I-Li-Fraumeni syndrome, okanye i-LFS, imeko yezofuzo ebangela ukuba abantu bahluke kwiindlela ezahlukeneyo zeentsholongwane. Abantu abaneLFS bavame ukuhlakulela la makhansela ngaphambili ebomini kunokuba kubonakala ngokubanzi kuluntu. Kukho nokuba kubekho mngcipheko omkhulu wegciwane lesibini okanye elilandelayo kwiLFS.
I-syndrome yabonwa kuqala kwiintsapho ezininzi ezahlukahlukeneyo ezahlukeneyo ezinomdlavuza, ngokukhethekileyo iiscarcas, ebusweni bokuqala.
Ukongezelela, amalungu omndeni avela ukuba akwazi ukuvelisa umdlavuza omtsha, omtsha kunye nohlukileyo kwixesha lokuphila. UFrederick Li noJoseph Fraumeni, Jr, babengabagqirha abaqala ukuxela ngalezi ziphumo ngo-1969, kwaye yiloo ndlela uLFS enegama layo.
Kutheni i-Higher Risk of Cancers?
Abantu abane-Li-Fraumeni syndrome banomngcipheko ophezulu womhlaza ngenxa yokuba bazuze into eyaziwa ngokuba yintsholongwane yegciwane kwi-gene ebizwa ngokuba yi-TP53.
Ukutshintshwa kwintsholongwane yintsholongwane yintshintsho yezofuzo ezenzeke kwi-germ line yabazali abachaphazelekayo-oko kukuthi, ukutshintshwa kwangoko kuvela kwiiseli kumaqanda okanye kwiimvavanyo ezivelisa iqanda kunye nesidoda. Izinguqulelo kulezi zisele ziphela kuphela iintlobo zenguqu ezinokutshintshwa ngqo kwinzala ngexesha lokukhulelwa xa iqanda nediza zihlangana ukuze zenze i-zygote. Ngaloo ndlela, ukuguqulwa kwamagciwane kuya kutshintshela zonke iiselingi emzimbeni wenzala entsha; Ngokwahlukileyo, ukuguqulwa kwamathambo kuphuhliso kwindawo ethile kwindawo ethile emva kokukhulelwa, okanye ezininzi, emva koko, kwaye zichaphazela inombolo eguqukayo yamaseli emzimbeni.
Iinguqu eziphambili zentsholongwane kwiintsapho kunye ne-LFS yizo ezichaphazela umsebenzi wegciwane le-TP53. Ehlabathini lephando lomhlaza, i-TP53 yegeni ibaluleke kangangokuba ibizwa ngokuba "ngumgcini we-genome."
I-TP53 yimizimba ye-tumor-suppressor gene-oko kukuthi, ngumzimba okhusela iseli ukusuka kwelinye inyathelo endleleni eya kumhlaza.
Xa lo mfuzo uguquka kangangokuba awusebenzi njengoko kuhloswe, okanye ukuba umsebenzi wayo uncitshiswe kakhulu, iseli ingaqhubela phambili kumhlaza, kaninzi udibaniswa nezinye iinguqu zofuzo. Ukuvavanywa kwe- TP53 yintsholongwane yentsholongwane yaqala ngo-1990 xa ikhonkco phakathi kwe-p53 ne-LFS yaqinisekiswa. Ukususela ngoko, ukuguqulwa kwamalunga nama-250 kuwo wonke umthamo we- TP53 kuye kwafunyanwa.
Ukuguqulwa komnye umfuzo, hCHK2, kwaye kwahlanganiswa ne-LFS, nangona kunjalo, ukubaluleka kwayo akucaci. I-gene hCHK2 i-genetic suppressor gene eyenziwa ngokuphendula umonakalo we-DNA. Inani elincinci leentsapho lithwala lolu tshintsho, kwaye abo bachaphazelekayo banamanani afana neentlondi ezifana nezo ziguquko ze-TP53.
Ingozi ephezulu kangakanani?
Kuqikelelwa ukuba, ngokubanzi, umntu ophethe i-LFS unamathuba e-50 ekhulwini lokuba nomhlaza ngeminyaka engama-40 kunye namaxesha angama 90 engama-60 ubudala. Ukuba unayo i-LFS, umngcipheko wakho ngamnye uxhomekeke kwicandelo enoba ungowesilisa okanye ngowesifazana, kunye namabhinqa ayenomngcipheko ophezulu kunabesilisa.
Ukuba ubheka ingozi yokuphila komhlaza kumadoda kunye nabasetyhini abane-LFS kwiminyaka engama-50 ubudala, umngcipheko wokuba nomhlaza uphula phantsi ngale ndlela: iipesenti ezingama-93 kubafazi kunye nama-68 ekhulwini ngamadoda.
