Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Survival advantage of Asian metastatic prostate cancer patients treated with external beam radiotherapy over other races/ethnicities.

PURPOSE: To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. METHODS: We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. RESULTS: After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52-0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities. CONCLUSION: In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.

Do Histopathology and Clinical Outcomes of Breast Atypia Vary by Race/Ethnicity?

BACKGROUND: The clinical behavior of breast cancer varies by racial and ethnic makeup (REM), but the impact of REM on the clinical outcomes of breast atypia remains understudied. We examined the impact of REM on risk of underlying or subsequent carcinoma following a diagnosis of breast atypia. METHODS: In this retrospective, single-institution chart review, adult women diagnosed with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ) were stratified by REM. Regression modeling was used to estimate risk of underlying or subsequent carcinoma. RESULTS: We identified 539 patients with breast atypia, including 15 Hispanic (2.8%), 127 non-Hispanic black (23.6%), and 397 non-Hispanic white women (73.7%). Diagnoses included 75.1% atypical ductal hyperplasia (n = 405), 4.6% atypical lobular hyperplasia (n = 25), and 20.2% lobular carcinoma in situ (n = 109). Rates for each type of atypia did not vary by REM (P = 0.33). Of those with atypia on needle biopsy, the rate of underlying carcinoma at excision was 17.3%. After adjustment, REM was not associated with greater risk for carcinoma at excision (P = 0.41). Of those with atypia alone on surgical excision, the rate of a subsequent carcinoma diagnosis was 15.4% (median follow-up 49 mo). REM was not associated with a long-term risk for carcinoma (P = 0.37) or differences in time to subsequent carcinoma (log-rank P = 0.52). Chemoprevention uptake rates were low (10.6%), especially among Hispanic (0%) and non-Hispanic black (3.8%) patients (P = 0.01). CONCLUSIONS: Among patients with atypia, REM does not appear to influence type of histologic atypia, risk for carcinoma, or clinical outcome, despite differences in chemoprevention rates.

Moxifloxacin Labeling-Based Multiphoton Microscopy of Skin Cancers in Asians.

BACKGROUND AND OBJECTIVES: Although multiphoton microscopy (MPM) can visualize both cell and extracellular matrix (ECM) structures of the skin in high-contrast without exogenous labeling, label-free MPM is usually too slow to image clinically relevant large regions. A high-speed MPM method would be beneficial for evaluating clinical skin specimens by increasing the imaging area. In this study, moxifloxacin labeling-based MPM (moxifloxacin MPM) was characterized in various human skin cancer specimens. STUDY DESIGN/MATERIALS AND METHODS: Moxifloxacin ophthalmic solution was used for cell-labeling and MPM imaging was conducted afterwards. Moxifloxacin MPM was characterized in ex vivo normal human skin and skin cancer specimens in comparison with the label-free MPM and fluorescence confocal microscopy (FCM) using acridine orange as a labeling agent. Then, moxifloxacin MPM was applied to various ex vivo human skin cancer specimens including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dermatofibrosarcoma protuberans (DFSP). Results of moxifloxacin MPM were compared with bright-field clinical and histopathologic findings. RESULTS: Moxifloxacin MPM imaged both cells and collagen in the skin, similarly to label-free MPM, but with enhanced fluorescence intensities in cells and enhanced imaging speeds. Moxifloxacin MPM imaged cells in the skin similarly to acridine orange-based FCM. Moxifloxacin MPM of various human skin cancer specimens imaged their specific cellular features. The microscopic features detected in moxifloxacin MPM were confirmed with histological images. CONCLUSIONS: This observational pilot study demonstrated that moxifloxacin MPM could detect specific cellular features of various skin cancers in good correlation with histopathological images in Asian patients at the higher imaging speed than label-free MPM. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Hysterectomy-Corrected Uterine Corpus Cancer Incidence Trends and Differences in Relative Survival Reveal Racial Disparities and Rising Rates of Nonendometrioid Cancers.

