Aspirin use and head and neck cancer survival and recurrence.

BACKGROUND: Head and neck cancer (HNC) has low 5-year survival, and evidence-based recommendations for tertiary prevention are lacking. Aspirin improves outcomes for cancers at other sites, but its role in HNC tertiary prevention remains understudied. METHODS: HNC patients were recruited in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Aspirin data were collected through medical record review; outcomes (overall mortality, HNC-specific mortality, and recurrence) were collected through medical record review, Social Security Death Index, or LexisNexis. Cox proportional hazards models were used to evaluate the associations between aspirin use at diagnosis (yes/no) and HNC outcomes. RESULTS: We observed no statistically significant associations between aspirin and cancer outcome in our HNC patient cohort (n = 1161) (HNC-specific mortality: HR = 0.91, 95% CI = 0.68-1.21; recurrence: HR = 0.94, 95% CI = 0.73-1.19). In analyses stratified by anatomic site, HPV status, and disease stage, we observed no association in any strata examined with the possible exception of a lower risk of recurrence in oropharynx patients (HR = 0.60, 95% CI 0.35-1.04). CONCLUSIONS: Our findings do not support a protective association between aspirin use and cancer-specific death or recurrence in HNC patients, with the possible exception of a lower risk of recurrence in oropharynx patients.

Prostate cancer aggressiveness and financial toxicity among prostate cancer patients.

INTRODUCTION: Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10-15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT. METHODS: PCa patients enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were recontacted for long-term follow-up. The prevalence of FT in the PCaP cohort was estimated. FT was estimated using the COmprehensive Score for Financial Toxicity, a validated measure of FT. The direct effect of PCa aggressiveness and an indirect effect through current cancer treatment on FT was examined using causal mediation analysis. RESULTS: More than one-third of PCa patients reported experiencing FT. PCa aggressiveness was significantly independently associated with high FT; high aggressive PCa at diagnosis had more than twice the risk of experiencing FT than those with low or intermediate aggressive PCa (adjusted odds ratio [aOR] = 2.13, 95% CI = 1.14-3.96). The proportion of the effect of PCa aggressiveness on FT, mediated by treatment status, was 10%, however, the adjusted odds ratio did not indicate significant evidence of mediation by treatment status (aOR = 1.05, 95% CI = 0.95-1.20). CONCLUSIONS: Aggressive PCa was associated with high FT. Future studies should collect more information about the characteristics of men with high FT and identify additional risk factors of FT.

Socioeconomic Disparities in the Association Between All-Cause Mortality and Health Check-Up Participation Among Healthy Middle-Aged Workers: A Nationwide Study.

BACKGROUND: This study assessed the relationship between non-participation in health check-ups and all-cause mortality and morbidity, considering socioeconomic status. METHODS: Healthy, middle-aged (35-54 years) working individuals who maintained either self-employed or employee status from 2006-2010 were recruited in this retrospective cohort study from the National Health Insurance Service in Korea. Health check-up participation was calculated as the sum of the number of health check-ups in 2007-2008 and 2009-2010. Adjusted hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality were estimated for each gender using multivariable Cox proportional hazard models, adjusting for age, income, residential area, and employment status. Interaction of non-participation in health check-ups and employment status on the risk of all-cause mortality was further analyzed. RESULTS: Among 4,267,243 individuals with a median 12-year follow-up (median age, 44; men, 74.43%), 89,030 (2.09%) died. The proportion (number) of deaths of individuals with no, one-time, and two-time participation in health check-ups was 3.53% (n = 47,496), 1.66% (n = 13,835), and 1.33% (n = 27,699), respectively. The association between health check-up participation and all-cause mortality showed a reverse J-shaped curve with the highest adjusted HR (95% CI) of 1.575 (1.541-1.611) and 1.718 (1.628-1.813) for men and women who did not attend any health check-ups, respectively. According to the interaction analysis, both genders showed significant additive and multiplicative interaction, with more pronounced additive interaction among women who did not attend health check-ups (relative excess risk due to interaction, 1.014 [0.871-1.158]). CONCLUSION: Our study highlights the significant reverse J-shaped association between health check-up participation and all-cause mortality. A pronounced association was found among self-employed individuals, regardless of gender.