Ukuba bahlakulela umhlaza, abafazi nabo bavame ukuphuhlisa umhlaza kwiminyaka yobudala: iminyaka engama-29, ngokwesilinganiso, ngokumalunga neminyaka engama-40 ubudala emadodeni.
Umngcipheko ophezulu kumabhinqa ngokuyinhloko ngenxa yomdlavuza webele webele, ngokutsho kwesifundo seMai kunye noogxa. Aba baphandi baphinde bafumanisa ukuba, phakathi kwabasetyhini abavavanywe kakuhle kwiintshukumo ze-TP53, umdlavuza webele wawungowona udlala kakhulu. Isiganeko somhlaza wesifuba esibambileyo sasingama-85 ekhulwini ngaminyaka engama-60. Kwisifundo esifanayo, ingozi yomhlaza wesikhumba yanda kakhulu ngexesha le-20s yomfazi, eqinisekisa ukuba ukuhlolwa komhlaza wesifuba ukususela kwiminyaka engama-20 ubudala kuyinto efanelekileyo kubafazi abane-LFS.
Eli nqanaba lomngcipheko wokutshintshwa kwe-TP53 lithelekiswa nento ebonwa ngabasetyhini abaneentsholongwane zentsholongwane kwi-BRCA1 kunye ne-BRCA2-ezi zigulo ziphakanyisiwe kunye neengxelo ezidumileyo malunga nokuhlolwa kofuzo lwe-BRCA1 / 2 kunye nokuguqulwa kwamathambo (kubanjwe njengo-Angelina Jolie).
Ziziphi iiCatal Cancer ezibandakanyekayo?
Nayiphi na umhlaza unokuhlakulela kumntu nawuphi na ixesha. Nangona kunjalo, abantu abane-LFS bayaziwa ukuba banokuxilongwa komhlaza wokuqala kunye nomngcipheko ophezulu wobomi bezinto ezininzi "eziphambili" zomhlaza, kubandakanywa oku kulandelayo:
- I-Osteosarcoma- uhlobo oluqhelekileyo lomhlaza oqala emathanjeni
- Ama-sarcomas-ahlukileyo- uhlobo lomdlavuza ovela kwizicubu ezithile, njengamafutha, isisipha, ama-nerf, ama-tissu ama-fibrous, imithwalo yegazi
- Umhlaza wesifuba sokuqala
- Izibilini zesibindi
- I-leukemia- ngumhlaza weeseli ezenza igazi
- I-Adrenal cortical carcinoma- umhlaza we-correnx ye-adrenal, oyingqimba lwangaphandle lweengqungquthela ze-adrenal. Izilonda ze-adrenal ziphezu kweentso kwaye zidlala indima ebalulekileyo kwimisebenzi eyahlukeneyo ye-hormonal.
Ngophando luka-1997 lwe-Kleihues, i-sarcoma eyaziwa ngokuqhelekileyo kwi-LFS yayingu-osteosarcoma, ehambelana nama-12,6 ekhulwini lamatyala, alandelwa ngamathumbu eengqondo (iipesenti ezili-12) kunye neengqungquthela eziphathekayo (11.6 pesenti). Kwiisarumas ezifudumele, i-rhabdomyosarcomas (i-RMS) yizona ziqhelekileyo zichongwe. Ezinye iisargas eziqhelekanga ezingabonakali zibandakanya i-fibrosarcomas (engasayi kuthathwa njengeyinyaniso eyinyani), i-fibroxanthomas ye-atypical, i-leiomyosarcomas, i-libiarpas okanye i-liposarcomas, i-sarcomas okanye i-sarcomas engaxhamliyo. Izifo ze-Hematological, okanye i-blood cancer (ezifana ne-acute lymphoblastic leukemia kunye neHodgkin's lymphoma) kunye ne-carcinomas e-adrenocortical yenzeka kwi-4.2 kunye ne-3.6 ekhulwini, ngokulandelana.
Njengoko ezinye iindwendwe ezinokuguqulwa kwemfuyo efana ne-LFS sele zichongiwe, ezininzi i-cancer ziye zafakwa.
I-spectrum yomdlavuza we-LFS iye yanda ukuba iqulethe i-melanoma, imiphunga, isisu somzimba, i-thyroid, i-ovarian kunye nezinye i-cancer.
Ngokusekelwe kovavanyo lwemveli, umngcipheko wokuphucula i-sarcoma yesisu kunye nomhlaza wengqondo kubonakala kubaluleke kakhulu ebuntwaneni, ngelixa ingozi ye-osteosarcoma ingaba phezulu kwi-adolescence, kwaye umngcipheko wesifo somhlaza wesibindi wesifazane unyuke kakhulu malunga no-20 ubudala kwaye uqhubeka udala badala. Ezi zibalo zinokutshintshwa, nangona kunjalo, ekubeni izenzo zokuvavanya i-gene-predisposition genes ziye zaguquka.