PURPOSE: Uterine corpus cancer incidence rates have been projected to increase, a prediction often attributed to the obesity epidemic. However, correct estimation of these rates requires accounting for hysterectomy prevalence, which varies by race, ethnicity, and region. Here, we evaluated recent trends in hysterectomy-corrected rates by race and ethnicity and histologic subtype and estimated differences in relative survival by race and ethnicity, subtype, and stage. METHODS: We estimated hysterectomy prevalence from the Behavioral Risk Factor Surveillance System. Hysterectomy-corrected age-standardized uterine corpus cancer incidence rates from 2000 to 2015 were calculated from the SEER 18 registries. Incidence rates and trends were estimated separately by race and ethnicity, region, and histologic subtype. Five-year relative survival rates were estimated by race and ethnicity, histologic subtype, and stage. RESULTS: Hysterectomy-corrected incidence rates of uterine corpus cancer were similar among non-Hispanic whites and blacks and lower among Hispanics and Asians/Pacific Islanders. Endometrioid carcinoma rates were highest in non-Hispanic whites, whereas nonendometrioid carcinoma and sarcoma rates were highest in non-Hispanic blacks. Hysterectomy-corrected uterine corpus cancer incidence increased among non-Hispanic whites from 2003 to 2015 and among non-Hispanic blacks, Hispanics, and Asians/Pacific Islanders from 2000 to 2015. Overall incidence rates among non-Hispanic blacks surpassed those of non-Hispanic whites in 2007. Endometrioid carcinoma rates rose among non-Hispanic blacks, Hispanics, and Asians/Pacific Islanders but were stable among non-Hispanic whites; however, nonendometrioid carcinoma rates rose significantly among all women. Non-Hispanic blacks had the lowest survival rates, irrespective of stage at diagnosis or histologic subtype. CONCLUSION: Among all women, rates of nonendometrioid subtypes have been rising rapidly. Our analysis shows profound racial differences and disparities indicated by higher rates of nonendometrioid subtypes and poorer survival among non-Hispanic black women.

The contribution of interleukin-8 genotypes and expression to nasopharyngeal cancer susceptibility in Taiwan.

The incidence rate of nasopharyngeal cancer (nasopharyngeal carcinoma [NPC]) is much higher in Southeast Asia than in western countries. Interleukin-8 (IL-8), a chemokine produced by macrophages, epithelial cells, airway smooth muscle cells, and endothelial cells, is an important immuno-mediator in the development and progression of many types of cancer. Genetic variations in IL-8 have been associated with the risks of NPC and other cancers. In the current study, we evaluated the role of IL-8 in NPC at the levels of DNA, RNA, and protein in a Taiwanese population. First, in a case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of IL-8 T - 251A, C + 781T, C + 1633T, and A + 2767T polymorphisms with NPC risk were evaluated. Second, the NPC tissue samples were assessed for their IL-8 mRNA and protein expression by real-time quantitative reverse transcription polymerase chain reaction (PCR) and Western blotting, respectively. Regarding the IL-8 promoter T - 251A, the TA and AA genotypes were associated with significantly decreased risks of NPC compared with the wild-type TT genotype (adjusted odds ratio = 0.61 and 0.52, 95% confidence interval = 0.47-0.93 and 0.37-0.91, P = .0415 and .0289, respectively). The mRNA and protein expression levels for NPC tissues revealed no significant associations among the 20 NPC samples with different genotypes. These findings suggest that IL-8 may play an important role in the carcinogenesis of NPC in Taiwan.

Risk factors for breast cancer among Indian women: A case-control study.

BACKGROUND: Breast cancer is the most common malignancy among females all over the world. The incidence of breast cancer is persistently on the rise due to urbanization and lifestyle changes. Although various risk factors have been suggested for estimating the risk of developing breast cancer, most of these have been studied in the Western population. A better understanding of local characteristics of risk factors may help in devising locally effective prevention strategies for breast cancer. The primary objective of the study was to study the risk factors for carcinoma breast among Indian women. MATERIALS AND METHODS: This was a case-control study, conducted from January 2011 to December 2012, at a tertiary level teaching institution. A total of 100 patients of Indian origin, attending the General Surgery Department with carcinoma breast during this period were the cases. Controls were the blood relatives of patients with other diagnosed malignancies. RESULTS: The major risk factors for breast cancer are found to be age, diet, waist size, hip size, waist-hip ratio (WHR), body mass index, high-density lipoprotein cholesterol, triglyceride, more than three pregnancies, number of years of menstruation, atypical hyperplasia in the previous biopsy, and history of carcinoma in relatives. CONCLUSIONS: Waist size and WHR are the major risk factors for carcinoma of breast. Adequate exercise and weight control are the most effective lifestyle changes that can reduce the risk of developing breast cancer.

