CN108624682A - 罹癌风险评估方法 - Google Patents
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- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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Abstract
本发明提供一种罹癌风险评估方法,是用在评估一受测者罹患特定癌症的风险高低程度,该方法包含有以下步骤:S1.取得该受测者的一检体;S2.选定一目标癌症,该目标癌症对应多个单核苷酸多型性检测程序;S3.依据每一该单核苷酸多型性检测程序检测该检体,并对应每一该单核苷酸多型性检测程序产生一风险基值;以及S4.统计每一该单核苷酸多型性检测程序产生的该风险基值,并依据统计结果评估该受测者罹患对应癌症的一罹癌风险等级。藉由本发明的方法,可预先评估受测者诱发特定癌症的风险,而能尽早提供预防方针。
Description
技术领域
本发明关于一种罹癌风险评估方法,尤指一种通过检验受测者的检体与至少一组癌症关联基因群的相关性,并藉以评估受测者罹癌风险的方法。
背景技术
常见的恶性肿瘤有大肠癌、直肠癌、肝癌、乳癌等。多数癌症的症状在早期并不明显,患者甚至不会感觉到任何异样,直到肿瘤细胞逐渐成长,患者才开始出现疼痛、食欲下降、疲乏无力等征状。但因患者患病初期并未感到不适,就医时肿瘤往往已长成相当棘手的尺寸,延误了最佳的治疗时间。因此,如何在癌症初期加以预防,是目前医界共同努力的方向。
具体而言,癌症的成因除了后天的生活环境、习惯等因素外,先天的染色体组成决定了人类罹患癌症风险的高低,在某些后天条件(如摄入过多致癌物质、生活作息不正常等…)影响下,细胞可能会由DNA转译出具有癌症启动机制的mRNA(messenger RNA,信使RNA),并在mRNA通过细胞核膜合成蛋白质,使得正常的细胞转变为癌细胞,并不断增生而成。是以,若能检测受测者是否具有容易构成特定癌症的基因组合,便可得知受测者患上某种癌症的风险。
现今已有一种产生核酸定序(DNA Sequencing)检验方法,可得知受测者患有遗传性疾病的风险高低,并采取适当的预防方针。然而这类检测套组仅能用在评估较罕见且特殊性高的遗传性疾病,相对而言,各类癌症普遍性较高,因此评估时需要考虑多个基因片段的交互作用,方能得到高确率的评估结果。是以,习用技术实有改善的必要。
发明内容
本发明的目的,在于解决先前技术无法适用在评估罹癌风险的问题。
为达上述目的,本发明提供一种罹癌风险评估方法,是用在评估一受测者罹患特定癌症的风险高低程度,其特征在于,该方法包含有以下步骤:S1.取得该受测者的一检体;S2.选定一目标癌症,该目标癌症对应多个单核苷酸多型性检测程序;S3.依据每一该单核苷酸多型性检测程序检测该检体,并对应每一该单核苷酸多型性检测程序产生一风险基值;S4.统计每一该单核苷酸多型性检测程序产生的该风险基值,并依据统计结果评估该受测者罹患对应癌症的一罹癌风险等级。
进一步地,该目标癌症是选自大肠直肠癌、肺癌、肝癌、乳癌、胃癌、口腔癌或普遍性癌症其中一者。
进一步地,该目标癌症为大肠直肠癌,则该单核苷酸多型性检测程序是包含有:XRCC1、NAT2、ERCC1检测程序,其中该XRCC1检测程序是判定该检体在基因位点XRCC1:rs25487的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:AA>AG>GG;其中该NAT2检测程序是判定该检体在基因位点NAT2(rs1799930)的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:AA=AG>GG;其中该ERCC1检测程序是判定该检体在基因位点ERCC1(rs11615)的碱基是否为C,若该位点为碱基T则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:TT>CT>CC。