Li-Fraumeni Syndrome ichazwa njani?
Kukho iinkqubo ezahlukeneyo kunye neenkcazo zesi sifo. Ezinye zibandakanya ngakumbi kunabanye. I-LFS yeClassic iyona nto inqabileyo kakhulu, njengoko idinga ukuxilongwa kwe-sarcoma ngaphambi kweminyaka engama-45, ngelixa iinguqu ezilandelayo ezifana ne-criteria ye-Chompret zizama ukuphinda ziguqule ulwazi lwezesayensi malunga neentlobo zee-tumor kunye namaxesha angama-diagnostic.
Imigaqo yeLFS yeClassic:
- Ufunyaniswa ukuba une-sarcoma (uhlobo lomhlaza olubandakanya amaseli e-muscle / i-skeletal / amalunga / imvelaphi yeoli) ngaphambi kweminyaka engama-45 kwaye
- Isihlobo esithile sokuqala (umzali, umntakwabo okanye umntwana) nayiphi na umhlaza ofunyanwe phambi kweminyaka engama-45 kwaye
- Esinye isihlobo sokuqala okanye sesibini (kubandakanya oomama, oomama, kunye nokunye) nangomphi umhlaza ofunyanwe phambi kweminyaka engama-45 okanye i-sarcoma efunyanwe nanini na.
Imilinganiselo yeLi-Fraumeni-like (LFL):
- Imilinganiselo ye-LFL ifake inetha elibanzi ukuquka ezinye iintlobo zomhlaza kwaye zibandakanye ezinye izalamane ezixilongwe emva kweminyaka engama-45, kwaye kukho izichaso ezimbini ezahlukeneyo ezisetyenziswayo:
- Inkcazo ye-Birch: Ufunyenwe ukuba unomdlavuza okanye umntwana, okanye i-sarcoma, i-tumor ye-brain, okanye i-carcinoma ene-adrenocortical ifunyanwe ngaphambi kweminyaka engama-45 kunye nesihlobo sokuqala okanye sesibini kwisixa somhlaza we-Li-Fraumeni (i-sarcoma, umhlaza wesifuba, isisu seengqondo, i-adrenocortical i-carcinoma, okanye i-leukemia) nawuphi na umdala kunye nesihlobo sokuqala okanye sesibini kwisihlobo nomhlaza ngaphambi kweminyaka engama-60 ubudala.
- I-Eels inkcazo: Unesihlobo sokuqala sesibili okanye sesibini kwisibeleko se-Li-Fraumeni (i-sarcoma, umdlavuza webele, isifo seengqondo, i-leukemia, i-tumor, i-melanoma, umdlavuza we-prostate, umdlavuza we-pancreatic) nawuphi na umdala.
Iimpawu zokunyusa:
- Unomsila we-Li-Fraumeni i-tumor spectrum (i-sarcoma e-soft-tissue sarcoma, i-osteosarcoma, umdlavuza webele we-premenopausal, i-tumor ye-brain, i-adrenocortical carcinoma, i-leukemia, okanye umhlaza womphunga wamaphaphu) ngaphambi kweminyaka engama-46 kwaye ubuncinane omnye wokuqala okanye wesibini. isilinganisi esilumkileyo nesifo se-Li-Fraumeni (ngaphandle kwesifo somhlaza wesifuba, ukuba unomdlavuza wesibeleko) ngaphambi kweminyaka engama-56 okanye ngeesisu okanye
- Unamaxuba amaninzi (ngaphandle kwezihlamba ezininzi zesifuba), ezi-2 zazo ezise-spectrum ye-Li-Fraumeni kunye neyokuqala eyenzeka ngaphambi kweminyaka engama-46 okanye
- Ufunyanwe ukuba une-carcinoma ye-adrenocortical okanye i-choroid plexus tumor, kungakhathaliseki ukuba imbali yentsapho.
Ngokutsho kokuhlaziywa kwe-LFS nguSchneider kunye nabalingane, ubuncinane ubuncinane abangama-70 ekhulwini abantu abafunyaniswa ngonyango (oko kukuthi, ukusebenzisa izichazi ezifana nalezi ngasentla) zinokuguqulwa kokutshintshwa kwegciwane lesigxina kwi-TP53 yokunciphisa i-tumor.
Ulawulo lweKhansela
Ukuba umntu one-LFS eba nomdlavuza, unyango lwe-cancer oluqhelekileyo lukhuthazwa, ngaphandle kwe-cancer yombele, apho i-mastectomy, kunokuba i-lumpectomy, icetyiswa ukwenzela ukunciphisa ingozi yesifo somhlaza wesibini kunye nokukhusela unyango lwe-radiation.