Racial and ethnic disparities in nasopharyngeal cancer with an emphasis among Asian Americans.

Despite the overall decreasing incidence, nasopharyngeal cancer (NPC) continues to cause a significant health burden among Asian Americans (AAs), who are a fast-growing but understudied heterogeneous racial group in the United States. We aimed to examine the racial/ethnic disparities in NPC incidence, treatment, and mortality with a specific focus on AA subgroups. NPC patients aged ≥15 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) 18 (1975-2018). AAs were divided into Chinese, Filipino, Vietnamese, Hawaiian, Japanese, Laotian, Korean, Cambodian, Indian/Pakistani and other Asian/Pacific Islanders (APIs). Age-adjusted incidence was calculated using the SEER*Stat software. Cox proportional and Fine-Gray subdistribution hazard models were used to calculate overall and cause-specific mortalities after adjusting for confounders. Among the total 11 964 NPC cases, 18.4% were Chinese, 7.7% Filipino, 5.0% Vietnamese, 1.2% Hawaiian, 1.0% Japanese, 0.8% Laotian, 0.8% Korean, 0.6% Cambodian, 0.5% Indian/Pakistani and 4.4% other APIs. Laotians had the highest age-adjusted NPC incidence (9.21 per 100 000), which was 18.04 times higher than it in non-Hispanic Whites (NHWs). Chinese and Filipinos observed lower overall mortalities, however, Chinese saw increased NPC-specific mortality than NHWs. Disparities in mortality were also found across different histology subtypes. This is the first and largest study examining the NPC incidence and outcomes in AA subgroups. The significant disparities of NPC within AAs underline the importance of adequate AA-subgroup sample size in future studies to understand the prognostic role of ethnicity in NPC and advocate more ethnically and culturally tailored cancer prevention and care delivery.

Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study.

BACKGROUND: The overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer-specific mortality exist. The neighborhood-level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors. METHODS: North Carolina-Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all-cause and PCa-specific mortality adjusted for age, race, study site, insurance status, and comorbidities. RESULTS: Participants living in the most deprived neighborhoods had an increased risk for all-cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16-1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer-specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10-3.50) than those in the least deprived neighborhood. CONCLUSIONS: The findings suggest neighborhood-level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality.

Risk of Disease Recurrence and Mortality Varies by Type of Fat Consumed before Cancer Treatment in a Longitudinal Cohort of Head and Neck Squamous Cell Carcinoma Patients.

BACKGROUND: The associations between specific types of fat and head and neck squamous cell carcinoma (HNSCC) recurrence and mortality rates have not yet been examined. OBJECTIVES: The purpose of this study was to determine how intakes of various fat subtypes before cancer treatment are associated with recurrence and mortality in adults diagnosed with HNSCC. METHODS: This was a secondary analysis longitudinal cohort study of data collected from 476 newly diagnosed patients with HNSCC. Patients completed baseline FFQs and epidemiologic health surveys. Recurrence and mortality events were collected annually. Fat intakes examined included long-chain fatty acids (LCFAs), unsaturated fatty acids (FAs), PUFAs, ω-3 (n-3) PUFAs, ω-6 (n-6) PUFAs, MUFAs, animal fats, vegetable fats, saturated FAs, and trans fats. Associations between fat intake (categorized into tertiles) and time to event were tested using multivariable Cox proportional hazards models, adjusting for age, sex, smoking status, human papillomavirus status, tumor site, cancer stage, and total caloric intake. Intake of fats was compared with the lowest tertile. RESULTS: During the study period, there were 115 recurrent and 211 death events. High LCFA intake was associated with a reduced all-cause mortality risk (HR: 0.55; 95% CI: 0.34, 0.91; P-trend = 0.02). High unsaturated FA intake was associated with a reduced all-cause mortality risk (HR: 0.62; 95% CI: 0.40, 0.97; P-trend = 0.04) and HNSCC-specific mortality risk (HR: 0.51; 95% CI: 0.29, 0.90; P-trend = 0.02). High intakes of ω-3 PUFAs (HR: 0.56; 95% CI: 0.35, 0.91; P-trend = 0.02) and ω-6 PUFAs (HR: 0.57; 95% CI: 0.34, 0.94; P-trend = 0.02) were significantly associated with a reduced all-cause mortality risk. There were no significant associations between other fat types and recurrence or mortality risk. CONCLUSIONS: In this prospective survival cohort of 476 newly diagnosed patients with HNSCC, our data suggest that HNSCC prognosis may vary depending on the fat types consumed before cancer treatment. Clinical intervention trials should test these associations.