进一步地,该目标癌症为肺癌,则该单核苷酸多型性检测程序是包含有:NAT2、CYP2D6检测程序,其中该NAT2检测程序是判定该检体在基因位点NAT2:rs1799930的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肺癌的该风险基值呈下述关系:AA=AG>GG;其中该CYP2D6检测程序是判定该检体在基因位点CYP2D6:rs1065852的碱基是否为T,若该位点为碱基C则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肺癌的该风险基值呈下述关系:CC>CT>TT。如权利要求2项所述的罹癌风险评估方法,其中该目标癌症为肝癌,则该单核苷酸多型性检测程序是包含有:EGF、TNF检测程序,其中该EGF检测程序是判定该检体在基因位点EGF:rs4444903的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肝癌的该风险基值呈下述关系:GG>AG>AA;其中该TNF检测程序是判定该检体在基因位点TNF:rs1800629的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肝癌的该风险基值呈下述关系:AA=AG>GG。
进一步地,该目标癌症为乳癌,则该单核苷酸多型性检测程序是包含有:BRCA1、BRCA2、HER2检测程序,其中该BRCA1检测程序是判定该检体在基因位点BRCA1(rs16941)的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>AG>AA;其中该BRCA2检测程序是判定该检体在基因位点BRCA2:rs144848的碱基是否为T,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>GT>TT;其中该HER2检测程序是判定该检体在基因位点HER2rs1136201的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>AG>AA。
进一步地,该目标癌症为胃癌,则该单核苷酸多型性检测程序是包含有:PLCE1、MDM2检测程序,其中该PLCE1:rs2274223检测程序是判定该检体在基因位点PLCE1:rs2274223的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患胃癌的该风险基值呈下述关系:GG>AG>AA;其中该MDM2检测程序是判定该检体在基因位点MDM2:rs2279744的碱基是否为T,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患胃癌的该风险基值呈下述关系:GG>GT=TT。
进一步地,该目标癌症为口腔癌,则该单核苷酸多型性检测程序是包含有:MMP1、ADH1B检测程序,其中该MMP1:rs1799750检测程序是判定该检体在基因位点MMP1:rs1799750的碱基是否为G,若该位点发生删除反应则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患口腔癌的该风险基值呈下述关系:-/->-/G>GG;其中该ADH1B检测程序是判定该检体在基因位点ADH1B:rs1229984的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患口腔癌的该风险基值呈下述关系:GG>AG>AA。
进一步地,该目标癌症为普遍性癌症,则该单核苷酸多型性检测程序是包含有:P53、KRAS检测程序,其中该P53检测程序是判定该检体在基因位点P53:rs1042522的碱基是否为G,若该位点为碱基C则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患普遍性癌症的该风险基值呈下述关系:CC>CG>GG;其中该KRAS检测程序是判定该检体在基因位点KRAS:rs2955407的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患普遍性癌症的该风险基值呈下述关系:GG=AG>AA。
进一步地,该风险基值是依据以下步骤决定:S5.收集多个组经由该单核苷酸多型性检测程序取得的参考数据,该参考数据包含有多个患有该目标癌症者的基因型,以及多个未患有该目标癌症者的基因型;S6.定义多数患者的基因型为高度风险,并定义多数未患有该目标癌症者的基因型为低度风险,其余基因型为中度风险。
进一步地,在该步骤S4中包含有以下步骤:S41.设定每一该风险基值的参考值,该风险基值最高者为3、最低者为1、其他为2,并取得该些风险基值的平均值;S42.若前述平均值为1,则判定该罹癌风险等级为低风险;若前述平均值大于2,则判定该罹癌风险等级为高风险;其余情况则判定该罹癌风险等级为中风险。
是以,本发明较先前技术具有以下有益功效:
本发明可预先评估受测者罹患何种癌症的风险较高,并依据风险等级归类,进而给予受测者生活建议或是预防性治疗,以利在癌症病发前早期予以抑制。
附图说明
