线粒体DNA单倍群N9a与胃肠胰神经内分泌肿瘤发病风险的关系

摘 要：［目的］ 探讨线粒体DNA(mtDNA)非编码区D-loop区单核苷酸多态性及归属单倍体群与胃肠胰神经内分泌肿瘤（Gastroenteropancreatic neuroendocrine neoplasm,GEP-NEN）发病风险的关系。［方法］ 对130例GEP-NEN及148例正常健康对照组外周血mtDNA D-loop区序列进行DNA测序,通过与线粒体文库中的Revised Cambridge Reference Sequence (rCRS)比对分析两组人群中mtDNAD-loop区多态位点出现频率的差异。［结果］在GEP-NEN组和对照组中mtDNA D-loop区共检测到148个单核苷酸多态性（SNP）位点。筛选出23个SNP位点等位基因频率＞5% 的单核苷酸多态位点用于肿瘤发病风险分析。GEP-NEN组患者mtDNA D-loop区的73G、150T、151T、492C、16257A、16261T和16399G出现的频率明显高于对照组,差异均有统计学意义(P<0.05),其中150T、16257A、16261T均属于N9a单倍群。［结论］mtDNA D-loop区多态性位点线粒体D-loop区的突变分析对GEP-NEN高危人群具有诊断价值,线粒体DNA单倍体群N9a可能与GEP-NEN发病风险相关。     

红细胞补体受体1单核苷酸多态性与肝细胞癌发病风险的研究

目的 探讨红细胞补体受体1（CR1）单核苷酸多态性（SNP）与肝细胞癌（HCC）发病的关系。方法 收集102例HCC患者（HCC组）和98例健康体检者（对照组）的外周血样本,选取CR1的5个标签SNP位点（rs4844600 G＞A、rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C和rs9429945 C＞T）进行检测,分析两组的红细胞CR1基因各SNP位点基因型、等位基因及单体型的分布差异及其与HCC患病风险的关系。同时按照性别、年龄相匹配的原则分别从对照组和HCC组中选取52例和53例样本采用流式细胞术检测其红细胞CR1的几何平均荧光强度比值（GMFIR）。结果 两组rs4844600 G＞A基因型和等位基因分布的差异有统计学意义（P＜0.01）。CR1基因rs4844600 G＞A／GG基因型携带者患HCC的风险为非携带者的2.458倍（95％ CI：1.357～4.451）,GA基因型携带者患病风险是非携带者的0.404倍（95％CI：0.218～0.746）,其等位基因G携带者患病风险为非携带者的1.945倍（95％CI：1.183～3.199）。rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C、rs9429945 C＞T这4个SNP位点和rs11118167-rs3818361-rs17048010／TCT、TTC、CCT、TTT这4种单体型与HCC的患病风险无关（P＞0.05）。HCC组CR1的GMFIR水平为3.257±1.191,高于HCC组的2.652±0.789,差异有统计学意义（t=2.644,P=0.008）。结论 HCC患者红细胞免疫功能降低,CR1基因SNP位点rs4844600 G＞A与HCC发病关联。     

E-钙黏蛋白基因多态性与子宫颈癌发病风险的关系

目的：采用病例-对照研究,探讨CDH1（E-钙粘蛋白,E-cadherin）单核苷酸多态性（SNP）与中国北方妇女子宫颈癌发病风险的关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测243例子宫颈癌患者、323例健康对照的CDH1 -160C/A、-347G/GA两个位点的基因型及等位基因频率。结果：CDH1 -160C/A位点的基因型和等位基因型分布在患者组与健康对照组间差异无统计学意义（P>0.05）。CDH1 -347G/GA基因型和等位基因型总体分布在子宫颈癌患者组及健康对照组之间差异有统计学意义（P<0.05）。但与G/G基因型相比,携带GA等位基因的基因型（即G/GA+GA/GA基因型）可显著增加子宫颈癌的发病风险,OR值为2.66 (95%CI=1.48~4.80),同时有增加子宫颈癌的HPV16, 18型感染的趋势,OR值为1.979（95%CI=0.860~4.558）,子宫颈癌-160C/A、-347G/GA等位基因存在部分连锁不平衡（D′=0.793118,SD=0.0751）,单体型分析显示-160C/-347G是中国北方妇女常见单体型。与-160C/-347G单体型相比,-160A/-347GA单体型和-160C/-347GA单体型均也可增加该病的发病风险,OR为1.80（95％CI=1.10~2.94)和1.47（95％CI=1.10~1.96)。结论：与-347G/G基因型相比,携带GA等位基因的基因型（即G/GA+GA/GA基因型）可显著增加子宫颈癌的发病风险,增加子宫颈癌的HPV16, 18型感染的趋势。与-160C/-347G单体型相比,携带-160A/-347GA单体型和-160C/-347GA单体型都可以增加子宫颈癌的发病风险。     