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors.

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors' responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55-41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02-21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

Association between global DNA methylation (LINE-1) and occupational particulate matter exposure among informal electronic-waste recyclers in Ghana.

This study examined the associations between PM (2.5 and 10) and global DNA methylation among 100 e-waste workers and 51 non-e-waste workers serving as controls. Long interspersed nucleotide repetitive elements-1 (LINE-1) was measured by pyrosequencing. Personal PM2.5 and PM10 were measured over a 4-hour work-shift using real-time particulate monitors incorporated into a backpack . Linear regression models were used to assess the association between PM and LINE-1 DNA methylation. The concentrations of PM2.5 and PM10 were significantly higher among the e-waste workers than the controls (77.32 vs 34.88, p < 0.001 and 210.21 vs 121.92, p < 0.001, respectively). PM2.5 exposure was associated with increased LINE-1 CpG2 DNA methylation (ß = 0.003; 95% CI; 0.001, 0.006; p = 0.022) but not with the average of all 4 CpG sites of LINE-1. In summary, high levels of PM2.5 exposure was associated with increased levels of global DNA methylation in a site-specific manner.

Statin use and head and neck squamous cell carcinoma outcomes.

Head and neck squamous cell carcinoma (HNSCC) is a morbid cancer with poor outcomes. Statins possess anticancer properties such as immunomodulatory and anti-inflammatory effects. The objective of our study is to identify the association between statin use among untreated HNSCC patients and overall death, disease-specific death and recurrence. HNSCC patients were recruited to participate in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Statin use data were collected through medical record review. Participants were considered a statin user if they used a statin at or after diagnosis. Outcome data were collected through medical record review, Social Security Death Index or LexisNexis. Our analytic cohort included 1638 participants. Cox proportional hazard models were used to estimate the association between ever statin use and HNSCC outcomes. Statin use was seen in 36.0% of participants. We observed a statistically significant inverse association between ever using a statin and overall death (HR = 0.75, 95% CI = 0.63-0.88) and HNSCC-specific death (HR = 0.79, 95% CI = 0.63-0.99) and a nonstatistically significant inverse association for recurrence (HR = 0.85, 95% CI = 0.70-1.04). When investigating the association between statin use and HNSCC outcomes utilizing interaction terms between statin use and human papillomavirus (HPV), statistically significant interactions for HNSCC-specific death and recurrence were identified (HNSCC-specific death: HPV-positive HR = 0.41, 95% CI = 0.21-0.84; HPV-negative HR = 1.04, 95% CI = 0.71-1.51; p-int=0.02; recurrence: HPV-positive HR = 0.49, 95% CI = 0.29-0.84; HPV-negative HR = 1.03, 95% CI = 0.74-1.43; p=int-0.02). Statin use may be protective for adverse outcomes in HNSCC patients, particularly those with HPV-positive disease. If true, these findings could have a meaningful impact on tertiary prevention for this cancer.

Opium use and the risk of head and neck squamous cell carcinoma.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.

