Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County,Guangdong Province,South China:an age-period-cohort analysis

Introduction:In the past several decades,declining incidences of nasopharyngeal carcinoma(NPC) have been observed in Chinese populations in Hong Kong,Taiwan,Los Angeles,and Singapore.A previous study indicated that the incidence of NPC in Sihui County,South China remained stable until 2002,but whether age,diagnosis period,and birth cohort affect the incidence of NPC remains unknown.Methods:Age-standardized rates(ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011.Joinpoint regression analysis was conducted to quantify the changes in incidence trends.A Poisson regression age-period-cohort model was used to assess the effects of age,diagnosis period,and birth cohort on the risk of NPC.Results:The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females.The incidence of NPC remained stable at a non-significant average annual percent change of 0.2%for males and-1.6%for females throughout the entire period.A significantly increased estimated annual percent change of 6.8%(95%confidence interval,0.1%-14.0%) was observed from 2003 to 2009 for males.The relative risk of NPC increased with advancing age up to 50-59 and decreased at ages >60 years.The period effect curves on NPC were nearly flat for males and females.The birth cohort effect curve for males showed an increase from the1922 cohort to the 1957 cohort and a decrease thereafter.In females,there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort.Conclusions:The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011,with an increase from 2003 to 2009.The relative risks of NPC increased in younger females.

Secular trend analysis of lung cancer incidence in Sihui city,China between 1987 and 2011

Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear.The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.Methods:Joinpoint regression analysis and the age-period-cohort(APC) model were used to analyze the lung cancer incidence trends in Sihui,Guangdong province,China between 1987 and 2011,and explore the possible causes of these trends.Results:A total of 2,397 lung cancer patients were involved in this study.A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period.Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period,a sharp acceleration was observed in males starting in 2005.The full APC model was selected to describe age,period,and birth cohort effects on lung cancer incidence trends in Sihui.The age cohorts in both sexes showed a continuously significant increase in the relative risk(RR)of lung cancer,with a peak in the eldest age group(80-84 years).The RR of lung cancer showed a fluctuating curve in both sexes.The birth cohorts identified an increased trend in both males and females;however,males had a plateau in the youngest cohorts who were born during 1955-1969.Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts.Social aging,smoking,and environmental changes may play important roles in such trends.

Familial nasopharyngeal carcinomas possess distinguished clinical characteristics in southern China

Objective： To compare clinical characteristics between familial nasopharyngeal carcinomas（NPCs） and sporadic NPCs in Guangdong province, China, a high-risk area.Methods： Between 1991 and 2001, 993 NPC patients treated at the Cancer Center of Sun Yat-Sen University in Guangdong were randomly selected as probands. Information about NPC among the probands＇ relatives and other information were obtained from a retrospective review of the patients＇ medical records. The patients were divided into sporadic NPC, low-frequency familial NPC（one NPC patient in addition to the proband in three generations）, and high-frequency familial NPC（2 or more additional NPC patients in three generations） groups. Pathological and clinical characteristics were compared among these groups.Results： Of the 993 patients, 131（13.2%） had a familial history of NPC. The average age at diagnosis was the lowest in the high-frequency familial NPC group（39 years; P=0.048）. Although the overall survival（OS）, distant metastasis-free survival（DMFS）, and disease-free survival（DFS） rates did not differ between familial and sporadic NPCs, the locoregional recurrence-free survival（LRFS） rate increased in the order sporadic NPCs, low-frequency familial NPCs, and high-frequency familial NPCs（P=0.009）, with 5-year rates of 70%, 83%, and 87%, respectively. Multivariate analysis showed that family history of NPC was an independent favorable prognostic factor for LRFS, with adjusted hazard ratio（a HR） of 0.548, 95% CI（0.342-0.878）. The high LRFS for familial NPCs was mainly noted among young, advanced-stage patients who received continuous radiation treatment.Conclusions： Genetic factors may play an important role in the etiology of high-frequency familial NPC and underlie the early age of onset and sensitivity to radiotherapy.