图1:为本发明的方法流程图。
图2及图3:为本发明一种实施态样的基因鉴别坐标图。
其中,附图标记为:
纵轴区块.10a、10b 横轴区块.20a、20b
中性区块.30a、30b 步骤.S1~S6
具体实施方式
关于本发明的技术内容,请参照图1所示,本发明提供一种罹癌风险评估方法,是用在评估一受测者罹患特定癌症的风险高低程度。本发明主要目的在于评估受测者罹患特定癌症的风险高低,而可依据评估结果就风险较高项目向受测者提供方针或建议,达到降低癌症发生机率的目的。
具体而言,所述的方法包含有以下步骤:
S1.取得该受测者的一检体。本发明中,该检体可为口腔黏膜等。
S2.选定一目标癌症,该目标癌症对应多个单核苷酸多型性检测程序;本步骤中,该目标癌症是选自大肠直肠癌、肺癌、肝癌、乳癌、胃癌或口腔癌其中一者。每一该目标癌症是对应多个单核苷酸多型性(Single Nucleotide Polymorphism,SNP)。
S3.依据每一该单核苷酸多型性检测程序检测该检体,并对应每一该单核苷酸多型性检测程序产生一风险基值;本发明中,是依该检体发生SNP的基因型的不同,而将该风险基值分为低、中、高三种程度。
S4.统计每一该单核苷酸多型性检测程序产生的该风险基值,并依据统计结果评估该受测者罹患对应癌症的一罹癌风险等级。
本发明的用语「风险基值」是指对每一种该单核苷酸多型性检测程序所测出的不同基因型别,可能会对应不同程度的罹癌风险,而该风险基值是用来表示各种基因型别之间的相对风险程度高低。
本发明的用语「罹癌风险等级」是指统合了对应该目标癌症的每一种该单核苷酸多型性检测程序的该风险基值后,综合评估得出该受测者相对一般大众罹患该目标癌症的风险程度高低。
举例而言,若该目标癌症具有3种单核苷酸多型性检测程序,且检测结果的每一该风险基值分别为:中、低、低,此时可判定该受测者的该罹癌风险等级与一般大众相差不远。进一步地,该步骤S4可依据以下步骤判定该罹癌风险等级:S41.设定每一该风险基值的参考值,其中该风险基值最高者为3、最低者为1、其他为2,并取得该些风险基值的平均值。S42.若前述平均值为1,则判定该罹癌风险等级为低风险;若前述平均值大于2,则判定该罹癌风险等级为高风险;其余情况则判定该罹癌风险等级为中风险。藉由上述步骤,可使受测者更能了解自己罹患该目标癌症的可能性。
在本发明的一种实施态样中,该目标癌症为大肠直肠癌,则该单核苷酸多型性检测程序是包含有:XRCC1、NAT2、ERCC1检测程序。
XRCC1负责修复单股断裂的DNA与修复DNA上异常的碱基,在维护DNA完整性上扮演重要角色,在DNA修复的协调过程中,XRCC1能吸引相关修复酵素,而且会调节DNA的功能。若XRCC1损坏则会无法修复由活性氧、烷化物、辐射等造成的DNA损伤,而XRCC1基因变异时将导致DNA修复能力下降,因而使罹患大肠直肠癌的机率上升。
NAT2基因是芳香胺的代谢酶,也是体内重要的第二阶段代谢酶,可使活化的中间产物形成亲水性物质,而被排出体外,具有解毒作用,若NAT2基因变异导致其酶活性的降低,则解毒能力会减弱,影响人体内的新陈代谢,改变对环中毒物吸收的程度,因此NAT2活性与大肠直肠癌的发生有关。
ERCC1基因是核酸外切修复家族中重要的成员,位在第19对染色体,为重要的DNA修复基因,其编码的蛋白质与DNA连接酶Ⅲ相互作用,修复异常的核甘酸与双股断裂的DNA,并与DNA聚合酶β一起进行碱基切除修复。ERCC1基因在所有细胞中均会表现,为一高度保留的蛋白质,生活中的紫外线或化学物质皆可能造成DNA异常,若此基因发生变异,则DNA不易修复。研究亦发现,ERCC1基因多型性与大肠直肠癌的罹患机率有关。
在本发明另一种实施态样中,该目标癌症为肺癌,则该单核苷酸多型性检测程序是包含有:NAT2、CYP2D6检测程序。
NAT2是体内重要的第二阶段代谢酵素,参与许多的治疗药物、化学药物及致癌物质等代谢机能。当NAT2基因发生变异时,使得NAT2酶活性下降,造成代谢能力减缓,人体不能实时有效的将致癌物排出体外,导致过量的致癌物被人体吸收,促进肺癌形成。
CYP2D6基因为cytochromeP450(细胞色素P450酵素)超级家族中的一个成员,在肝脏组织中属第一期新陈代谢酵素,在肺癌中扮演角色为烟草、亚硝酸、尼古丁的新陈代谢活化,具有代谢药物能力及代谢环境致癌物质,毒性化合物的功能。基因多型性调控新陈代谢作用及致癌物质解毒作用,基因发生变异时,CYP2D6蛋白结构稳定度改变,亦降低与受质的结合能力,进而影响CYP2D6代谢效率。
在本发明另一种实施态样中,该目标癌症为肝癌,则该单核苷酸多型性检测程序是包含有:EGF、TNF检测程序。
