AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions.
METHODS: This study was designed as a population-based screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse.
RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively.
CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions.
DNA image cytometry; Aneuploidy; Screening; Esophageal cancer; Precancerous lesions
AIM: To estimate the cost-benefit of endoscopic screening strategies of esophageal cancer (EC) in high-risk areas of China.
METHODS: Markov model-based analyses were conducted to compare the net present values (NPVs) and the benefit-cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied according to the targeted screening age, screening frequencies, and follow-up intervals. Model parameters were collected from population-based studies in China, published literatures, and surveillance data.
RESULTS: Compared with non-screening outcomes, all strategies with hypothetical 100 000 subjects saved life years. Among five dominant strategies determined by the incremental cost-effectiveness analysis, screening once at age 50 years incurred the lowest NPV (international dollar-I$55 million) and BCR (2.52). Screening six times between 40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy, screening thrice between 40-70 years at a 10-year interval resulted in relatively lower NPV, but the same BCR.
CONCLUSION: EC endoscopic screening is cost-beneficial in high-risk areas of China. Policy-makers should consider the cost-benefit, population acceptance, and local economic status when choosing suitable screening strategies.
Cost-benefit analysis; Esophageal cancer; Endoscopy; Screening; High-risk area
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
AIM: To clarify the similarities and differences in gastric cancer epidemiology between Japan and China.
METHODS: A comprehensive literature search of the PubMed database was performed. The relevant literature published in China was also been cited. Data on incidence and mortality rates in 2008 were obtained from the Cancer Mondial database, published by International Agency for Research on Cancer at http://www-dep.iarc.fr/.
RESULTS: Gastric cancer remains a significant public health burden in both Japan and China. The prevalence of Helicobacter pylori (H. pylori) colonization is high in the adult populations of both countries. Accumulating evidence from intervention studies in both countries has shown the effectiveness of H. pylori eradication in reducing gastric cancer incidence. There are differences, however, in many aspects of gastric cancer, including patterns of incidence and mortality, trends in the prevalence of H. pylori infection, H. pylori strains, the magnitude of risk of gastric cancer related to H. pylori infection, and associations with dietary habits. Compared with China, Japan has seen a more rapid decline in H. pylori infection among adolescents. While Japanese cohort studies have dominated the literature concerning the associations between gastric cancer and dietary habits, numerous case-control studies in China suggest a positive association between a high intake of preserved fish and vegetables and gastric cancer risk. There is a need for a multidisciplinary research approach to understand the interactions between various strains of H. pylori, host factors, and other lifestyle and environmental factors in gastric carcinogenesis in both countries.
CONCLUSION: The shared high incidence of gastric cancer and high prevalence of H. pylori, as well as differences in many aspects of gastric cancer, provide an excellent opportunity to establish Sino-Japanese collaborations.
Gastric cancer; Risk factor; Helicobacter pylori; Epidemiology
Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy, but little is known about the presence or characteristics of MCC in mainland China. A retrospective chart review was conducted to describe the clinical profile of Merkel cell carcinoma in China.
At 18 cancer or dermatology hospitals in metropolitan centers from the six geographical regions of mainland China, approximately 3,100,000 pathology database and medical records were searched for cases that had a pathological diagnosis of MCC between 1970 and 2009. A case series was compiled from retrospective chart reviews of identified MCC patients.
Eight out of 18 participating hospitals reported at least one record of a patient with a pathological diagnosis of MCC, and a total of 22 cases were identified. The median age of patients was 65.5, and 59% were female. The median time from the appearance of a lesion to the time of biopsy was 6 months, and the most common location of lesions was the head and neck. The most common treatment used was surgery alone.
MCC appears to be uncommon in mainland China. Patients in this series are elderly, often had lesions on the head/neck region, and most commonly received surgery alone as treatment. In contrast with MCC in Western countries, the current series' patients were all of Asian ethnicity, had larger lesions at presentation, and none were documented as having HIV or other forms of immunosuppression.
Merkel cell carcinoma; China; skin cancer; case-series
Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations.
To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref‐1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China.
The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real‐time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age‐ and a sex‐stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs.