Detection of nasopharyngeal carcinoma using surface-enhanced laser desorption and ionization mass spectrometry profiles of the serum proteome

Background and Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC. Methods: A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later. Results: Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples. Conclusion: SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

Estimation of cancer burden in Guangdong Province,China in 2009

Background:Surveying regional cancer incidence and mortality provides significant data that can assist in making health policy for local areas;however,the province- and region-based cancer burden in China is seldom reported.In this study,we estimated cancer incidence and mortality in Guangdong Province,China and presented basic information for making policies related to health resource allocation and disease control.Methods:A log-linear model was used to calculate the sex-,age-,and registry-specific ratios of incidence to mortality(l/M) based on cancer registry data from Guangzhou,Zhongshan,and Sihui between 2004 and 2008.The cancer incidences in 2009 were then estimated according to representative l/M ratios and the mortality records from eight death surveillance sites in Guangdong Province.The cancer incidences in each city were estimated by the corresponding sex- and age-specific incidences from cancer registries or death surveillance sites in each area.Finally,the total and region-based cancer incidences and mortalities for the entire population of Guangdong Province were summarized.Results:The estimated l/M ratios in Guangzhou(3.658),Zhongshan(2.153),and Sihui(1.527) were significantly different(P < 0.001),with an average l/M ratio of 2.446.Significant differences in the estimated l/M ratios were observed between distinct age groups and the three cancer registries.The estimated l/M ratio in females was significantly higher than that in males(2.864 vs.2.027,P < 0.001).It was estimated that there were 163,376 new cancer cases(99,689 males and 63,687 females) in 2009;it was further estimated that 115,049 people(75,054 males and 39,995females) died from cancer in Guangdong Province in 2009.The estimated crude and age-standardized rate of incidences(ASRI) in Guangdong Province were 231.34 and 246.87 per 100,000 males,respectively,and 156.98 and 163.57 per 100,000 females,respectively.The estimated crude and age-standardized rate of mortalities(ASRM) in Guangdong Province were 174.17 and 187.46 per 100,000 males,respectively,and 98.59 and 102.00 per 100,000 females,respectively.In comparison with the western area and the northern mountain area,higher ASRI and ASRM were recorded in the Pearl River Delta area and the eastern area in both males and females.Conclusions:Cancer imposes a heavy disease burden,and cancer patterns are unevenly distributed throughout Guangdong Province.More health resources should be allocated to cancer control,especially in the western and northern mountain areas.

Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China:a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.

Current cancer situation in China:good or bad news from the 2018 Global Cancer Statistics?

Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should include effective tobacco-control policy,recommendations for healthier lifestyles,along with enlarg-ing the coverage of effective screening,educating,and vaccination programs to better sensitize greater awareness control to the general public.

Decreased macrophage inflammatory protein (MIP)-1α and MIP-1β increase the risk of developing nasopharyngeal carcinoma

Background:The association of circulating inflammation markers with nasopharyngeal carcinoma(NPC)is still largely unclear.This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.Methods:The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study(150 NPC patients and 150 controls)using multiplex assay platforms.Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection.Odds ratios(ORs)and 95%confidence intervals(CIs)relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models.The associations were validated in 60 patients with NPC and 120 con-trols in a subsequent nested case-control study within a NPC screening trial.Potential interactions between serum cytokines and Epstein-Barr virus(EBV)relating to the risk of NPC were assessed using a likelihood ratio test.Results:The levels of serum macrophage inflammatory protein(MIP)-1αand MIP-1βin the highest categories were associated with a decreased risk of NPC in both the case-control study(MIP-1α:OR=0.49,95%CI=0.26-0.95;MIP-1β:OR=0.47,95%CI=0.22-1.00)and the nested case-control study(MIP-1α:OR=0.13,95%CI=0.03-0.62;MIP-1β:OR=0.20,95%CI=0.04-0.94),compared with those in the lowest categories.Furthermore,individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study(MIP-1α:OR=16.28,95%CI=7.11-37.23;MIP-1β:OR=12.86,95%CI=5.9-28.05)and the nested case-control study(MIP-1α:OR=86.12,95%CI=10.58-701.03;MIP-1β:OR=115.44,95%CI=13.92-957.73).Conclusions:Decreased preclinical MIP-1αand MIP-1βlevels might be associated with a subsequently increased risk of NPC.More mechanistic studies are required to fully understand this finding.

Transcriptome-wide association analysis identified candidate susceptibility genes for nasopharyngeal carcinoma

Dear Editor,Nasopharyngeal carcinoma(NPC)is a common malignancy in East and Southeast Asia,especially in South China.The etiology of NPC has been linked to genetic susceptibility,Epstein-Barr virus(EBV)infection,and environmental factors.Accumulated evidence including multiple genome-wide association studies(GWASs)has revealed robust genetic predisposition of NPC.However,GWAS-identified genetic variants collectively account for only 8.2%of NPC heritability[1].The underlying inherited predisposition is largely undetermined.The strongest genetic signal for NPC consistently hits the human leukocyte antigen(HLA)region on 6p21[2].However,the highly polymorphic nature and complicated long-range linkage disequilibrium(LD)in the HLA region particularly obscure the causal variants driving the association.In addition,most genetic variants located in introns or intergenic regions.The causal genes mediating genetic effects on NPC risk have rarely been ascertained by GWAS alone.