Pretreatment Dietary Patterns, Serum Carotenoids and Tocopherols Influence Tumor Immune Response in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Tumor infiltrating lymphocytes (TILs) aid in informing treatment for head and neck squamous cell carcinoma (HNSCC). Nevertheless, little is known about the role of diet on TILs. METHODS: Immunohistologic expression of CD4, CD8, CD68, CD103, CD104 and FOXP3 were assessed in tissue microarrays from 233 previously untreated HNSCC patients. Associations between these markers and pretreatment dietary patterns were evaluated using linear regression. Associations between baseline serum carotenoids, tocopherols and TILs were assessed using logistic regression. Cox models evaluated the association between diet and TILs on overall and recurrence-free survival. RESULTS: Consumption of a Western dietary pattern was associated with lower CD8+ and FOXP3+ infiltrates (p-value:0.03 and 0.02, respectively). Multivariable logistic regression models demonstrated significantly higher CD8+ (OR:2.21;p-value:0.001) and FOXP3+ (OR:4.26;p-value:<0.0001) among patients with high gamma tocopherol. Conversely, high levels of xanthophylls (OR:0.12;p-value:<0.0001), lycopene (OR:0.36;p-value:0.0001) and total carotenoids(OR:0.31;p-value: <0.0001) were associated with significantly lower CD68+. Among those with high CD4+ (HR:1.77;p-value:0.03), CD68+ (HR:2.42;p-value:0.004), CD103+ (HR:3.64;p-value:0.03) and FOXP3+ (HR:3.09;p-value:0.05), having a high Western dietary pattern increased the risk of overall mortality when compared to a low Western dietary pattern. CONCLUSION: Dietary patterns and serum carotenoids may play an important role in modifying TILs, and ultimately, outcome after diagnosis with HNSCC.

Global DNA (LINE-1) methylation is associated with lead exposure and certain job tasks performed by electronic waste workers.

OBJECTIVE: This study assessed the associations between blood and urine levels of toxic metals; cadmium (Cd) and lead (Pb), and methylation levels of the LINE-1 gene among e-waste and control populations in Ghana. METHODS: The study enrolled 100 male e-waste workers and 51 all-male non-e-waste workers or controls. The concentrations of Cd and Pb were measured in blood and urine using inductively coupled plasma mass spectrometry, while LINE1 methylation levels were assessed by pyrosequencing of bisulfite-converted DNA extracted from whole blood. Single and multiple metals linear regression models were used to determine the associations between metals and LINE1 DNA methylation. RESULTS: Blood lead (BPb) and urine lead (UPb) showed higher median concentrations among the e-waste workers than the controls (76.82 µg/L vs 40.25 µg/L, p ≤ 0.001; and 6.89 µg/L vs 3.43 µg/L, p ≤ 0.001, respectively), whereas blood cadmium (BCd) concentration was lower in the e-waste workers compared to the controls (0.59 µg/L vs 0.81 µg/L, respectively, p = 0.003). There was no significant difference in LINE1 methylation between the e-waste and controls (85.16 ± 1.32% vs 85.17 ± 1.11%, p = 0.950). In our single metal linear regression models, BPb was significantly inversely associated with LINE1 methylation in the control group (ßBPb = - 0.027, 95% CI - 0.045, - 0.010, p = 0.003). In addition, a weak association between BPb and LINE1 was observed in the multiple metals analysis in the e-waste worker group (ßBPb = - 0.005, 95% CI - 0.011, 0.000, p = 0.058). CONCLUSION: Continuous Pb exposure may interfere with LINE1 methylation, leading to epigenetic alterations, thus serving as an early epigenetic marker for future adverse health outcomes.