rs4779584 C/T、rs4444235 T/C单核苷酸多态性与江苏泰州地区结直肠癌的发病风险研究

目的 了解单核苷酸多态性（SNP）与泰州地区人群中结直肠癌发病的关系。方法 收集泰州人民医院的76例结肠癌、84例直肠癌患者外周血样本作为疾病组,另选170例健康体检正常人群外周血样本作为对照组,选取与结直肠癌高度相关的SNP位点（rs4779584和rs4444235）进行检测,分析不同基因型和等位基因分布情况及其与结直肠癌总体和不同部位的患病风险。结果 两组rs4779584 C/T和rs4444235 T/C基因型分布均符合Hardy-Weinberg平衡。疾病组rs4779584 C/T和rs4444235 T/C的基因型和等位基因分布与对照组相比,差异均有统计学意义（P<0.05）。rs4779584 C/T中,以CC基因型为参照,CT和TT基因型与结直肠癌的患病风险无关联;以CC+CT基因型为参照,TT基因型的结直肠癌患病风险升高,以C等位基因为参照,T等位基因的结直肠癌患病风险升高,差异均有统计学意义（P<0.05）。rs4444235 T/C中,以TT、TT+TC基因型为参照,CC基因型的结直肠癌患病风险均升高;以T等位基因为参照,C等位基因的结直肠癌的患病风险升高,差异均有统计学意义（P<0.05）。结论 在江苏泰州地区人群中,rs4779584和rs4444235 位点SNP与结直肠肿瘤发病风险高度相关。     

SLC29A1基因C177G单核苷酸多态性与晚期胰腺癌吉西他滨化疗耐药及预后相关性的研究

摘 要：［目的］ 研究晚期胰腺癌患者SLC29A1基因177位点单核苷酸多态性(single nucleotide polymorphism,SNP)分布情况,并探索其与吉西他滨化疗耐药及与预后的关系。［方法］ 对晚期胰腺癌患者66例,抽提外周血标本DNA,应用DNA直接测序法明确SLC29A1基因177位点SNP序列,结合临床资料,分析SLC29A1基因SNP对晚期胰腺癌吉西他滨化疗耐药性及生存期的影响。［结果］ 66例患者SLC29A1基因C177G突变型为32例,其中吉西他滨化疗耐药者为25例,耐药率达78.1%;野生型34例,其中吉西他滨化疗耐药者17例,耐药率为50.0%。SLC29A1基因C177G突变型组胰腺癌患者吉西他滨化疗有效率明显较野生型组低,而耐药率明显较野生型组高,两者差异有统计学意义（P<0.05）。SLC29A1基因C177G突变型组胰腺癌患者的6个月生存率为72.3%,野生型组为83.7%,两者差异无统计学意义（P>0.05）;而前者的1年生存率为29．8%,后者为64.3%,差异有统计学意义（P<0.05）。［结论］ 晚期胰腺癌患者SLC29A1基因C177G SNP与胰腺癌患者吉西他滨化疗耐药及预后有相关性,可能成为有效预判胰腺癌患者吉西他滨化疗耐药及预后的敏感指标。     

雌激素受体α基因单核苷酸多态性与中国陕西地区汉族人群子宫内膜癌的相关性研究

目的:探讨雌激素受体α（estrogen receptor α,ERα）基因exon 4 的A908G、C926T、G933A、C975G 4个单核苷酸多态性（single nucleotide polymorphisms,SNPs）与子宫内膜癌易感性的相关性。方法:基于人群的病例-对照研究,通过PCR产物直接测序法鉴定中国陕西地区汉族89例子宫内膜癌与115例良性病变组织的这4个SNPs的基因型,采用Logistic回归模型分析两组基因型与等位基因频率的分布,确定SNP位点基因型与子宫内膜癌临床病理特征的相关性。结果:所有组织的ERα基因3个位点SNPs 均呈A908A、C926C、G933G野生型;而exon 4 C975G 位点SNP呈三种基因型形式,其频率分布在两组均达到Hardy-Weinberg遗传平衡(P>0.05),说明具有群体代表性。两组975G等位基因的发生频率分别为48.9%和51.7%,均＞1%,说明均存在exon 4 位点C975G SNP。两组间基因型与等位基因频率均无显著性差异（P>0.05）,说明位点C975G SNP与子宫内膜癌的危险性无关。ERα基因C975G SNP基因型与临床病理特征无相关性（P>0.05）。结论:首先在中国人子宫内膜癌和对照组中发现ERα基因exon 4 突变975G等位基因,发生频率分别为48.9%和51.7%,均＞1%,但C975G SNP与子宫内膜癌的危险性无关;且提示ERα基因的多态性可能具有肿瘤类型和种族的特异性。首先在中国人子宫内膜癌和对照组中未发现ERα基因exon 4位点A908G、C926T、G933A 3个SNPs,表明这些位点多态性在子宫内膜癌病人中并不常见。     