Preoperative Prognostic Factors After Liver Resection for Non-Colorectal, Non-Neuroendocrine Liver Metastases and Validation of the Adam Score in an Asian Population.

BACKGROUND: Historically, the benefit of liver resection for non-colorectal, non-neuroendocrine (NCNN) liver metastases has been controversial. This study aims to determine the preoperative prognostic factors of liver resection for NCNN liver metastases and validate the Adam score in an Asian population. METHODS: Consecutive patients who underwent liver resection for NCNN liver metastases were identified retrospectively from a prospective liver resection database of the single institution between 2001 and 2014. Univariate Cox regression models were used to identify associations with outcome variables. Recurrence-free interval and overall survival were determined using the Kaplan-Meier method and compared using log-rank test. RESULTS: Seventy-eight consecutive patients were identified, which met the study criteria. Univariate analysis demonstrated that adenocarcinoma histology of primary cancer, disease-free interval and number of nodules were significant predictors of survival. Four of the six components of Adam score were significant predictors of survival. These were the presence of extrahepatic metastases, R2 resection, disease-free interval and type of a primary tumour. The total Adam score was also a significant predictor of survival. CONCLUSION: Liver resection for NCNN liver metastases is a safe and viable treatment option in carefully selected patients. Significant preoperative prognostic factors include adenocarcinoma primary tumours, disease-free interval and number of nodules. The total Adam score was a good predictor of overall survival and can be used to risk stratify patients undergoing hepatic resection for NCNN liver metastases.

Stomach cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

BACKGROUND: Stomach cancer was a leading cause of cancer-related deaths early in the 20th century and has steadily declined over the last century in the United States. Although incidence and death rates are now low, stomach cancer remains an important cause of morbidity and mortality in black, Asian and Pacific Islander, and American Indian/Alaska Native populations. METHODS: Data from the CONCORD-2 study were used to analyze stomach cancer survival among males and females aged 15 to 99 years who were diagnosed in 37 states covering 80% of the US population. Survival analyses were corrected for background mortality using state-specific and race-specific (white and black) life tables and age-standardized using the International Cancer Survival Standard weights. Net survival is presented up to 5 years after diagnosis by race (all, black, and white) for 2001 through 2003 and 2004 through 2009 to account for changes in collecting Surveillance, Epidemiology, and End Results Summary Stage 2000 data from 2004. RESULTS: Almost one-third of stomach cancers were diagnosed at a distant stage among both whites and blacks. Age-standardized 5-year net survival increased between 2001 to 2003 and 2004 to 2009 (26.1% and 29%, respectively), and no differences were observed by race. The 1-year, 3-year, and 5-year survival estimates were 53.1%, 33.8%, and 29%, respectively. Survival improved in most states. Survival by stage was 64% (local), 28.2% (regional), and 5.3% (distant). CONCLUSIONS: The current results indicate high fatality for stomach cancer, especially soon after diagnosis. Although improvements in stomach cancer survival were observed, survival remained relatively low for both blacks and whites. Primary prevention through the control of well-established risk factors would be expected to have the greatest impact on further reducing deaths from stomach cancer. Cancer 2017;123:4994-5013. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Impact of marital status at diagnosis on survival and its change over time between 1973 and 2012 in patients with nasopharyngeal carcinoma: a propensity score-matched analysis.