Increasing incidence of Epstein-Barr virus-related nasopharyngeal carcinoma in the United States.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) has been historically low in the United States. Although etiological factors differ by histological subtype, Epstein-Barr virus is accepted as the primary risk factor for nonkeratinizing NPC. In light of the changing epidemiology of viral-associated cancers, it is important to evaluate the temporal incidence of NPC in the United States. METHODS: Incidence and survival data from 1973 through 2015 were obtained from the Surveillance, Epidemiology, and End Results program. Stratified analyses were conducted to assess temporal trends in NPC by histological subtype, sex, and race. The data were analyzed using SAS and Joinpoint Regression Software to determine age-adjusted incidence rates, determine trends in the annual percent change, and calculate 5-year relative survival estimates and Kaplan-Meier curves. RESULTS: Although overall NPC incidence is decreasing in the United States, the nonkeratinizing differentiated subtype is starkly increasing, with an annual percent change of approximately 4% among white males (95% CI, 2.5%-5.2%), white females (95% CI, 1.9%-6.2%), and black males (95% CI, 2.0%, 5.7%); 2.7% among black females (95% CI, 0.8%, 4.6%); and 1.8% among women in the "other" race category (95% CI, 0.4%-3.3%). Racial disparities were noted, with 32% of nonkeratinizing NPC cases among blacks occurring before the age of 40 years. In addition, black males displayed consistently worse survival across all histological subtypes, whereas individuals in the "other" race category, particularly females, experienced the highest 5-year relative survival estimates. CONCLUSIONS: The current results indicate that the Epstein-Barr virus-related, differentiated NPC subtype is increasing across all sexes and races in the United States, with distinct incidence and survival disparities among blacks.

Micronutrient status and leukocyte telomere length in school-age Colombian children.

PURPOSE: Leukocyte telomere length (LTL) is a biomarker of inflammation and oxidative stress that predicts chronic disease risk. Nutritional factors are related to LTL in adulthood, but these associations are not well characterized in children. We examined whether micronutrient status biomarkers were associated with LTL in school-age children. METHODS: We conducted a cross-sectional study of 330 boys and 393 girls aged 5-12 years from Bogotá, Colombia. We quantified blood concentrations of hemoglobin, ferritin, zinc, vitamin A, folate, and vitamin B-12; and measured LTL using qPCR in DNA extracted from buffy coat. We estimated mean differences in LTL by quartiles of micronutrient status biomarkers and categories of relevant sociodemographic and anthropometric covariates with the use of linear regression. RESULTS: In girls, plasma vitamin B-12 was positively associated with LTL (adjusted LTL difference between extreme vitamin B-12 quartiles = 0.11; P, trend = 0.02). LTL was also positively associated with birth order in girls (P, trend = 0.02). In boys, LTL was not related to the micronutrient status biomarkers but, unexpectedly, it was positively associated with birth weight (P = 0.02), height-for-age Z score (P, trend = 0.01), and serum C-reactive protein (P, trend = 0.01). CONCLUSIONS: LTL is associated with vitamin B-12 status among girls. LTL is also associated with birth weight, height, and C-reactive protein in boys.

Germline Genetic Features of Young Individuals With Colorectal Cancer.

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) in individuals younger than 50 years is increasing. We sought to ascertain the proportion of young CRC cases associated with genetic predisposition. METHODS: We performed a retrospective study of individuals diagnosed with CRC at an age younger than 50 years, evaluated by the clinical genetics service at a single tertiary care cancer center from 1998 through 2015. We collected data on patient histories, tumor phenotypes, and results of germline DNA sequencing. For subjects with uninformative clinical evaluations, germline DNA samples were (re)sequenced using a research-based next-generation sequencing multigene panel. The primary outcome was identification of a pathogenic germline mutation associated with cancer predisposition. RESULTS: Of 430 young CRC cases, 111 (26%) had a first-degree relative with CRC. Forty-one of the subjects with CRC (10%) had tumors with histologic evidence for mismatch repair deficiency. Of 315 subjects who underwent clinical germline sequencing, 79 had mutations associated with a hereditary cancer syndrome and 21 had variants of uncertain significance. Fifty-six subjects had pathogenic variants associated with Lynch syndrome (25 with mutations in MSH2, 24 with mutations in MLH1, 5 with mutations in MSH6, and 2 with mutations in PMS2) and 10 subjects had pathogenic variants associated with familial adenomatous polyposis. Thirteen subjects had mutations in other cancer-associated genes (8 in MUTYH, 2 in SMAD4, 1 in BRCA1, 1 in TP53, and 1 in CHEK2), all identified through multigene panel tests. Among 117 patients with uninformative clinical evaluations, next-generation sequence analysis using a multigene panel detected actionable germline variants in 6 patients (5%). Only 43 of the 85 subjects with germline mutations associated with a hereditary cancer syndrome (51%) reported a CRC diagnosis in a first-degree relative. CONCLUSIONS: Approximately 1 in 5 individuals diagnosed with CRC at age younger than 50 years carries a germline mutation associated with cancer; nearly half of these do not have clinical histories typically associated with the identified syndrome. Germline testing with multigene cancer panels should be considered for all young patients with CRC.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.

AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Childhood cancer incidence and survival in Thailand: A comprehensive population-based registry analysis, 1990-2011.

BACKGROUND: Southeast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20-year period. METHODS: Cancer cases diagnosed in children ages 0-19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population-based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age-standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan-Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC). RESULTS: The ASR of all childhood cancers during the study period was 98.5 per million person-years with 91.0 per million person-years in 1990-2000 and 106.2 per million person-years in 2001-2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P < 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5-year survival for all childhood cancers significantly improved from 39.4% in 1990-2000 to 47.2% in 2001-2011 (P < 0.01). CONCLUSIONS: Both childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low- and middle-income countries can improve understanding of cancer etiology and pediatric health care disparities.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.

Differences in prostate tumor characteristics and survival among religious groups in Songkhla, Thailand.

BACKGROUND: The incidence and mortality from prostate cancer is expected to increase in the next decade in Thailand. Despite the perceived lower risk in this population vs. developed, western countries, it is becoming an important public health issue. Prostate cancer incidence varies between the most predominant religious groups in Thailand, Buddhists and Muslims. However limited data is available describing the prostate cancer survival in these two populations. Here we examine differences in prostate tumor characteristics and survival between Buddhists and Muslims in the province of Songkhla, Thailand. METHODS: 945 incident prostate cancer cases (1990-2014) from the population-based Songkhla Cancer Registry were used in this analysis. Age, grade, stage, and year at diagnosis were compared across religious groups, using Wilcoxon or Chi-square tests. Kaplan Meier methods were used to estimate the median survival time and 5-year survival probabilities. Cox proportional hazards models were used to estimate hazard ratios (HR) between religious groups and 95% confidence intervals (CI) for mortality in age-adjusted and fully-adjusted models. RESULTS: Prostate tumor characteristics, age, and year at diagnosis were similar across religious groups. The median survival time after diagnosis of prostate cancer was longer in Buddhists 3.8 years compared with Muslims 3.2 years (p = 0.08). The age-adjusted risk of death after prostate cancer diagnosis was higher in Muslims compared with Buddhists (HR: 1.31; 95%CI: 1.00, 1.72). After adjustment by stage and grade, results were slightly attenuated (HR: 1.27, 95%CI: 0.97, 1.67). CONCLUSION: Muslims have shorter survival after prostate cancer diagnosis than do Buddhists in Thailand. The reasons underlying this difference require additional investigation in order to design targeted interventions for both populations.

Breast Cancer Incidence Trends and Projections in Northeastern Thailand.

BACKGROUND: The northeast has the lowest incidence of breast cancer of all regions in Thailand, although national rates are increasing. The heterogeneity in subnational trends necessitates a comprehensive evaluation of breast cancer incidence trends and projections to provide evidence for future region-specific strategies that may be employed to attenuate this growing burden. METHODS: Joinpoint regression and age-period-cohort modeling were used to describe trends from 1988-2012. Data was projected from three separate models to provide a range of estimates of incidence to the year 2030 by age group. RESULTS: Age-standardized rates (ASRs) increased significantly for all women from 1995-2012 by 4.5% per year. Rates for women below age 50 increased by 5.1% per year, while women age 50 years and older increased by 6% per year from 1988-2012. Projected rates show that women age 50 years and older have the largest projected increase in ASRs by 2030 compared to younger women and all women combined. CONCLUSIONS: Breast cancer trends in Khon Kaen are presently lower than other regions but are expected to increase and become comparable to other regions by 2030, particularly for women ages 50 years and older.