白细胞介素-6基因多态性与肺癌易感关联性的研究

目的：探讨白细胞介素-6（IL-6）基因多态性与肺癌易感性的关联性。方法：提取175例肺癌患者及200例正常对照者外周血基因组DNA,采用PCR方法扩增IL-6基因包含-174、-572、-597三个多态性位点的片段,采用限制性片段长度多态性方法（restriction fragment length polymorphism,RFLP）明确肺癌患者及正常对照者基因型。以非条件Logistic回归校正混杂因素,并进行多态性与肺癌风险关联性的统计学分析。结果：IL-6基因-174位点均为G/G型,未发现G/C和C/C型;-572位点存在C/C、G/C、G/G三种基因型;-597位点G/G型占99.2%,仅有3例为G/A型,未发现A/A型。肺癌组与对照组相比,基因分布（G/C基因型＋G/G基因型与C/C基因型相比）存在显著差异。分层分析显示：携带G/C及G/G基因型男性、40～70岁组和不吸烟肺癌组与正常对照组相比,肺癌发病风险降低。结论：IL-6基因启动子区-572位点多态性与肺癌易感性显著相关,携带G/C及G/G基因型的个体肺癌发病风险降低。     

一个家族性高胆固醇血症家系的基因突变筛查与评估

目的：对一个临床诊断的家族性高胆固醇血症（FH）家系进行全基因组外显子测序,以寻找该家系的致病基因。方法：采集该家系成员外周静脉血样本,检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）这四项指标,并提取白细胞DNA进行全基因组外显子测序,筛选出4个FH相关基因LDLR、APOB、PCSK9、LDLRAP1的单核苷酸多态性（SNP）位点情况并进行生物信息学分析,采用Polyphen-2和SIFT软件对SNP位点进行致病性分析。结果：该家系APOB基因的SNP位点rs676210、rs679899、c.10094A > T和c.9937C > G均可能与血脂增高有关,但这些位点均不与疾病表型共分离。经Polyphen-2和SIFT软件预测未发现LDLR,PCSK9和LDLRAP1基因的致病性变异。结论：该FH家系存在可能与血脂增高相关的APOB基因SNP位点,其功能尚需进一步的实验验证。     

一个家族性高胆固醇血症家系的基因突变筛查与评估

目的：对一个临床诊断的家族性高胆固醇血症（FH）家系进行全基因组外显子测序，以寻找该家系的致病基因。方法：采集该家系成员外周静脉血样本，检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）这四项指标，并提取白细胞DNA进行全基因组外显子测序，筛选出4个FH相关基因LDLR、APOB、PCSK9、LDLRAP1的单核苷酸多态性（SNP）位点情况并进行生物信息学分析，采用Polyphen-2和SIFT软件对SNP位点进行致病性分析。结果：该家系APOB基因的SNP位点rs676210、rs679899、c.10094A > T和c.9937C > G均可能与血脂增高有关，但这些位点均不与疾病表型共分离。经Polyphen-2和SIFT软件预测未发现LDLR，PCSK9和LDLRAP1基因的致病性变异。结论：该FH家系存在可能与血脂增高相关的APOB基因SNP位点，其功能尚需进一步的实验验证。     