表皮生长因子受体(Epidermal growth factor receptor-EGFR)为表皮生长因子家族的成员,是细胞表面受体的胞外跨膜蛋白。表皮生长因子通过与细胞表面的表皮生长因子受体(EGFR)结合,与表皮生长因子受体的高亲和力结合而过度表达及活化,激发受体内在的酪氨酸激酶的活性,从而启动了信号传递与多种生物化学变化。EGF表皮生长因子对肝细胞的生长、再生及肝脏胶原纤维的合成均有明显的刺激或抑制作用,也与肝癌发生机率有关。
TNF是一种细胞讯息传递蛋白,负责调节发炎反应,由巨噬细胞、自然杀手细胞、中性球、肥大细胞等免疫细胞分泌。肝脏细胞损伤时,为修复受损部位,肝脏内的特殊巨噬细胞-库佛氏细胞会引起发炎反应,分泌TNF-α、TGF-β、PDGF等细胞激素,活化肝星状细胞进而造成纤维化。TNF基因变异会使得TNF-α量上升,TNF-α的量越高代表着越强烈的发炎反应与组织损伤,而持续的发炎则会导致肝纤维化、肝硬化甚至是肝癌。
在本发明另一种实施态样中,该目标癌症为乳癌,则该单核苷酸多型性检测程序是包含有:BRCA1、BRCA2、HER2检测程序。
BRCA1是具有抑制恶性肿瘤发生的基因,在调节人体细胞的复制、遗传物质DNA损伤修复、细胞的正常生长方面有重要作用。其基因突变会好发乳癌、卵巢癌,会导致家族遗传性乳癌,而基因突变的患者罹患乳癌的机率为40-87%。
BRCA2基因是重要的肿瘤抑制基因,与DNA的修复、细胞周期调节及染色体结构维持有关。若BRCA2变异,DNA无法被适当地修复,则会提高家族遗传性乳癌及卵巢癌发生的风险,有报告指出BRCA2基因突变80%会造成罹患乳癌,20%造成卵巢癌。而非遗传性的偶发性乳癌及卵巢癌极少有基因突变,但有基因表达降低的现象显示基因异常也和偶发性乳癌及卵巢癌相关。
HER2为人类表皮生长因子受体,负责调控细胞的生长、分裂与修复,基因位在第17对染色体,是正常细胞中都会有的基因,但是在癌细胞中此基因会放大表现,制造过多的蛋白,导致在细胞上有过多的蛋白可以接受生长因子的刺激,使得容易生长,分裂速度快,表现出癌细胞的行为。
在本发明另一种实施态样中,该目标癌症为胃癌,则该单核苷酸多型性检测程序是包含有:PLCE1、MDM2检测程序。
PLCE1是调节细胞讯息传递的磷脂酶,可作用在磷酸肌醇产生第二传讯者,亦可与原致癌基因Ras作用,引起接续的讯息传递反应,以此影响细胞生长与基因表现;而Ras在细胞中扮演着讯息传递的功能,当异常时会使得细胞讯息传递不正常,细胞将会转形成肿瘤细胞。研究发现PLCE1在肠道肿瘤及皮肤肿瘤中扮演重要关键角色,且PLCE1的突变型与胃癌的易感性相关。
MDM2基因编码出一个核定位的E3泛素连接酶,可以通过肿瘤抑制蛋白的目标促进肿瘤的形成,为细胞内重要抑癌基因P53的负调控者,可与P53结合使其失去功能并水解。MDM2基因变异会使得基因活性增加,细胞会制造更多的MDM2蛋白,而使细胞抑癌机制受到影响。MDM2基因可经由p53就可自身转录调控,在各种不同的癌症中可检测出此基因的过量表达或是扩增。
在本发明另一种实施态样中,该目标癌症为口腔癌,则该单核苷酸多型性检测程序是包含有:MMP1、ADH1B检测程序。
基质金属蛋白酶-1(matrixmetalloproteinases-1,MMP-1)是少数可以降解Ⅰ、Ⅲ型胶原的酶,而Ⅰ、Ⅲ型胶原是构成细胞外基质的主要成分,与肿瘤细胞的侵袭有密切关系,在肿瘤的侵袭、转移、血管生成和肿瘤的发生过程中起重要作用,在口腔肿瘤中,分解口腔黏膜下结缔组织中含量最多的细胞外基质的机制,对口腔细胞癌化的进行是很重要的。
ADH1B基因所编码的蛋白质为乙醇脱氢酶(alcoholdehydrogenase1B),其作用主要为参与人体的酒精代谢途径,醇首先被ADH氧化成乙醛,其通过ALDH氧化成乙酸盐。基因变异与否影响乙醇转化为乙醛的速度,研究发现乙醛为致癌物,ADH1B变异将影响乙醛在体内的堆积量。
在本发明另一种实施态样中,该目标癌症为普遍性癌症,则该单核苷酸多型性检测程序是包含有:P53、KRAS检测程序。
P53为重要抑癌蛋白,藉由调控DNA修复、控制细胞周期与促进细胞凋亡等功能来避免癌细胞形成。当此基因产生变异,细胞调控异常,易导致癌化。
KRAS为讯息传递路径中的重要成员,调控细胞生长与代谢,主要控制细胞的增生与发展,并对癌化过程有抑制作用。当KRAS发生变异时,细胞分化及生长容易产生变异,进而造成肿瘤生长及扩散。
又,该风险基值可依以下步骤决定:S5.收集多个组经由该单核苷酸多型性检测程序取得的参考数据,该参考数据包含有多个患有该目标癌症者的基因型,以及多个未患有该目标癌症者的基因型。S6.定义多数患者的基因型为高度风险,并定义多数未患有该目标癌症者的基因型为低度风险,其余基因型为中度风险。