No association was observed between polymorphisms in APE/ref‐1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010).
Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke.
Linzhou, China has one of the highest rates of esophageal squamous cell carcinoma in the world. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), may play a role in this increased risk. To better understand PAH sources, we measured PAHs in the air and food of 20 non-smokers over multiple days and compared the concentrations to a urinary PAH biomarker, 1-hydroxypyrene glucuronide (1-OHPG). Sampling occurred over four consecutive days. Kitchen air samples (days 2–3) and duplicate diet samples (days 1–4) were analyzed for 14 or more unique PAHs, including BaP. Daily urine samples (days 1–3) were analyzed for 1-OHPG. Mixed-effects models were used to evaluate the associations between air or food PAH concentrations and urine 1-OHPG concentrations. The median kitchen air BaP concentration was 10.2 ng/m3 (inter-quartile range (IQR): 5.1–20.2 ng/m3). The median daily food BaP concentration and intake were 0.08 ng/g (IQR=0.04–0.16 ng/g) and 86 ng/day (IQR=41–142 ng/day), respectively. The median 1-OHPG concentration was 3.36 pmol/mL (IQR=2.09–6.98 pmol/mL). In mixed-effects models, 1-OHPG concentration increased with same-day concentration of food BaP (p=0.07). Though PAH concentrations in air were not associated with 1-OHPG concentrations, the high concentrations of PAHs in both air and food suggest that they are both important routes of exposure to PAHs in this population. Further evaluation of the role of PAH exposure from air and food in the elevated rates of esophageal cancer in this region is warranted.
polycyclic aromatic hydrocarbons; cancer; China; dietary exposure; inhalation exposure; biomonitoring; multimedia exposure assessment
Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC.
fumonisin; hepatocellular carcinoma; cohort study; China; epidemiology
This study aims to analyze the clinical-pathological characteristics of multifocal and multicentric breast cancer (MMBC) in Chinese women.
Sixty-seven cases with MMBC were randomly collected and reviewed at seven hospitals in representative districts of China during 1999 to 2008.
The incidence of MMBC in breast cancer in China was 1.75%. Compared to those with unifocal breast cancer, women with MMBC were more likely to have larger tumor size, lymph node metastasis (59.70% vs. 45.62%) and stage III to IV (46.26% vs. 21.10%). The peak age at onset of MMBC was 40 to 49 years old and has been gradually increasing during 1999 to 2008. Most of the MMBC women were treated with surgery and adjuvant therapy.
In China, the incidence of MMBC in breast cancer is significantly lower than that in Western countries. Compared to unifocal breast cancer, MMBC is biologically more aggressive. Most MMBC women underwent mastectomy, instead of breast conservation surgery.
Breast; Carcinoma; Clinical pathology
Iodine concentrates in gastric tissue and may act as an antioxidant for the stomach. We previously showed that self-reported goiter was associated with significantly increased risk of gastric noncardia adenocarcinoma (GNCA) and non-significantly increased risks of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) in a prospective case-cohort study in a high-risk population in China. Negatively correlated with iodine levels, serum thyroglobulin (Tg) is a more sensitive biomarker of iodine deficiency than goiter. This study aimed to determine whether baseline serum Tg was also associated with development of GNCA, GCA, and ESCC in the same cohort, the Linxian General Population Nutrition Intervention Trial. Sera from approximately 200 subjects of each case type and 400 non-cases were tested for serum Tg concentration using appropriate assays. Tg was modeled as sex- and assay-specific quartiles in Cox regression models adjusted for age, smoking, alcohol, Helicobacter pylori status, pepsinogens I/II ratio, family history, and commune of residence. In the final combined analysis, participants in the highest quartile of serum Tg, compared to those in the lowest quartile, had adjusted Hazard Ratios of 0.88 (95% confidence interval 0.50–1.52), 1.14 (0.63–2.05), and 0.78 (0.47–1.31) for GNCA, GCA, and ESCC, respectively. Using serum Tg, a sensitive biomarker of iodine deficiency, we found no association between serum Tg concentrations and risk of these upper gastrointestinal (UGI) cancers in the study population. Our results do not support the hypothesis that iodine deficiency, as assessed by serum Tg, is associated with an increased risk of UGI cancers.
iodine deficiency; esophageal cancer; gastric cancer; thyroglobulin; China
Cancers of the upper gastrointestinal tract remain a significant cause of morbidity and mortality. Cysteine, known to be involved in a myriad of immuno-modulatory, anti-oxidant, and anti-carcinogenic pathways, has not been investigated in the aetiology of oesophageal or gastric cancers. To examine the relationship between serum cysteine concentration and risk of these cancers we conducted a nested case-cohort study within the General Population Nutrition Intervention Trial in Linxian, China.
