Chuanhai Guo

Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations

Esophageal squamous-cell carcinoma (ESCC) is one of the most prevalent cancers worldwide and occurs at a relatively high frequency in China. To identify genetic susceptibility loci for ESCC, we conducted a genome-wide association study on 2,031 individuals with ESCC (cases) and 2,044 controls of Chinese descent using 666,141 autosomal SNPs. We evaluated promising associations in an additional 6,276 cases and 6,165 controls of Chinese descent from different areas of China. We identified seven susceptibility loci on chromosomes 5q11, 6p21, 10q23, 12q24 and 21q22 (ranging from P = 7.48 × 10−12 to P = 2.44 × 10−31); among these loci, 5q11, 6p21 and 21q22 were newly identified. Three variants in high linkage disequilibrium on 12q24 confer their risks to ESCC in a gene-lifestyle interaction manner, with more pronounced risk enhancement seen in tobacco and alcohol users. Furthermore, the identified variants had a cumulative association with ESCC risk (Ptrend = 7.92 × 10−56). These findings highlight the involvement of multiple genetic loci and gene-environment interaction in the development of esophageal cancer.

Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions

We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified six new ESCC susceptibility loci, of which four, at chromosomes 4q23, 16q12.1, 22q12 and 3q27 had a significant marginal effect (P = 1.78 × 10−39 to P = 2.49 × 10−11) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction P (PG × E) = 4.39 × 10−11 and PG × E = 4.80 × 10−8, respectively). Variants at the 4q23 locus, which includes the ADH cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (PG × E = 2.54 × 10−7 to PG × E = 3.23 × 10−2). We confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.

Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey

Background:The etiology of esophageal squamous cell cancer (ESCC) in high prevalence regions of China remains unclear.Methods:Endoscopic biopsies were conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China.Results:In this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma in situ and invasive ESCC. Using deep well (depth >100 meters) as water source (odds ratio=0.72, 95% confidence interval: 0.54–0.96) was negatively associated with ESCC and its precursors, whereas tobacco and alcohol use were not significantly associated with ESCC.Conclusions:Water source and other factors in this region need further evaluation by longitudinal studies.

The Anyang Esophageal Cancer Cohort Study: Study Design, Implementation of Fieldwork, and Use of Computer-Aided Survey System

Background Human papillomavirus (HPV) has been observed repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, the causal relationship between HPV infection and the onset of ESCC remains unknown. A large cohort study focusing on this topic is being carried out in rural Anyang, China. Methodology/Principal Findings The Anyang Esophageal Cancer Cohort Study (AECCS) is a population-based prospective endoscopic cohort study designed to investigate the association of HPV infection and ESCC. This paper provides information regarding the design and implementation of this study. In particular we describe the recruitment strategies and quality control procedures which have been put into place, and the custom designed computer-aided survey system (CASS) used for this project. This system integrates barcode technology and unique identification numbers, and has been developed to facilitate real-time data management throughout the workflow using a wireless local area network. A total of 8,112 (75.3%) of invited subjects participated in the baseline endoscopic examination; of those invited two years later to take part in the first cycle of follow-up, 91.9% have complied. Conclusions/Significance The AECCS study has high potential for evaluating the causal relationship between HPV infection and the occurrence of ESCC. The experience in setting up the AECCS may be beneficial for others planning to initiate similar epidemiological studies in developing countries.

Oral Human Papillomavirus Infection and Its Risk Factors among 5,410 Healthy Adults in China, 2009–2011

Background: Despite the established link between oral human papillomavirus (HPV) infection and a subset of oropharyngeal squamous cell carcinoma (OSCC), little is known about the epidemiology of oral HPV infection among healthy adults in China. Methods: Oral swab specimens and questionnaires were collected from 5,410 individuals (ages 25–65 years). HPV DNA in oral exfoliated cells was tested by general primer-mediated (SPF1/GP6+) PCR and sequencing. Univariate and multivariate analyses were performed to assess the associations between exposure factors and oral infection. Results: Alpha mucosal HPV types were detected in 0.67% [95% confidence interval (CI), 0.47%–0.93%] of 5,351 β-globin–positive specimens, and cutaneous HPV in 5.46% (95% CI, 4.86%–6.10%). HPV 16 and 3 were the most prevalent types of α mucosal (0.43%; 95% CI, 0.27%–0.64%) and cutaneous HPV (4.17%; 95% CI, 3.65%–4.74%), respectively. The prevalence of α mucosal HPV decreased with increasing age (25–65 years) from 0.93% to 0.36% (Ptrend = 0.033), and was associated with self-reported history of oral disease [adjusted odds ratio (OR), 4.78; 95% CI, 1.07–21.41]. In 1,614 heterosexual couples, cutaneous HPV in one partner was found to increase the other partners risk of cutaneous HPV infection (adjusted OR, 2.33; 95% CI, 1.22–4.48). Conclusions: Oral HPV infection, particularly with α mucosal types, is rare among healthy adults in China. A younger age and a history of oral disease imply higher risk of α mucosal HPV infection. Impact: This study addresses the paucity of epidemiological data on oral HPV infection among healthy population in China. Cancer Epidemiol Biomarkers Prev; 23(10); 2101–10. ©2014 AACR.

Seroprevalence of Merkel cell polyomavirus in the general rural population of Anyang, China.