The impact of marital status at diagnosis on survival outcomes and its change over time in patients with nasopharyngeal carcinoma (NPC) are unclear. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with NPC in the United States from 1973 to 2012. A primary comparison (married vs. unmarried) was implemented with 1:1 propensity score matching. Secondary comparisons were performed individually between three unmarried subgroups (single, separated/divorced, widowed) and married group. The effect of marital status on cause-specific survival (CSS) and overall survival (OS) were evaluated using univariate/multivariate analysis. Moreover, we investigated the change over time (1973-2012) in the effect of marital status on NPC survival. Married patients had better 5-year CSS/OS than unmarried patients (61.1% vs. 52.6%, P < 0.001; 55.6% vs. 45.3%, P < 0.001, respectively). In multivariate analysis, unmarried patients had significantly poorer CSS/OS than married patients (adjusted hazard ratio [aHR] = 1.35, P < 0.001; aHR = 1.40, P < 0.001, respectively). The survival benefit of being married was only detected in non-Hispanic white and Chinese American patients. Single, separated/divorced, and widowed patients had significantly poorer CSS/OS than married patients (aHR = 1.37 and 1.37; 1.46 and 1.42; 1.43 and 1.48, respectively; all P < 0.001). The change over time in the effect of marital status on survival was more stable in male than female. The strength of the negative effect of separated/divorced and widowed status showed a downward and upward trend, respectively. Gender difference in the adverse effect of single status on NPC survival became smaller over time. Only non-Hispanic white and Chinese American patients with NPC obtain survival benefits from married status. Single and widowed patients are regarded as high-risk population.

Association of Single-Nucleotide Polymorphisms in DC-SIGN with Nasopharyngeal Carcinoma Susceptibility.

The aim of this study was to explore potential relationships of four single-nucleotide polymorphisms (SNPs) in the gene encoding dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) with risk of nasopharyngeal carcinoma (NPC). The DC-SIGN SNPs rs7252229, rs4804803, rs2287886, and rs735240 were genotyped in 477 unrelated NPC patients and 561 cancer-free controls. At rs7252229, risk of NPC was significantly lower in individuals with GC (odds ratio [OR] 0.076, 95% confidence interval [CI] 0.008-0.690), GG (OR 0.056, 95%CI 0.006-0.487), or GC + GG (OR 0.059, 95%CI 0.007-0.515) than in individuals with the CC genotype, after adjusting for age, gender, smoking history, and EBV-VCA-IgA status. At rs4804803, risk of NPC was significantly higher in individuals with the genotype GG than in those with the genotype AA (adjusted OR 9.038, 95%CI 1.708-47.822). At rs735240, risk of NPC did not change significantly with genotypes AG, GG, or AG + GG after adjusting for age, gender, and smoking history. However, when data were also adjusted for EBV-VCA-IgA status, three genotypes emerged as associated with significantly higher risk of NPC than the AA genotype: AG (OR 2.976, 95%CI 1.123-7.888), GG (OR 3.314, 95%CI 1.274-8.622), or GG + AG (OR 3.191, 95%CI 1.237-8.230). Our results suggest that DC-SIGN SNPs rs7252229, rs4804803, and rs735240 may influence NPC risk in the Chinese population. The mechanisms mediating this risk require a further study.

Small Numbers, Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand.

PURPOSE: This study was undertaken to determine cancer survival and describe the unique spectrum of cancers diagnosed among New Zealand's adolescents and young adult (AYA) population. METHODS: Registrations for 1606 15-24 year olds diagnosed with a new primary malignant tumor between 2000 and 2009 were obtained from the New Zealand Cancer Registry and classified according to AYA diagnostic group and subgroup, age, sex, and prioritized ethnicity. Age-standardized incidence rates (IRs) per million person years and 5-year relative survival ratios were calculated. RESULTS: Cancer incidence was 228.6 per million for adolescents aged 15-19 years and 325.7 per million for young adults aged 20-24 years. Overall IRs were consistent across all ethnic groups but there were unique ethnic differences by tumor group including a higher incidence of bone tumors, carcinoma of the gastrointestinal tract, and gonadal germ cell tumors among Maori, a higher incidence of leukemia among Pacific peoples, and a higher incidence of melanoma among non-Maori/non-Pacific peoples. Five-year relative survival for adolescents (75.1%) and AYA overall (80.6%) appeared poorer than had been achieved in other high-income countries. Maori (69.5%) and Pacific (71.3%) AYA had lower 5-year survival compared to non-Maori/non-Pacific peoples (84.2%). CONCLUSION: The survival disparities observed require further investigation to identify and address the causes of these inferior outcomes. The newly established AYA Cancer Network Aotearoa has been tasked with improving cancer survival and care and ensuring equality of access for New Zealand AYAs with cancer.