ZO-1 SNPs与胃癌遗传易感性及预后*

目的:探讨中国福建地区汉族人群中ZO- 1 基因TJP1 4 个已知位点单核苷酸多态性（SNPs）与胃癌遗传易感性及进展和预后的相关性。方法:应用PCR-LDR法检测福建医科大学附属第一医院200 例健康体检个体及220 例原发性胃腺癌患者TJP1基因4 个SNP 位点的基因型。结果:福建地区汉族人群中,TJP-1 SNP rs 7179270 位点稀有等位基因C 的频率为0.2,而其他三个位点（rs 34771010,rs 28578444和rs 41280058）稀有等位基因频率为0.0。TJP1 基因SNP 位点rs 7179270 200 例对照组等位基因C、T 的频率分别为20% 和80% ,胃癌病例组等位基因C、T 的频率为32.6% 和67.4% ;CC、C/T和TT的基因型频率在对照组分别为4% 、32%和64% ,而在病例组为10.9% 、43.2% 和45.9% ,差异具有统计学意义（OR= 1.953,95%CI 1.425～2.677,P<0.001）。 TJP1 rs 7179270位点基因型与胃癌患者的性别、年龄、分化程度、浸润深度、淋巴结转移及手术后生存时间无显著相关（P>0.05）。 结论:TJP1rs 7179270 位点携带等位基因C 的CC和C/T基因型个体的胃癌患病风险提高,提示检测该位点基因型有助于评估胃癌的遗传易感性;TJP1 rs 7179270 位点的基因型频率与临床病理学参数及胃癌患者手术后生存时间无显著相关性,提示TJP1 rs 7179270 位点多态性可能不参与胃癌的进展和预后;TJP1 rs 34771010、rs 28578444和rs 41280058稀有等位基因频率为0.0,推测中国福建地区人群可能无这三个位点的多态性分布。      

Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma

Backgroud

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers and might be associated with cancer risk and disease outcome. We used a population-based series of esophageal squamous cell carcinoma (ESCC) patients for investigating the prediction power of SNPs in mitochondrial D-loop.

Methods

The D-loop region of mtDNA was sequenced for 60 ESCC patients recorded in the Fourth Hospital of Hebei Medical University between 2003 and 2004. The 5 year survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method.

Results

The SNP sites of nucleotides 16274G/A, 16278C/T and 16399A/G were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16278 and 16399 alleles were identified as independent predictors of ESCC outcome. The length of survival of patients with the minor allele 16278T genotype was significantly shorter than that of patients with 16278C at the 16278 site (relative risk, 3.001; 95% CI, 1.029 - 8.756; p = 0.044). The length of survival of patients with the minor allele 16399G genotype was significantly shorter than that of patients with the more frequent allele 16399A at the 16399 site in ESCC patients (relative risk, 3.483; 95% CI, 1.068 - 11.359; p = 0.039).

Conclusion

Genetic polymorphisms in the D-loop are independent prognostic markers for patients with ESCC. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups at high risk of a poor disease outcome.     

Identification of sequence polymorphisms in the mitochondrial displacement loop as risk factors for sporadic and familial breast cancer

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers, and the association of these SNPs with cancer risk and disease outcome has been exhaustively studied. We sequenced a region of approximately 1 kb flanking the majority of the D-Loop in the DNA from the blood of breast cancer patients and the controls to identify cancer risk-associated D-loop SNPs. The D-loop region of mtDNA was sequenced from 92 sporadic breast cancer patients, 60 familial breast cancer patients and 41 relatives, and 93 healthy controls. Paired and unpaired Student’s t tests were used as appropriate to determine the differences in SNP distribution within the D-loop region and in the number of SNPs per patient among the groups. The χ ² test was used to analyze dichotomous values, such as the presence or absence of an individual SNP among each group, and the clinical characteristics between every two groups. The distribution frequencies of 315C/Cinsert, 524C/del, 16247A/del, 16248C/del, 16249T/C, 16257C/A, 16258A/del, 16259C/del, 16262C/del, 16268C/del, 16279C/del, 16280A/del, 16297T/C, and 16300A/del were significantly different between sporadic breast cancer patients and the normal controls. The SNP sites at nucleotides 310, 315, and 16362 were identified as cancer risk-associated SNPs specific for familial breast cancer. The N haplogroup, defined as 489T, was identified as a specific risk-associated SNP for families of breast cancer patients by comparing familial breast cancer patients with their relatives. The analysis of genetic polymorphisms in the D-loop may help to predict cancer risk for familial breast cancer and thereby help to detect and refine therapeutic decisions earlier.     

Pathway-Affecting Single Nucleotide Polymorphisms (SNPs) in RPS6KA1 and MBIP Genes are Associated with Breast Cancer Risk

Background: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. Methods: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. Results: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). Conclusion: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population.  This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.     

Mitochondrial genotype and breast cancer predisposition

Breast cancer is the most commonly diagnosed cancer in women. Despite recent advances in breast cancer research, a comprehensive set of genetic markers of increased breast cancer risk remain elusive. Recently mitochondrial DNA (mtDNA) mutations have been found in many types of cancer, including breast cancer. To investigate the possible role of mitochondrial genetics in breast cancer predisposition and biology we analyzed the D-loop sequence of cancer patients and assigned mitochondrial haplogroup using RFLP analysis. We detected a significantly greater incidence of mtDNA polymorphisms T239C, A263G and C16207T and a significant lower incidence of A73G, C150T, T16183C, T16189C, C16223T, T16362C in patients with breast cancer compared to database controls. The mitochondrial haplogroup distribution in patients with breast cancer differs from a group of cancer-free controls and the general Polish population in that haplogroup I is over-represented in individuals with cancer. These findings suggest that mitochondrial haplogroup I as well as other polymorphic variants defined by SNPs in the D-loop may be associated with an increased risk of developing breast cancer.     