498 oesophageal squamous cell carcinomas (OSCC) and 255 gastric cardia adenocarcinomas (GCA) were matched by age and sex to 947 individuals from the wider cohort. We calculated hazard ratios (HR) and 95% confidence intervals (95% CI) using the case-cohort estimator for the Cox proportional hazards models, stratified on age and sex, with adjustment for potential confounders.
Higher concentrations of serum cysteine were significantly associated with a lower risk of both OSCC and GCA. For those in the highest quartile of serum cysteine, compared to those in the lowest, the multivariate HRs were 0.70 for OSCC (95% CI: 0.51, 0.98) and 0.59 for GCA (95% CI: 0.38, 0.91). These associations were dose dependent (P for trend = 0.006 and 0.008, respectively). These inverse associations were not significantly modified by other risk factors, with the exception of age, where a stronger association was noted among persons in the older age strata.
Higher serum concentrations of cysteine were associated with a significantly reduced risk of OSCC and GCA. Cysteine should be further investigated for its potential as a chemopreventive agent for upper gastrointestinal cancers.
oesophageal squamous cell carcinoma; gastric cardia cancer; hazard ratio; cysteine
Background and Objectives
Linxian in Henan Province, China, has among the highest rates of esophageal cancer worldwide. Little is known about long-term survival after esophagectomy for early neoplastic lesions found during early detection screening. A long-term survival analysis was performed for 315 patients from Linxian who received esophagectomy for early esophageal squamous cell carcinoma.
Cases that received esophagectomy for early esophageal squamous cell carcinoma were age- and gender-matched with two healthy controls, and Kaplan-Meier survival analyses were performed for both groups.
10-year survival was 77% for cases and 64% for controls, and this difference was not statistically significant (p = 0.33). There were no significant differences in survival based on age or gender (p>0.05). Cases with esophageal squamous cell carcinoma-in-situ had significantly better survival than cases with invasive esophageal squamous cell carcinoma (p=0.035).
Survival of cases who received esophagectomy for early esophageal squamous cell carcinoma was not significantly different from survival of age- and gender-matched controls. Early intervention probably improved survival rates for these patients who otherwise would most likely have developed advanced esophageal carcinoma. Early screening and intervention are highly relevant in areas with a high risk of esophageal cancer such as Linxian, China.
Esophageal Cancer; Esophageal Surgery; Statistics; survival analysis
To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors (RFs, including nulliparity, mean number of children, age at first birth and breastfeeding), use of oral contraceptives (OCs, restricted to the age group of 15-49 years), and hormone replacement therapy (HRT), as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005.
We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure.
Exposure of RFs in 2001 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer (711 cases, 294 deaths). The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction (PAF) of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths.
RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.
Reproductive factors; Oral contraceptives; Hormone replacement therapy; Cancer; Population attributable fraction
Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.
We compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.
Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing.
The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.
To provide an evidence-based and consistent assessment of the burden of cancer attributable to inadequate fruit and vegetable intake in China in 2005.
The proportions of cancers attributable to low consumption of vegetable and fruit were calculated separately to estimate the burden of related cancers for the year 2005 in China. Data on the prevalence of exposure were derived from a Chinese nutrition and health survey. Data on relative risks were mainly derived from meta-analysis. Attributable fractions were calculated based on the counterfactual scenario which was a shift in the exposure distribution.
