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      Patrilineal Background of Esophageal Cancer and Gastric Cardia Cancer Patients in a Chaoshan High-Risk Area in China

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          Abstract

          The Taihang Mountain range of north-central China, the Southern region area of Fujian province, and the Chaoshan plain of Guangdong province are 3 major regions in China well known for their high incidence of esophageal cancer (EC). These areas also exhibit high incidences of gastric cardia cancer (GCC). The ancestors of the Chaoshanese, now the major inhabitants in the Chaoshan plain, were from north-central China. We hypothesized that EC and GCC patients in Chaoshan areas share a common ancestry with Taihang Mountain patients. We analyzed 16 East Asian-specific Y-chromosome biallelic markers (single nucleotide polymorphisms; Y-SNPs) and 6 Y-chromosome short tandem repeat (Y-STR) loci in 72 EC and 48 GCC patients from Chaoshan and 49 EC and 63 GCC patients from the Taihang Mountain range. We also compared data for 32 Chaoshan Hakka people and 24 members of the aboriginal She minority who live near the Chaoshan area. Analysis was by frequency distribution and principal component, correlation and hierarchical cluster analysis of Y-SNP. Chaoshan patients were closely related to Taihang Mountain patients, even though they are geographically distant. Y-STR analysis revealed that the 4 patient groups were more closely related with each other than with other groups. Network analysis of the haplogroup O3a3c1-M117 showed a high degree of patient-specific substructure. We suggest that EC and GCC patients from these 2 areas share a similar patrilineal genetic background, which may play an important role in the genetic factor of EC and GCC in these populations.

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          Most cited references16

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          Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China.

          Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCC) were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian.
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            Genome-wide association studies of gastric adenocarcinoma and esophageal squamous cell carcinoma identify a shared susceptibility locus in PLCE1 at 10q23

            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.
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              Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

              The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                10 December 2013
                : 8
                : 12
                : e81670
                Affiliations
                [1 ]Institute of Clinical Pathology & Department of Pathology, Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, China
                [2 ]Department of Pathology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
                [3 ]Department of General Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
                Kagoshima University Graduate School of Medical and Dental Sciences, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MS SL BH. Performed the experiments: SL BH HH. Analyzed the data: SL BH. Contributed reagents/materials/analysis tools: XL GC WL DG GZ JW ZY XL. Wrote the paper: SL.

                Article
                PONE-D-13-23909
                10.1371/journal.pone.0081670
                3858265
                24339953
                ddf20665-e2ff-4e56-abf1-71bbcf09006c
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 June 2013
                : 17 October 2013
                Page count
                Pages: 10
                Funding
                This study was sponsored by NSFC-Guangdong joint fund key project (U1132004), NSFC (31171226, 81101548), Guangdong International Cooperative Technical Innovation Platform (Certificates gihz1106), and NSF Guangdong Province (S2011020002393). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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