whites). METHODS: Population-based cancer registry data for 2005-2016 were linked with the Indian Health Service patient registration databases to address racial misclassification. Age-adjusted gastric cancer incidence rates were expressed per 100,000 per year. Incidence and trend analyses were restricted to purchased/referred care delivery area counties in 6 geographic regions, comparing gastric cancer incidence rates for AI/AN vs white populations in the United States. RESULTS: Gastric cancer rates were higher in the AI/AN compared with white populations in nearly every US region. Incidence rates for central/distal portions of the stomach were higher in AI/AN individuals compared with whites. Rates of later stage gastric cancer were higher in AI/AN populations overall and in every region except the Pacific Coast and East. Incidence rates decreased significantly over time in both populations. Declining rates in the AI/AN populations were driven by changes in the Pacific Coast and Northern Plains regions. DISCUSSION: AI/AN populations have a disproportionately high incidence of gastric cancer, especially in Alaska. High incidence in the central/distal portions of the stomach among AI/AN populations likely reflects a high prevalence of Helicobacter pylori infection in these populations. These data can be used to develop interventions to reduce risk factors and improve access to health services among AI/AN people at high risk for gastric cancer.

Disparities in Cancer Incidence and Trends among American Indians and Alaska Natives in the United States, 2010-2015.

BACKGROUND: Cancer incidence rates for American Indian and Alaska Native (AI/AN) populations vary by geographic region in the United States. The purpose of this study is to examine cancer incidence rates and trends in the AI/AN population compared with the non-Hispanic white population in the United States for the years 2010 to 2015. METHODS: Cases diagnosed during 2010 to 2015 were identified from population-based cancer registries and linked with the Indian Health Service (IHS) patient registration databases to describe cancer incidence rates in non-Hispanic AI/AN persons compared with non-Hispanic whites (whites) living in IHS purchased/referred care delivery area counties. Age-adjusted rates were calculated for the 15 most common cancer sites, expressed per 100,000 per year. Incidence rates are presented overall as well as by region. Trends were estimated using joinpoint regression analyses. RESULTS: Lung and colorectal cancer incidence rates were nearly 20% to 2.5 times higher in AI/AN males and nearly 20% to nearly 3 times higher in AI/AN females compared with whites in the Northern Plains, Southern Plains, Pacific Coast, and Alaska. Cancers of the liver, kidney, and stomach were significantly higher in the AI/AN compared with the white population in all regions. We observed more significant decreases in cancer incidence rates in the white population compared with the AI/AN population. CONCLUSIONS: Findings demonstrate the importance of examining cancer disparities between AI/AN and white populations. Disparities have widened for lung, female breast, and liver cancers. IMPACT: These findings highlight opportunities for targeted public health interventions to reduce AI/AN cancer incidence.

Incidence of primary liver cancer in American Indians and Alaska Natives, US, 1999-2009.

PURPOSE: To evaluate liver cancer incidence rates and risk factor correlations in non-Hispanic AI/AN populations for the years 1999-2009. METHODS: We linked data from 51 central cancer registries with the Indian Health Service patient registration databases to improve identification of the AI/AN population. Analyses were restricted to non-Hispanic persons living in Contract Health Service Delivery Area counties. We compared age-adjusted liver cancer incidence rates (per 100,000) for AI/AN to white populations using rate ratios. Annual percent changes (APCs) and trends were estimated using joinpoint regression analyses. We evaluated correlations between regional liver cancer incidence rates and risk factors using Pearson correlation coefficients. RESULTS: AI/AN persons had higher liver cancer incidence rates than whites overall (11.5 versus 4.8, RR = 2.4, 95% CI 2.3-2.6). Rate ratios ranged from 1.6 (Southwest) to 3.4 (Northern Plains and Alaska). We observed an increasing trend among AI/AN persons (APC 1999-2009 = 5%). Rates of distant disease were higher in the AI/AN versus white population for all regions except Alaska. Alcohol use (r = 0.84) and obesity (r = 0.79) were correlated with liver cancer incidence by region. CONCLUSIONS: Findings highlight disparities in liver cancer incidence between AI/AN and white populations and emphasize opportunities to decrease liver cancer risk factor prevalence.

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer.

Cohort study of oncologic emergencies in patients with head and neck cancer.

BACKGROUND: Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation. METHODS: We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time. RESULTS: History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations. CONCLUSION: Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.

Glycemic Index, Glycemic Load, and Lung Cancer Risk in Non-Hispanic Whites.

BACKGROUND: Postprandial glucose (PPG) and insulin responses play a role in carcinogenesis. We evaluated the association between dietary glycemic index (GI) and glycemic load (GL), markers of carbohydrate intake and PPG, and lung cancer risk in non-Hispanic whites. METHODS: GL and GI were assessed among 1,905 newly diagnosed lung cancer cases recruited from the University of Texas MD Anderson Cancer Center (Houston, TX) and 2,413 healthy controls recruited at Kelsey-Seybold Clinics (Houston, TX). We assessed associations between quintiles of GI/GL and lung cancer risk and effect modification by various risk factors. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression. RESULTS: We observed a significant association between GI [5th vs. 1st quintile (Q) OR = 1.49; 95% CI, 1.21-1.83; P(trend) <0.001] and lung cancer risk and GI(ac) (5th vs. 1st Q OR = 1.48; 95% CI, 1.20-1.81; P(trend) = 0.001) and lung cancer risk. We observed a more pronounced association between GI and lung cancer risk among never smokers (5th vs. 1st Q OR = 2.25; 95% CI, 1.42-3.57), squamous cell carcinomas (SCC; 5th vs. 1st Q OR = 1.92; 95% CI, 1.30-2.83), and those with less than 12 years of education (5th vs. 1st Q OR = 1.75; 95% CI, 1.19-2.58, P(interaction) = 0.02). CONCLUSION: This study suggests that dietary GI and other lung cancer risk factors may jointly and independently influence lung cancer etiology. IMPACT: Understanding the role of GI in lung cancer could inform prevention strategies and elucidate biologic pathways related to lung cancer risk.

Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in the etiology of renal cell carcinoma.

BACKGROUND: Meat-cooking mutagens may be associated with renal cell carcinoma (RCC) risk. In the current study, the authors examined associations between meat-cooking mutagens, genetic susceptibility variants, and risk of RCC. METHODS: The authors used 659 newly diagnosed RCC cases and 699 healthy controls to investigate the association between dietary intake of meat-cooking mutagens and RCC. They examined whether associations varied by risk factors for RCC and genetic susceptibility variants previously identified from genome-wide association studies. Odds ratios and 95% confidence intervals were estimated using tertiles of intake of dietary polycyclic aromatic hydrocarbons/heterocyclic amines. RESULTS: Dietary intake of the mutagenic compounds 2-amino-3,8-dimethylimidazo-(4,5-f) quinoxaline (MeIQx) and 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) were found to be significantly associated with an increased risk of RCC (odds ratios across tertiles: 1.00 [referent], 1.28 [95% confidence interval, 0.94-1.74], and 1.95 [95% confidence interval, 1.43-2.66] [P for trend <.001], respectively; and 1.00 [referent], 1.41 [95% confidence interval, 1.04-1.90], and 1.54 [95% confidence interval, 1.14-2.07] [P for trend =.02], respectively). The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06). CONCLUSIONS: The intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions.

Mitochondrial DNA copy number in peripheral blood leukocytes and the risk of clear cell renal cell carcinoma.

Variation of mitochondrial DNA copy number (mtDNAcn) in peripheral blood leukocytes has been associated with the risk of various cancers, including renal cell carcinoma (RCC). We assessed the association between mtDNAcn and clear cell RCC (ccRCC) risk in 608 cases and 629 controls frequency-matched on age and gender. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, body mass index, smoking status, history of hypertension, total energy intake and physical activity. Our results suggest an association between low mtDNAcn and ccRCC risk (OR = 1.28, 95% CI: 0.97-1.68, P = 0.09). Lower mtDNAcn was associated with increased ccRCC risk in younger individuals (age <60, OR = 1.68, 95% CI: 1.13-2.49, P = 0.01), women (OR = 1.66, 95% CI: 1.03-2.73, P = 0.04), individuals without history of hypertension (OR = 1.62, 95% CI: 1.09-2.41, P = 0.02) and individuals with low physical activity levels (OR = 1.55, 95% CI: 1.02-2.37, P = 0.05). We observed significant and marginally significant interactions between both age and history of hypertension and mtDNAcn in elevating ccRCC risk (P for interaction = 0.04 and 0.07, respectively). Additionally, low mtDNAcn was associated with ccRCC risk in younger individuals with low levels of physical activity [ORs and 95% CI for medium and low physical activity levels, respectively, 2.31 (1.18-4.52) and 2.09 (1.17-3.75), P interaction = 0.04]. To our knowledge, this is the first report to investigate the role of mtDNAcn in the ccRCC subtype and the first to suggest that this association may be modified by risk factors including age, gender, history of hypertension and physical activity.

Treatment of pediatric Grade II spinal ependymomas: a population-based study.

OBJECT: Grade II spinal cord ependymomas occurring in pediatric patients are exceptionally rare neoplasms. In this paper the authors use a national cancer database to determine patient demographics, treatment patterns, and associated outcomes of this cohort. METHODS: The Surveillance Epidemiology and End Results (SEER) database was used to analyze subjects younger than 18 years with histologically confirmed diagnoses of Grade II spinal cord ependymoma from the years 1973 to 2008. Descriptive data on the demographic characteristics of this cohort and the associated treatment patterns are shown. The Kaplan-Meier method was used to estimate overall survival at 1, 2, 5, and 10 years. RESULTS: This cohort comprised 64 pediatric subjects with Grade II spinal ependymoma. The median age was 13 years, nearly half of the patients were male, and most were white (84%). The median follow-up was 9.2 years. Overall survival at 5 and 10 years was 86% and 83%, respectively. Gross-total resection was achieved in 57% of subjects, and radiation therapy was administered to 36%. Radiation therapy was administered to 78% of subjects after subtotal resection but only to 19% of patients after gross-total resection; this difference was significant (p < 0.001). In a multivariate regression model analyzing sex, age at diagnosis, year of diagnosis, radiotherapy, and extent of resection, female sex was found to be an independent predictor of decreased mortality (HR 0.15 [95% CI 0.02-0.94], p = 0.04). CONCLUSIONS: These data show long-term outcomes for pediatric patients with Grade II spinal ependymoma. Radiotherapy was more likely to be administered in cases of subtotal resection than in cases of gross-total resection. Female sex is associated with decreased mortality, while other demographic or treatment modalities are not.