Clinical value of mitochondrial mutations in colorectal cancer.

PURPOSE: Prognostic factors that could select high-risk recurrence colorectal cancer patients and predict chemosensitivity are needed. Since mutations of mitochondrial DNA (mtDNA) have been described in different types of cancers and since they may play a role in response to anticancer agents, we investigated in a population-based series of colorectal cancer patients the clinical value of mtDNA mutations. PATIENTS AND METHODS: The displacement loop (D-loop) region of mtDNA was sequenced on a series of 365 patients recorded in the Digestive Cancer Registry of C?te-d'Or (France) between 1998 and 2000. Clinicopathologic characteristics were correlated to the presence of a D-loop mutation. Survival rates were compared with the log-rank test. A multivariate survival analysis was performed. RESULTS: D-loop mutations were found in 38.3% of the tumors. The 3-year survival rate was 53.5% in patients with D-loop mutation versus 62.1% in patients without (P = .05). After adjustment for age, stage, and microsatellite instability status, the relative risk of death in patients with D-loop mutation was 1.40 (95% CI, 1.02 to 1.93; P = .034) as compared with those without. In stage III colon cancers, adjuvant chemotherapy was beneficial only for patients without D-loop mutation (3-year survival, 78.3% v 45.4%, P < .02). In those with D-loop mutation who received adjuvant chemotherapy, the relative risk of death was 4.30 (95% CI, 1.23 to 15.00; P < .02). CONCLUSION: The D-loop region is a hotspot for somatic mutations in colorectal tumors. Moreover, presence of tumor D-loop mutation appears to be a factor of poor prognosis in colorectal patients and a factor of resistance to fluorouracil-based adjuvant chemotherapy in stage III colon cancers.     

Association of matrix metalloproteinase-8 gene variation with breast cancer prognosis

Animal and cell studies indicate an inhibitory effect of matrix metalloproteinase-8 (MMP8) on tumorigenesis and metastasis. We investigated whether MMP8 gene variation was associated with breast cancer metastasis and prognosis in humans. We first studied nine tagging single nucleotide polymorphisms (SNP) in the MMP8 gene in 140 clinically and pathologically well-characterized breast cancer patients. Four of the SNPs were found to be associated with lymph node metastasis, the most pronounced being a promoter SNP (rs11225395) with its minor allele (T) associating with reduced susceptibility to lymph node metastasis (P = 0.02). This SNP was further evaluated for association with cancer relapse and survival among a cohort of approximately 1,100 breast cancer patients who had been followed for cancer recurrence and mortality for a median of 7.1 years. The T allele was associated with reduced cancer relapse and greater survival, particularly among patients with earlier stage cancer. Among patients of tumor-node-metastasis stage 0 to II, the adjusted hazard ratio of disease-free survival was 0.7 [95% confidence interval (95% CI), 0.5-0.9] for patients carrying T allele compared with those homozygous for the C allele (P = 0.02). In vitro experiments showed that the T allele had higher promoter activity than the C allele in breast cancer cells. Electrophoretic mobility shift assays showed binding of nuclear proteins to the DNA sequence at the SNP site of the T allele but not that of the C allele. The data suggest that MMP8 gene variation may influence breast cancer prognosis and support the notion that MMP8 has an inhibitory effect on cancer metastasis.     

Association of mtDNA D-Loop Polymorphisms with Risk of Gastric Cancer in Chinese Population

The aim of present study was to evaluate the association of common polymorphisms detected in mitochondrial DNA (mtDNA) D-loop region (mononucleotide repetitive D310, single nucleotide polymorphism (SNP) D16521) with susceptibility to gastric cancer (GC) in northwestern Chinese population. A total of 180 GC patients and 218 healthy controls were investigated by using PCR- denaturing high performance liquid chromatography (DHPLC) assay. Genotype and allele distributions and haplotype construction were analyzed in case–control study. We found D310 and D16521 heteroplasmy were significantly different between GC cases and controls (p < 0.05), and D16521 homoplasmy showed association with histological grade of GC (p < 0.05). Haplotype 7C/T, 8C/C and 9C/C had significant association with GC risk implied from analysis of D310 and D16521. Taken together, these findings suggested that mtDNA D-Loop polymorphisms and haplotypes may contribute to genetic susceptibility to GC in Chinese population.