The total cancer burden attributable to inadequate consumption of fruit was up to 233,000 deaths (13.0% of all cancers) and 300,000 cases (11.6% of all cancers) in 2005. Increasing consumption of vegetable to the highest quintile could avoid total cancer deaths and cases by 3.6% (64,000 persons) and 3.4% (88,000 persons). The contributions to cancer burden were higher in rural areas than in urban areas. They have greater influence on men than on women. The largest proportions of cancer burden attributable to low fruit and vegetable intake were for oral and pharyngeal cancers.
This study showed that inadequate intake of fruit and vegetable makes a significant contribution to the cancer burden. Increasing consumption of fruit and vegetable could prevent many cancer deaths and save many lives. Promoting the consumption of fruit and vegetable is an important component in diet-based strategies for preventing cancer.
Fruit; Vegetable; Cancer; Population attributable fraction; China
This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine down-regulated IL-2 by 9% (p=0.04), while celecoxib down-regulated IL-7 by 11% (p=0.006) and up-regulated IL-13 by 17% (p=0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall (OR=1.47, p=0.03) and among those with mild dysplasia at t0 (OR=2.53 p=0.001). An increase in IL-2 tertile from baseline to t10 was also non-significantly associated with worsening dysplasia for all participants (OR=1.32 p=0.098), and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR=2.0 p=0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR=2.52 p=0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, while celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10 month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect on reducing levels of IL-2.
chemoprevention; interleukin-2; preneoplasia; gastrointestinal tract; selenium
More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the country's second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country.
The global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005) to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure.
At the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central). The anticipated study population from the China national study is approximately 9000 patients.
Findings from the HCC BRIDGE China national study, the first geographically representative study of hepatocellular carcinoma in China, will contribute to the understanding of patterns of therapy use and related clinical outcomes and will provide further information on continuing unmet needs for hepatocellular carcinoma throughout this important country.
This paper aims to provide evidence-based recommendations for health professionals, to develop a comprehensive cervical cancer program for a clinic, a community, or a country. Ensuring access to healthcare is the responsibility of all societies, and the Asia Oceania Research Organisation in Genital Infections and Neoplasia (AOGIN) is committed to working collaboratively with governments and health professionals to facilitate prevention programs, to protect girls and women from cervical cancer, a disease that globally affects 500,000 and kills nearly 300,000 women annually, just over half of whom are in the Asia Oceania region. We share the vision that a comprehensive program of vaccination, screening, and treatment should be made accessible to all girls and women in the world.
The primary purpose of these guidelines is to provide information on scientific evidence on the different modalities and approaches of cervical cancer prevention programs, for high resource and low resource settings. The secondary purpose is to provide an overview of the current situation of cervical cancer control and prevention in various Asian Oceania countries: their views of an ideal program, identified obstacles, and suggestions to overcome them are discussed.
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×10−9; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old. This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia (CIN) in women aged 18-25, as well as their knowledge of and attitudes towards HPV vaccination.
A population-based cervical cancer screening study was conducted on women aged 18-25 in Jiangsu province in 2008. Participants provided socio-demographic, reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination. Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology (LBC) as well as visual inspection with acetic acid (VIA). Women testing positive for any test were referred to colposcopy and biopsy. The gold standard for diagnosis of cervical lesions was directed or random biopsies.
Within the sample of 316 women, 3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA. Among these young women, extra-marital sexual behavior of them (OR=2.0, 95%CI: 1.1-3.8) or their husbands (OR=2.6, 95%: 1.4-4.7) were associated with an increased risk of HPV positivity. Although overall HPV awareness was low, after a brief educational intervention, 98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated. However, most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50-100 RMB, respectively.
Our study indicates cervical disease burden is relatively high among sampled Chinese women aged 18-25. Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.
Cervical cancer; Cervical intraepithelial neoplasia; Human papillomavirus; Knowledge; Attitude
Polycyclic aromatic hydrocarbon (PAH) exposure is a risk factor for esophageal squamous cell carcinoma (ESCC), and PAHs are ligands of the aryl hydrocarbon receptor (AhR). This study measured the expression of AhR and related genes in frozen esophageal cell samples from patients exposed to different levels of indoor air pollution, who did or did not have high-grade squamous dysplasia (HGD), and who did or did not have a family history (FH) of upper gastrointestinal cancer (UGI Ca).