Background Despite the probably causal link between Merkel cell polyomavirus (MCPyV) infection and Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy, little is known about the seroepidemiology of MCPyV among healthy adults in China. Methods Serum antibodies against MCPyV were evaluated by multiplex serology in a population-based study of 5548 adults (including 1587 heterosexual couples) aged 25–65 years who were enrolled from rural Anyang, China in 2007–2009. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for the seropositivity of MCPyV. Results The seroprevalence for MCPyV was 61.0%. MCPyV seropositivity was significantly higher in males than in females (64.5% vs. 57.7%, P<0.001), and for both genders, showed a trend of increase with age (Male: P trend<0.001; Female: P trend<0.001). Furthermore, among antibody positives, antibody levels of MCPyV increased with advancing age (P trend = 0.017). MCPyV seropositivity of one spouse was significantly associated with that of the other partner (Adjusted OR = 1.32, 95% CI: 1.07–1.62). However, there was no association between sexual behaviors and the seropositivity of MCPyV. Conclusions High seroprevalence of MCPyV was observed in healthy Chinese individuals. Serological evidence suggests that nonsexual horizontal spread of MCPyV can occur among family members, and further research in this regard is needed.

Anti-HPV-E7 seropositivity and risk of esophageal squamous cell carcinoma in a high-risk population in China

Results of previous serologic studies on the association of human papillomavirus (HPV) with esophageal squamous cell carcinoma (ESCC) have been inconsistent. From 2007 to 2010, the authors collected blood samples and relevant demographic data from 1435 patients with ESCC and 2071 age- and sex-matched normal controls from Anyang, China. HPV-16, 18 and 57 E7 antibodies were evaluated with the glutathione-S-transferase capture ELISA. The proportions of subjects who were positive for antibodies against these three HPV antigens in the case group were all significantly higher than those in the control group. In multivariate analysis, the presence of HPV-16 E7 antibody was associated with an increased risk of ESCC [odds ratio (OR) = 3.6, 95% confidence interval (CI): 2.5-5.0], whereas the presence of HPV-18 (OR = 1.1, 95% CI: 0.7-1.7) and HPV-57 (OR = 1.3, 95% CI: 0.9-1.9) antibodies were not significant after adjustment for HPV-16. In multiple cutoff value analysis, the lowest OR for HPV-16 was obtained with the standard cut point mean + 3 SD. This study provides serological evidence in support of HPV-16 infection playing a role in the occurrence of ESCC in a high-incidence area of China.

Prevalence, Incidence, Clearance, and Associated Factors of Genital Human Papillomavirus Infection among Men: A Population-Based Cohort Study in Rural China

Background: The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men. Methods: A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009–2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4–37.9 months). Results: The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51–65 years). Conclusions and Impact: This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population. Cancer Epidemiol Biomarkers Prev; 23(12); 2857–65. ©2014 AACR.

Seroprevalence of 10 human papillomavirus types in the general rural population of Anyang, China: a cross-sectional study

Objectives Data on the seroprevalence of human papillomavirus (HPV) in China are limited. The objective of this study was to characterise the serological profiles of HPV infection in a rural Chinese population and help establish effective vaccine policy. Methods Serum antibodies against the major capsid protein L1 of 10 HPV types (HPV-3, 6, 11, 16, 18, 45, 52, 57, 58 and 75) were evaluated with Luminex-based multiplex serology in a population-based study of 5548 adults (including 1587 couples) aged 25–65 years enrolled from rural Anyang, China, in 2007–2009. Results The seroprevalence for any HPV type and any of the types HPV-6/11/16/18 was 64.8% and 34.4%, respectively. 30.3% of adults were seropositive for any mucosal high-risk (HR) HPV, and HPV-58 (10.6%), HPV-16 (9.7%) and HPV-18 (9.3%) were the three most common types. 24.8% of seropositive individuals were positive for multiple mucosal HR-HPV serotypes. Seroprevalence for most HPV types was similar among men and women. While mucosal low-risk HPV seropositivity was found to significantly decrease with age, the prevalence of antibodies to mucosal HR antigens showed a general trend of increase with age. The lifetime number of sex partners was independently associated with mucosal HR-HPV seropositivity. Positive correlation of spousal seropositivity was observed for mucosal HPV but not for cutaneous HPV. Conclusions HPV infection was common in both men and women in rural China. HPV seroprevalence differed significantly with age, sexual behaviour and spousal infection status. These findings will be useful for evaluating and establishing HPV vaccination programmes.

Transmission of genital human papillomavirus infection in couples: a population-based cohort study in rural China

HPV transmission dynamics have rarely been studied in the general population, especially in China. We followed the genital HPV infection status of both partners in 874 couples aged 25-65 years from rural China for up to 7 bi-annual visits during 2009-2013. The positive HPV concordance and transmission rate for partners in a couple were evaluated and relevant risk factors were assessed. The concordance of any, oncogenic, and non-oncogenic HPV was 15.52%, 16.18% and 10.41%, respectively. Male-to-female transmission rate was 7.11, 12.13 and 4.77/1000 person months for any, oncogenic and non-oncogenic HPV respectively. The female-to-male transmission rate was 5.56, 2.37, and 17.01/1000 person months for any, oncogenic and non-oncogenic HPV respectively. The risk of male-to-female transmission was significantly higher than that of female-to-male transmission for oncogenic types. However, for non-oncogenic types, the risk of male-to-female transmission was significantly lower than that of female-to-male transmission. Younger couples, persistent infection with HPV, higher numbers of sexual partners and higher frequency of sexual intercourse were positively associated with HPV transmission in couples. Our results indicate that men in rural China play a more important role than men in western populations as a source of cervical oncogenic HPV infection in women.