Association of genetic polymorphisms with laryngeal carcinoma prognosis in a Chinese population.

We analyzed the effects of single-nucleotide polymorphisms (SNPs) on laryngeal carcinoma (LC) risk and overall survival (OS) in 170 Chinese male LC patients followed for 10 years. After assessment of clinical characteristics (age, laryngectomy, neck dissection, tumor differentiation, TNM status), the patients were genotyped for 24 SNPs associated with risk in multiple cancers. LC risk was assessed using log-rank test and Cox proportional hazard models. The median OS time was 48 months. By the follow-up deadline, OS was 41.2%. Kaplan-Meier analysis indicated 1-, 3-, and 5-year survival rates to be 84.7%, 57.2%, and 47.1%, respectively. Five LC clinicopathological characteristics, namely total laryngectomy (TL), low differentiation (LD), T3-T4, N1-N2, and clinical stage III-IV were associated with worse OS (HR: 2.35, p < 0.001; HR: 2.39, p = 0.02; HR: 2.17, p < 0.001; HR: 2.39, p < 0.001; and HR: 3.29, p < 0.001, respectively). Univariate cox regression analysis indicated that four SNPs were associated (p < 0.05) with LC OS in the codominant genetic model compared to patients with the homozygous wild-type genotype: rs10088262 G/A (HR = 1.57), rs1665650 A/G (HR = 0.65); rs3802842 C/C (HR = 2.18), and rs59336 T/A and T/T (HR = 0.61 and 2.61, respectively).

Incidence of bladder cancer after radiation for prostate cancer as a function of time and radiation modality.

OBJECTIVES: To evaluate the risk of BlCa developing after radiation for PCa, stratified by ethnicity and follow-up duration. METHODS: The 1973-2011 surveillance, epidemiology and end results database was used to determine the observed and expected number of BlCa after PCa radiation. The adjusted relative risks (RRs) of developing BlCa were calculated for the various radiation modalities relative to no radiation, stratified by ethnicity and follow-up duration. BlCa characteristics were compared between patients with a history of prostate radiation and those without PCa. RESULTS: PCa was radiated in 346,429 men, 6401 of whom developed BlCa versus 2464 expected cases [SIR (95 % CI) of 2.60 (2.53-2.66)]. All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. Post-radiation BlCa, in particular that after brachytherapy, had higher grade (P = 0.0001) and lower stage (P = 0.0001) versus the general population. CONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. Bladder cancers after prostate radiation, especially after brachytherapy, are generally lower stage but higher grade than those in patients without PCa.

Racial and Ethnic Disparities in Nasopharyngeal Cancer Survival in the United States.

Objective To determine whether patient race and ethnicity affect nasopharyngeal cancer survival. Study Design Retrospective database analysis. Setting National Cancer Institute's SEER database (Surveillance, Epidemiology, and End Results), 1988-2010. Subjects and Methods Nasopharyngeal carcinoma cases were extracted according to site codes and histology recode-broad groupings. The cohort of 5427 patients was used to calculate disease-specific survival in regard to race and ethnicity. Extracted data were further analyzed through direct comparisons and multivariable Cox regression models controlling for patient, tumor, and treatment characteristics. Results Unadjusted survival curves for all nasopharyngeal carcinomas considered together showed a statistically significant better disease-specific survival for the African American race ( P = .02) and Asian ethnicity ( P = .01) relative to Caucasian patients. The survival advantage for both these groups was eliminated after controlling for the age and sex of the patients. Conclusion African American and Asian patients with nasopharyngeal cancer have better disease-specific survival as compared with Caucasian patients, while Hispanic ethnicity has no effect relative to Caucasians. This disparity is accounted for by diagnosis at an older age in Caucasian patients but remains poorly explained in regard to Hispanic patients.

