STAT4基因多态性与乙型肝炎病毒感染相关性肝细胞癌易感性的关系

目的 分析信号传导与转录激活因子4(STAT4)基因多态性与中国人群肝细胞癌(HCC)易感性的关系.方法 154例乙型肝炎病毒(HBV)感染相关HCC为肝癌组,135例性别及年龄匹配的HBsAg阳性患者为非肝癌组.采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP),检测STAT4 rs7574865位点的基因型,并经测序分析验证.Logistic回归分析比较不同基因型与HCC易感风险的关系.结果 STAT4 rs7574865位点3种基因型TT、GT、和GG型在肝癌组的分布频率分别是5.8％ (9/154)、37.0％ (57/154)和57.1％ (88/154),在非肝癌组分别是8.9％(12/135)、43.7％ (59/135)和47.4％ (64/135).各基因型在两组间差异无统计学意义(P＞0.05);以TT基因型作参照,携带rs7574865 GG型的个体HCC患病风险差异无统计学意义(OR=1.833,95％ CI=0.729～4.611,P=0.221).结论 STAT4 rs7574865多态性位点可能与中国人群HBV感染相关HCC易感性无明显相关性.     

肝癌病例中XRCC1基因多态性与环境因素的交互作用分析

目的：研究某些环境因素与X射线修复交叉互补组1（XRCC1）基因多态性间交互作用对肝细胞癌（HCC）发生危险性的影响。方法：采用单纯病例研究方法,调查500例HCC患者所接触的相关环境因素,用荧光实时定量PCR方法检测XRCC1—280、XRCC1—194和XRCC1—399单核苷酸多态性。结果：XRCC1—280与乙肝e抗体对HCC的发生有正相乘交互作用（P=0．047,OR=1．809,95％CI：1．007～3．249）;XRCC1—194与饮酒对HCC的发生有正相乘交互作用（P=0．041,OR=1．496,95％CI：1．016～2．204）;XRCC1—194与乙肝表面抗体阳性对HCC的发生有负相乘交互作用（校正后,P=0．045,OR=1．737,95％CI：1．013～2．979）。未发现XRCC1—399基因多态性与相关环境因素之间存在交互作用。结论：携带XRCC1—194突变等位基因与饮酒、乙肝表面抗体阳性对HCC可能存在交互作用;携带xRCC1—280突变等位基因与乙肝e抗体对HCC可能存在交互作用。     

p53codon72单核苷酸多态性与肝细胞癌发病风险的关系

[目的]探讨广西地区p53基因codon72单核苷酸多态性(SNP)与肝细胞癌(HCC)发病风险的关系。[方法]采用TaqMan MGB探针等位基因分型技术对985例肝癌病例和相匹配的992例非肿瘤对照的p53 codon72(Arg>Pro,rs1042522)基因型进行检测,并分析该SNP与肝癌发病风险的关系。[结果]p53 codon72多态性与肝癌发病风险之间无统计学关联(Arg/Pro:校正OR=1.15,95%CI:0.83～1.59;Pro/Pro:校正OR=1.16,95%CI:0.80～1.68;Arg/Pro+Pro/Pro:校正OR=1.15,95%CI:0.85～1.57)。按是否吸烟、饮酒、HBV和HCV感染分层分析,亦未发现p53 codon72多态性与肝癌发病风险有关。但基因—环境交互作用显示,该基因多态性与吸烟、饮酒和HBV感染存在交互作用,OR值分别为2.42(95%CI:1.47～3.97)、2.96(95%CI:1.82～4.80)和62.74(95%CI:34.39～114.46)。[结论]p53codon72的单独效应可能与肝癌易感性无关联,但该SNP与吸烟、饮酒和HBV感染存在基因—环境交互作用,增加肝癌的发病风险。     