为方便说明,以下采用基因位点XRCC1(rs25487)的参考数据解释本发明的方法步骤。请参照图2及图3所示,每个圆点分别为每位受测者的参考数据,其中患有该目标癌症者的基因型参考数据为图2,未患有该目标癌症者的基因型参考数据则为图3。在图2及图3中,纵轴是位点为A的呈色表现,横轴是位点为G的呈色表现,其中座落在纵轴区块10a、10b的各点是纵轴(基因型为A/A)表现较高者,座落在横轴区块20a、20b的各点是横轴表现较高者(基因型为G/G),至在座落在中性区块30a、30b的各点是两轴表现平均者(基因型为A/G)。由图2可见,在20位患有大肠癌的族群中,有12人属A/A基因型,6人属A/G基因型,2人属G/G基因型,因此定义A/A基因型为罹患大肠直肠癌的高风险型。由图3可见,在21未患有大肠癌的族群中,有13人属G/G基因型,6人属A/G基因型,2人属A/A基因型,因此定义G/G基因型者为罹患大肠直肠癌的该风险基值为低风险型。
综上所述,本发明可预先评估受测者罹患何种癌症的风险较高,并依据风险等级归类,进而给予受测者生活建议或是预防性治疗,以利在癌症病发前早期予以抑制。
以上已详细说明本发明的内容,惟以上所述者,仅为本发明的较佳实施例而已,当不能以此限定本发明实施的范围,即凡依本发明申请专利范围所作的均等变化与修饰,皆应仍属本发明的专利涵盖范围内。
Claims (10)
1.一种罹癌风险评估方法,是用在评估一受测者罹患特定癌症的风险高低程度,其特征在于,该方法包含有以下步骤:
S1.取得该受测者的一检体;
S2.选定一目标癌症,该目标癌症对应多个单核苷酸多型性检测程序;
S3.依据每一该单核苷酸多型性检测程序检测该检体,并对应每一该单核苷酸多型性检测程序产生一风险基值;以及
S4.统计每一该单核苷酸多型性检测程序产生的该风险基值,并依据统计结果评估该受测者罹患对应癌症的一罹癌风险等级。
2.如权利要求1所述的罹癌风险评估方法,其特征在于,该目标癌症是选自大肠直肠癌、肺癌、肝癌、乳癌、胃癌、口腔癌或普遍性癌症其中一者。
3.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为大肠直肠癌,则该单核苷酸多型性检测程序是包含有:XRCC1、NAT2、ERCC1检测程序,
其中该XRCC1检测程序是判定该检体在基因位点XRCC1:rs25487的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:AA>AG>GG;
其中该NAT2检测程序是判定该检体在基因位点NAT2:rs1799930的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:AA=AG>GG;
其中该ERCC1检测程序是判定该检体在基因位点ERCC1:rs11615的碱基是否为C,若该位点为碱基T则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患大肠直肠癌的该风险基值呈下述关系:TT>CT>CC。
4.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为肺癌,则该单核苷酸多型性检测程序是包含有:NAT2、CYP2D6检测程序,
其中该NAT2检测程序是判定该检体在基因位点NAT2:rs1799930的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肺癌的该风险基值呈下述关系:AA=AG>GG;
其中该CYP2D6检测程序是判定该检体在基因位点CYP2D6:rs1065852的碱基是否为T,若该位点为碱基C则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肺癌的该风险基值呈下述关系:CC>CT>TT。如权利要求2项所述的罹癌风险评估方法,其中该目标癌症为肝癌,则该单核苷酸多型性检测程序是包含有:EGF、TNF检测程序,
其中该EGF检测程序是判定该检体在基因位点EGF:rs4444903的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肝癌的该风险基值呈下述关系:GG>AG>AA;
其中该TNF检测程序是判定该检体在基因位点TNF:rs1800629的碱基是否为G,若该位点为碱基A则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患肝癌的该风险基值呈下述关系:AA=AG>GG。