Outcomes and Prognostic Factors of Primary Urethral Cancer.

OBJECTIVE: To identify prognostic and treatment factors for primary urethral cancer using a nationwide database. MATERIALS AND METHODS: The National Cancer Database was queried for all cases of primary urethral cancer from 2004 to 2013. Patients with other cancer diagnoses, metastasis, or diagnosis on autopsy were excluded. Proportional hazards regression was used to identify independent predictors of overall survival in patients with primary urethral cancer. Because we hypothesized that predictors may covary by sex, we also performed regression analysis stratified by sex. RESULTS: We identified 1268 men and 869 women with primary urethral cancer. Women tended to have more advanced tumors and adenocarcinoma histology. Median survival for the entire cohort was 49 months (43-55), with 5- and 10-year survival rates of 46% and 31%, respectively. On multivariate analysis, age, race, stage, grade, and Charlson comorbidity index were independent predictors of overall survival. Histology was not a predictor of overall survival in the combined model; however, adenocarcinoma in women increased hazards of death, whereas it decreased hazards of death in men when compared with squamous cell carcinoma. CONCLUSION: Men and women with primary urethral cancer had significant differences in histology, grade, and nodal status. In addition to several expected disease-related factors, black race was associated with increased mortality for patients with primary urethral cancer.

Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A migrant cohort study of 2.3 million Jewish Israeli adolescents.

Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16-19 between the years 1967 and 2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards were used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p = 4.72.10-6 and 3.86; 95% CI 1.77-8.41; p = 0.00067, respectively). These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of NPC.

Incidence and survival of sebaceous carcinoma in the United States.

BACKGROUND: Information on risk factors, epidemiology, and clinical characteristics of sebaceous carcinoma (SC) is limited. OBJECTIVE: We sought to analyze trends in SC in the United States from 2000 through 2012. METHODS: We used data from the 18 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from 2000 to 2012 to calculate the cause of death, relative frequencies/incidences, 5-/10-year Kaplan-Meier survival, hazard ratios, and incidence rates for SC. Each parameter was analyzed by age, location of occurrence (ocular/extraocular), race, sex, and SEER registry. RESULTS: Overall incidence was 0.32 (male) and 0.16 (female) per 100,000 person-years. Incidence significantly increased, primarily because of an increase among men. Incidence among whites was almost 3 times the rate among non-whites. Male sex (P < .0001), black race (P = .01), and extraocular anatomic location (P < .0001) were associated with significantly higher all-cause mortality. However, overall case-specific mortality for SC decreased significantly. LIMITATIONS: Underregistration of patients in SEER registries, lack of verification of individual diagnoses, and low levels of staging data because of low stage-classification rate are limitations. CONCLUSIONS: The overall incidence of SC is increasing significantly. Male sex, black race, and extraocular occurrences are associated with significantly greater mortality.

Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database.

The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases.

Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk.

Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent genome-wide association (GWA) and candidate studies identified 6 single nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267, rs944289, and rs116909374), associated with increased TC risk in Europeans but their effects on disease risk have not been comprehensively tested in Hispanics. In this study, we aimed to describe the main clinicopathological manifestations and to evaluate the effects of known SNPs on TC risk and on clinicopathological manifestations in a Hispanic population.We analyzed 281 nonmedullary TC cases and 1146 cancer-free controls recruited in a multicenter population-based study in Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain reaction (KASP) technique. Association between genetic variants and TC risk was assessed by computing odds ratios (OR) and confidence intervals (CIs).Consistent with published data in U.S. Hispanics, our cases had a high prevalence of large tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26), rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18). Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 × 10). Individuals with ≥6 risk alleles had >6-fold increased TC risk (OR = 6.33, P = 4.0 × 10) compared to individuals with ≤2 risk alleles. rs944289T and rs116909374A were strongly associated with follicular histology (ORs = 1.61 and 3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with regional disease (OR = 1.92).To our knowledge, this is the first study of known TC risk variants in South American Hispanics and suggests that they increase TC susceptibility in this population and can identify patients at higher risk of severe disease.