miRNA-196a2 rs116149131基因多态性与胃癌患病风险的Meta分析

目的 探讨microRNA（miRNA）-196a2 rs116149131基因多态性与胃癌易感性的关系。方法 计算机检索PubMed、EMBASE、Cochrane library、中国知网、维普、万方及中国生物医学文献（CBD）等数据库中2016年3月1日之前关于miRNA-196a2 rs116149131基因多态性与胃癌易感性的相关研究。按纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,采用Stata 12.0软件进行Meta分析,计算合并OR值及其95％CI,并进行发表偏倚评估及敏感性分析。结果 共纳入9篇文献,包括3992例患者和5699例对照。Meta分析结果显示,miRNA-196a2 rs116149131基因多态性与胃癌易感性无明显相关性。按种族进行亚组分析结果显示,rs116149131基因多态性在杂合子模型中显著增加高加索人种胃癌患病风险（CT vs. TT：OR=1.93,95％CI：1.35～2.75,P＜0.05）;而在亚洲人种中未发现该位点多态性与胃癌易感性有关。根据对照组人群的来源进行亚组分析结果显示,在以医院和以人群为基础的研究中均未发现有与胃癌易感性相关的等位基因或者基因型。在T＜C亚组中,显性基因模型（CT+CC vs. TT：OR=1.40,95％CI：1.10～1.77,P=0.005）、纯合子模型（CC vs. TT：OR=1.59,95％CI：1.22～2.06,P=0.001）和杂合子模型（CT vs. TT：OR=1.33,95％CI：1.04～1.70,P=0.025）中发现rs116149131基因多态性与胃癌患病风险存在关联性;在等位基因模型和隐性基因模型中并未发现关联性。在T＞C组未发现rs116149131多态性与胃癌患病风险存在关联性。结论 miRNA-196a2 rs116149131基因多态性与胃癌患病风险无关联性,但存在种族差异。     

广西地区人群TNF-α基因启动子区多态性与肝癌的易感性研究

背景与目的:原发性肝细胞癌(hepatocellular carcinoma,HCC)是一种高度恶性的肿瘤,TNF-α参与了HCC的病理发生、发展过程。本研究探讨广西地区人群TNF-α基因启动子区-1031C/T(rs1799964)和-308A/G(rs1800629)的单核苷酸多态性及其与环境因素的交互作用与HCC遗传易感性的关系。方法:采用以医院为基础的病例对照研究,选择来自于广西地区的新发HCC患者620例,相同地区年龄、性别和民族频数匹配的非肿瘤患者625例。采用TaqMan MGB实时荧光定量PCR方法对TNF-α基因-1031位点和-308位点进行基因分型,比较不同基因型与HCC患病风险的关系,并探讨基因-环境的交互作用对患病风险的影响。结果:TNF-a基因-1031位点3种基因型TT、TC、CC在病例组和对照组中分布差异无统计学意义(P>0.05),与TT基因型患者相比,TC或CC基因型者患HCC的风险并无显著增加(P>0.05)。TNF-α基因-308位点GG、GA、AA基因型在病例组和对照组中分布差异无统计学意义(P>0.05),与GG基因型患者相比,GA或AA基因型者患HCC的风险并无显著增加(P>0.05)。叉生分析结果表明,TNF-α基因-1031位点单核苷酸多态性与吸烟、饮酒及HBV感染等环境因素在HCC发生中存在交互作用,OR分别为3.367、4.709和25.433;-308位点与吸烟、饮酒、食鱼生及HBV感染等环境因素在HCC发生中存在交互作用,OR分别为3.720、5.316、24.975和19.822。结论:TNF-α基因-1031位点和-308位点单核苷酸多态性在HCC发生过程中,可能无独立的危险作用,但与吸烟、饮酒、食鱼生及HBsAg阳性等环境因素交互作用能增加HCC的发病风险。     

COX-2基因单核苷酸多态性与肝细胞癌关联的研究

目的:探讨广西地区COX-2基因-1195G>A(rs689466)和8473T>C(rs5275)位点单核苷酸多态性与肝细胞癌(HCC)遗传易感性的关系。方法:采用以医院为基础的病例对照研究方法。研究对象为780例经组织学确诊的HCC患者和780例相同地区、年龄、性别和民族频数匹配的非肿瘤患者。运用Taq Man MGB探针等位基因分型技术进行COX-2基因单核苷酸多态性的检测,以χ2检验和非条件Logistic回归模型分析比较病例和对照两组间各位点基因型频率分布的差异及其与HCC患病风险的关系,并进一步探讨基因-环境的交互作用对HCC患病风险的影响。结果:COX-2基因单位点-1195G>A或8473T>C多态与HCC患病风险无统计学相关性(显性模型下SNP-1195G>A:校正OR=1.32,95%CI:0.94~1.85;SNP8473T>C:校正OR=0.87,95%CI:0.64~1.18)。分层分析显示,显性模型下COX-2基因-1195G>A位点GA+AA基因型增加年龄<55岁者患HCC的风险(校正OR=1.56,95%CI:1.03~2.37),而8473T>C位点TC+CC基因型可降低女性患HCC的风险(校正OR=0.50,95%CI:0.25~0.99)。进一步交互作用分析显示,COX-2基因-1195G>A位点与年龄、8473T>C位点与性别分别存在交互作用(P=0.002;P=0.007)。结论:COX-2基因-1195G>A或8473T>C位点SNP的单独效应可能与HCC易感性无关联,但是-1195G>A与年龄、8473T>C位点与性别存在交互作用,影响HCC的患病风险。     