5.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为乳癌,则该单核苷酸多型性检测程序是包含有:BRCA1、BRCA2、HER2检测程序,
其中该BRCA1检测程序是判定该检体在基因位点BRCA1:rs16941的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>AG>AA;
其中该BRCA2检测程序是判定该检体在基因位点BRCA2:rs144848的碱基是否为T,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>GT>TT;
其中该HER2检测程序是判定该检体在基因位点HER2:rs1136201的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患乳癌的该风险基值呈下述关系:GG>AG>AA。
6.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为胃癌,则该单核苷酸多型性检测程序是包含有:PLCE1、MDM2检测程序,
其中该PLCE1:rs2274223检测程序是判定该检体在基因位点PLCE1:rs2274223的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患胃癌的该风险基值呈下述关系:GG>AG>AA;
其中该MDM2检测程序是判定该检体在基因位点MDM2:rs2279744的碱基是否为T,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患胃癌的该风险基值呈下述关系:GG>GT=TT。
7.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为口腔癌,则该单核苷酸多型性检测程序是包含有:MMP1、ADH1B检测程序,
其中该MMP1:rs1799750检测程序是判定该检体在基因位点MMP1:rs1799750的碱基是否为G,若该位点发生删除反应则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患口腔癌的该风险基值呈下述关系:-/->-/G>GG;
其中该ADH1B检测程序是判定该检体在基因位点ADH1B:rs1229984的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患口腔癌的该风险基值呈下述关系:GG>AG>AA。
8.如权利要求2所述的罹癌风险评估方法,其特征在于,该目标癌症为普遍性癌症,则该单核苷酸多型性检测程序是包含有:P53、KRAS检测程序,
其中该P53检测程序是判定该检体在基因位点P53:rs1042522的碱基是否为G,若该位点为碱基C则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患普遍性癌症的该风险基值呈下述关系:CC>CG>GG;
其中该KRAS检测程序是判定该检体在基因位点KRAS:rs2955407的碱基是否为A,若该位点为碱基G则判断发生单核苷酸多型性,且其等位基因分析结果与该受测者罹患普遍性癌症的该风险基值呈下述关系:GG=AG>AA。
9.如权利要求1所述的罹癌风险评估方法,其特征在于,该风险基值是依据以下步骤决定:
S5.收集多个组经由该单核苷酸多型性检测程序取得的参考数据,该参考数据包含有多个患有该目标癌症者的基因型,以及多个未患有该目标癌症者的基因型;以及
S6.定义多数患者的基因型为高度风险,并定义多数未患有该目标癌症者的基因型为低度风险,其余基因型为中度风险。
10.如权利要求1所述的罹癌风险评估方法,其特征在于,在该步骤S4中包含有以下步骤:
S41.设定每一该风险基值的参考值,该风险基值最高者为3、最低者为1、其他为2,并取得该些风险基值的平均值;以及
S42.若前述平均值为1,则判定该罹癌风险等级为低风险;若前述平均值大于2,则判定该罹癌风险等级为高风险;其余情况则判定该罹癌风险等级为中风险。
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CN117409978B (zh) * | 2023-12-15 | 2024-04-19 | 贵州大学 | 一种疾病预测模型构建方法、系统、装置及可读存储介质 |
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