147 samples were evaluated, including 23 (16%) from patients with HGD and 48 (33%) from patients without DYS who heated their homes with coal, without a chimney (a “high” indoor air pollution group), and 27 (18%) from patients with HGD and 49 (33%) from patients without DYS who did not heat their homes at all (a “low” indoor air pollution group). Nearly half (64 (44%)) had a FH of UGI Ca. RNA was extracted and Quantitative-PCR analysis was performed.
AhR gene expression was detectable in 85 (58%) of the samples, and was more than 9-fold higher in those with a FH of UGI Ca (median expression (IQR) -1964 (-18000, -610) versus -18000 (-18000, -1036) Wilcoxon P = 0.02). Heating status, dysplasia category, age, gender, and smoking were not associated with AhR expression (linear regression, all P-values ≥0.1).
AhR expression was higher in patients with a FH of UGI Ca. Such individuals may be more susceptible to the deleterious effects of PAH exposure, including PAH-induced cancer.
Gastrointestinal tract cancer; Esophagus; Aryl hydrocarbon receptor; family history of cancer; gene expression; polycyclic aromatic hydrocarbons
Low serum pepsinogen I (PGI) and low pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy. We aimed to prospectively test the association between serum PGI/II ratio and risks of gastric noncardia adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma.
Case-cohort study nested in a prospective cohort with over 15 years of follow-up.
Rural region of the People’s Republic of China.
Men and women aged 40-69 at study baseline.
Main outcome measures
Adjusted hazard ratios and 95% confidence intervals for the association between serum PGI/II ratio and caner risk
Compared to subjects with PGI/II ratio of > 4, those with ≤4 had HRs (95%CIs) of 2.72 (1.77-4.20) and 2.12 (1.42-3.16) for noncardia and cardia gastric cancers, respectively. Risk of both cancers were also increased when other cut points ranging from 3 to 6, or when we used quartile models, or nonlinear continuous models. Risk of ESCC was marginally increased in those with PGI/II ratio ≤4, with HR (95% CI) of 1.56 (0.99-2.47), but quartile models and continuous models showed no increased risk. The nonlinear continuous models suggested that any single cut point collapsed subjects with dissimilar gastric cancer risks, and that using cut points was not an efficient use of data in evaluating these associations.
In this prospective study, we found similar and significantly increased risks of noncardia and cardia gastric adenocarcinomas in subjects with low PGI/II ratio, but little evidence for an association with ESCC risk.
Gastric cancer; Esophageal cancer; Pepsinogen; Case-cohort
The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29 584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with “factor D,” a combination of 50 μg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.
Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.
Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .47). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.
The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.
Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma (ESCC), and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures of vitamin D exposure have reached different conclusions about the association between vitamin D and risk of developing esophageal cancer.
We measured serum 25-hydroxyvitamin D (25(OH)D) concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing ESCC. All subjects underwent endoscopy and biopsy and were categorized by presence or absence of histologic squamous dysplasia. We used crude and multivariate adjusted generalized linear models to estimate the relative risk (RR) and 95% confidence intervals (CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration.
Two hundred and thirty (32%) of 720 subjects had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations then subjects without dysplasia, 36.5 and 31.5 nmol/L respectively (Wilcoxon two-sample test p = 0.0004). In multivariate adjusted models, subjects in the highest compared to the lowest quartile were at significantly increased risk of squamous dysplasia, RR (95% CI) = 1.86 (1.35–2.62). Increased risks were similar when examined in men and women separately: Men RR (95% CI) = 1.74 (1.08–2.93); Women RR (95% CI) = 1.96 (1.28–3.18).
Higher serum 25(OH)D concentration was associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding.
Esophageal cancer; Squamous dysplasia; Vitamin D; Serum 25(OH)D; China
Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I / pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC.
We measured serum PGI and PGII, using enzyme-linked immunosorbent (ELISA) assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking, and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).
Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles), or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08 − 4.18), comparing the lowest versus the highest quartile. The association between lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03.
Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC.
Esophageal cancer; Squamous dysplasia; Pepsinogen; China