MTMR3基因多态性与非吸烟者肺癌易感性

目的 位于染色体22q12.2区域的MTMR3 (myotubularin related protein 3)基因是调控肌维管束蛋白表达的基因,MTMR3基因过度表达与肿瘤等疾病发生有关.本研究旨结合表达数量性状(expression Quati tatire Trait Loci,eQTL)信息探讨MTMR3基因多态性与非吸烟者肺癌易感性的关系,为探究肺癌的发病机制提供依据.方法 对肺癌易感区域22q12.2进行连锁不平衡和eQTL分析,筛选具有调控基因表达的致病位点并预测其调控的基因.本研究采用病例对照研究方法,病例为2013-03-05-2014-12-30辽宁省肿瘤医院(96例)、中国医科大学附属第一医院(92例)、中国医科大学附属第四医院(90例)、沈阳军区总医院(95例)和人民解放军沈阳二0二医院(88例)5所三甲级医院的原发性肺癌患者461例(病例组),同期社区中健康对照472名(对照组).应用TaqMan基因分型技术对rs36605位点进行基因分型.采用t检验比较年龄在病例组与对照组间分布的差异,采用x2检验比较性别、各基因型以及各环境暴露因素在病例组与对照组间分布的差异,应用Logistic回归计算OR值及其95％置信区间(CI).结果 经eQTL分析得到rs36605位点是MTMR3基因的一个顺式eQTL,rs36605位点可能与MTMR3基因的表达有关.以TT基因型为参照,AT基因型(OR=0.81,95％CI为0.60～1.10,P=0.178)和AA基因型(OR=1.85,95％CI为0.61～5.59,P=0.276)与肺癌的患病风险无统计学关联.也未发现在显性模型(OR=0.85,95％CI为0.63～1.15,P=0.291)以及隐形模型(OR=1.94,95％CI为0.64～5.86,P=0.238)中存在此关联.试验验证了烹饪油烟暴露增加了肺癌的患病风险,调整OR=1.61,95％CI为1.06～2.45,P=0.025,但未发现烹饪油烟暴露与rs36605位点多态性之间存在交互作用,P＞0.05.结论 试验未发现,22q12.2区域内的rs36605位点多态性与非吸烟者肺癌的易感性有关,尚不能得到MTMR3基因多态性与非吸烟者肺癌的易感性有关.     

CTLA-4基因多态性与膀胱癌易感性的相关性及基因-环境交互作用的研究北大核心

目的:探讨细胞毒性T淋巴细胞抗原4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)基因rs733618、rs5742909、rs231775位点单核苷酸多态性与膀胱癌的相关性。方法:收集188例膀胱癌患者和188名健康对照人群的人口学及生活行为方式资料,采集研究对象5 mL外周血提取DNA,通过imLDR技术对rs733618、rs5742909、rs231775位点进行基因分型,观察各位点基因型在病例组和对照组之间的分布差异,使用条件Logistic回归分析各基因型与膀胱癌发病风险的关系,并基于GMDR探究基因与环境的交互作用。结果:CTLA-4 rs733618位点基因型和等位基因频率在病例组和对照组间的分布差异均无统计学意义(P>0.05);rs231775位点基因型和等位基因频率在两组的分布差异均有统计学意义(P<0.05),但rs733618、rs5742909、rs231775三个位点与患膀胱癌的风险关系均未达到统计学差异(P>0.05)。吸烟是膀胱癌的独立危险因素(OR=2.982,95%CI:1.594~5.577)。GMDR分析表明rs231775位点、吸烟史和文化程度间存在交互作用(OR=3.44,95%CI:1.82~6.53)。结论:CTLA-4基因rs733618、rs5742909、rs231775位点多态性与中国人群膀胱癌患病风险可能无关,其中rs231775位点与吸烟史及文化程度因素存在交互作用,增加膀胱癌患病风险。     

PTEN基因多态性与河北省高发区食管鳞状细胞癌发病风险的关系

目的：PTEN作为押癌基因，具有脂质磷酸酶和蛋白磷酸酶的活性，在调节细胞生长、分化和凋亡方面起重要作用．位于胛EN基因第4内含子的一个插入性多态ⅣS4（-／＋）可能通过不同剪切来影响其基因表达。本研究旨在探讨河北省食管癌高发区人群中这一常见多态与食管鳞状细胞癌发病风险的关系。方法：采用基于人群的病例一对照研究。以聚合酶链反应-限制性片段长度多态性方法进行基因分型，分析来自食管癌高发区的350例食管癌患者和634例健康对照者的FrrEN基因多态性。结果：具有上消化道肿瘤家族史可明显增加食管癌的发病风险，经性别、年龄和吸烟状况校正的OR值为1．73（95％CI=1．29～2．32）。PTENIVS4基因型在食管癌患者和健康对照中总体分布无显著性差异。与ⅣS4-／-基因型相比携带ⅣS4＋／＋基因型显著降低食管癌发病风险，校正的OR值为0．64（95％CI：0．44加．94）。根据吸烟状况和上消化道肿瘤家族史进行分层分析，发现在有上消化道肿瘤家族史个体中携带ⅣS4-／＋基因型降低食管癌的发病风险（校正OR=0．55，95％CI=0．34—0．90），而在吸烟个体、非吸烟个体及上消化道肿瘤家族史阴性个体中PTENⅣS4-／＋、＋／＋基因型均不影响食管鳞状细胞癌的发病风险。结论：PTENIVS4＋／＋基因型是河北省食管癌高发区食管鳞状细胞癌发生的保护性因素，此外PTENⅣS4-／＋基因型仅降低家族集聚性食管癌的发病风险.     

DNA双链断裂修复基因XRCC4多态性与肺癌易感性的关系

目的:探讨DNA双链断裂修复基因X-射线修复交叉互补4(X-ray repair cross-complementing 4, XRCC4)基因单核甘酸多态性(single nucleotide polymorphism, SNP)与肺癌发生风险的关系.方法:采用病例-对照研究的方法,应用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)技术和TaqMan探针基因分型技术对781例肺癌患者和781健康志愿者(作为对照)进行XRCC4 rs6869366、rs3734091和rs1056503多态性的检测;结合PCR和定点突变技术,分别构建含有XRCC4基因启动子rs6869366位点不同等位基因的重组质粒,以双荧光素酶报告系统检测SNP位点碱基突变对启动子活性的影响.结果:XRCC4 rs6869366位点携带G等位基因的基因型(T/G+G/G)可显著增加肺癌的患病风险[比值比(odds ratio, OR)=1.607, 95%可信区间(confidence interval,CI): 1.138~2.270];rs6869366与rs3734091存在连锁不平衡,携带由其构建的单体型GC或单体型对TC/GC者患肺癌的风险增加(OR=1.993,95%CI:1.194~3.329;OR=2.013,95%CI:1.174~3.452);含rs6869366不同等位基因的启动子转录活性差异无统计学意义.结论:XRCC4 rs6869366位点多态性与肺癌的易感性有关,其影响机制还需进一步研究.     

A case–control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy

Objectives: We carried out a case–control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC).Methods: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity.Results: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2–4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.6–1.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6–6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake.Conclusions: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.     

Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S

BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites.     

A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma

CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.     

Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma

Environmental risk factors cause DNA damages. Imprecise DNA repair leads to chromosome aberrations, genome destabilization and hepatocarcinogenesis. Ku is a key DNA double-strand break repair protein. We hypothesized that the genetic variants in Ku subunits encoding genes, XRCC5/XRCC6, may contribute to hepatocellular carcinoma (HCC) susceptibility. We genotyped 13 common single nucleotide polymorphisms (SNPs) in XRCC5 and XRCC6 and evaluated their associations with HCC risk in 689 pathologically confirmed cases and 690 cancer-free controls from a Chinese population. We found that a significantly reduced risk for HCC was associated with XRCC5 rs16855458 [odds ratio (OR)=0.59; 95% confidence interval (CI)=0.43-0.81; CA+AA versus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR=2.02; 95% CI=1.42-2.86; TA+AA versus TT) even after Bonferroni correction (Pcorrected=0.026 and 0.002, respectively). The effects of rs16855458 (OR=0.57; 95% CI=0.37-0.86, P=0.008) and rs9288516 (OR=1.86; 95% CI=1.19-2.90, P=0.007) were more significant in hepatitis B surface antigen-infected subjects than non-infected subjects. The haplotype-based analysis revealed that in XRCC5, AA in block 1 (OR=0.63; 95% CI=0.48-0.83) and CGGTT in block 2 (OR=0.52; 95% CI=0.39-0.69) were associated with decreased HCC risk (Pcorrected=0.013 and <0.001, respectively). The aforementioned two SNPs exhibited a significant cumulative risk effect (Ptrend<0.001). Additionally, potential interaction among XRCC5 rs9288516 and rs2267437, rs5751131 in XRCC6 was indicated by the multifactor dimensionality reduction analysis. In conclusion, XRCC5 variants may play a role in determining individual's HCC susceptibility, which warranted validation in larger studies.     

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case-control study in Taiwan

This study was conducted to investigate the modifying effect of glutathione S-transferase (GST) M1 and T1 polymorphisms on aflatoxin-induced hepatocarcinogenesis among chronic hepatitis B virus surface antigen (HBsAg) carriers. A total of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1997 were identified and individually matched to one or two HBsAg-positive controls on age, gender, residence and date of recruitment from the same cancer screening cohort in Taiwan. Blood samples were tested for hepatitis B and C viral markers by enzyme immunoassay and for aflatoxin B(1) (AFB(1))-albumin adducts by competitive enzyme-linked immunosorbent assay. GSTM1 and GSTT1 genotypes were determined by PCR. There was a statistically significant relationship between detectable levels of AFB(1)-albumin adducts in serum and risk of HCC among chronic HBsAg carriers, with an adjusted odds ratio (OR) of 2.0 [95% confidence interval (CI) 1.1-3.7]. In addition, the effect of aflatoxin exposure on HCC risk was more pronounced among chronic HBsAg carriers with the GSTT1 null genotype (OR 3.7, 95% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB(1)-albumin adduct level and GSTT1 genotype was statistically significant (P = 0.03). For GSTM1 the effect of aflatoxin exposure on HCC risk in those with the null genotype was also greater (adjusted OR 2.8, 95% CI 1.0-7.8) than in those with the gene present (adjusted OR 1.8, 95% CI 0.8-4.5), but the difference was not significant (P = 0.91). Notably, when the interaction between aflatoxin exposure and GSTT1 genotype was considered, aflatoxin exposure by itself was not a significant determinant of HCC risk among chronic HBsAg carriers. These results demonstrate the importance of gene-environment interactions in the multifactorial development of HCC.     

Relationship of hepatocellular carcinoma to soya food consumption: a cohort-based, case-control study in Japan

To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case-control study within a cohort of Japanese A-bomb survivors. We compared the prediagnosis consumption of isoflavone-rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist-confirmed cases of HCC diagnosed in 1964-1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue-based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29-0.95) and 0.5 (95% CI 0.20-0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14-1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20-3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk.     

Betel quid chewing as a risk factor for hepatocellular carcinoma: a case-control study

The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC) was evaluated in a case-control study including 263 pairs of age- and sex-matched HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) were determined, and standardized personal interview conducted using a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence interval (CI), 1.74-6.96), HBsAg (OR, 16.69; 95% CI, 9.92-28.07), anti-HCV (OR, 38.57; 95% CI, 18.15-81.96), and educational duration of less than 10 years (OR, 1.71; 95% CI, 1.05-2.78) are independent risk factors of HCC. In addition, there was an additive interaction between betel quid chewing and chronic infection with either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing increased, or amount of betel quid consumed (each P for trend < 0.0001).