Abo bafumana i-LFS bayacetyiswa ukuba baphephe unyango lwe-radiation nanini kunokwenzeka ukuze kunciphise umngcipheko wezonyango ezibangelwa yi-radiation. Nangona kunjalo, xa i-radiation ithathwa njengemfuneko yempilo ukuphucula ithuba lokusinda kwisifo esibi, singasetyenziselwa ukuqonda kwonyango kunye nesigulane.
UkuHlola nokuHlola
Kukho ukunyuka kokwanda kweengcali ukwenza isivumelwane malunga nendlela iintsapho ezine-FLS kufuneka zihlolwe ngayo kwaye zinakekelwe. Ngelishwa, ngelixa isayensi iguqukela ngokukhawuleza, akukho vu melwano olukhoyo kuzo zonke iindawo.
Ubuninzi bezinto ezinobungozi be- TP53 zinguqu kubantu abaqhelekileyo aziwazanga, kwaye iifayile zangempela ze-FLS aziwa. Uqikelelo luhluka phakathi kwe-1 kwi-5,000 kunye no-1 kuma-20,000. Njengoko ezinye iindwendwe zihlola uvavanyo lwe-TP53, ukunyuka kwenene kwe-LFS kunokucaca.
Ukujongana nobungozi besifo somhlaza webele
E-United States, izikhokelo ze-National Comprehensive Cancer Network (NCCN) zincoma i-MRI yaminyaka yonke iminyaka engama-20-29 kunye ne-MRI yonyaka kunye ne-mammography kwiminyaka engama-30 ukuya kwe-75. E-Australia, izikhokelo zesizwe zincoma ukuba i-mastectomy ye-bilater kufanele ihanjiswe, ngaphandle koko i-MRI yamabele yonyaka iphakanyiswa ukususela kwiminyaka engama-20 ukuya kwe-50. U-Schon kunye noogxa bakhe bancomela ukuba ukhetho lokunciphisa umngcipheko we-mastectomy okanye ukuhlolwa kwebele kulindeleke kuthathelwe ingqalelo kubasetyhini abangenawo umdlavuza onguquko kwi- gene553 .
Iziphakamiso zeNCCN
Ngokusekelwe ekufumaneni ukuba ingozi yomhlaza wesifuba yanda kakhulu emva kweyeshumi leminyaka, iingcebiso zibandakanya ukuba i-mastectomy ephakathi kwamanye amazwe kufuneka icingelwe ukususela kwiminyaka engama-20. Ingozi yomhlaza wonyaka wonyaka isondele kwiminyaka engama-40 ukuya ku-40 ukuya kweyesihlanu kwaye iyancipha, njengokuba i-mastectomy kuncinci ukuba bazuze abafazi abangaphezu kweminyaka engama-60.
- Ukwazisa ngesifuba, ukususela kwiminyaka eyi-18 ubudala, kunye nexesha, ukuzithobela isifuba esifanayo.
- Uvavanyo lwebele lwezonyango, zonke iinyanga ezi-6-12, ukuqala kwiminyaka engama-20
- Iminyaka engama-20-29 ubudala, i-breast MRI yokuhlola i-breast
- Iminyaka engama-30-75 ubudala, i-breast-breast screening ye-MRI ngokuhlukileyo kunye ne-mammogram ngokuqwalaselwa kwe-Tomosynthesis
- Umdala> iminyaka engama-75, ulawulo kufuneka luqwalaselwe ngumbandela ngamnye.
- Kwabafazi abanokuguqulwa kwe-TP53 abaphethwe ngumhlaza wesibele, kunye nabangenayo i-mastectomy, i-IRM kunye ne-mammogram kufuneka iqhubeke njengoko ichaziwe ngasentla.
- Xa kukhethwa ingqalelo kwindlela yokunciphisa umngcipheko we-mastectomy, kufuneka kube neengcebiso ngokumalunga nezinga lokukhusela, umlinganiselo wengozi emfutshane yengqondo yomhlaza, iindlela zokwakhiwa kwakhona, kunye neengozi ezikhuphisanayo nezinye i-cancer. Iinkalo zengqondo, ezentlalontle kunye nemigangatho yempilo yezinto eziphantsi kokunciphisa umngcipheko wokunciphisa umngcipheko kufuneka zifakwe kwiingxoxo ezinjalo.
Ukubhekiselele kwenye ingozi yomhlaza
Iziphakamiso zeNCCN
- Uvavanyo oluqhelekileyo lomzimba kubandakanya ukuhlolwa kwe-neurologic kunye nenqaku eliphezulu lokusola kwiidlingozi ezingabonakaliyo kunye neentsholongwane zesibini kwiintsholongwane zomhlaza nganye kwiinyanga ezi-6-12.
- I-Colonoscopy kunye ne-endoscopy ephezulu yonke iminyaka emi-5 ukuya ku-5 ukusuka kwiminyaka eyi-25 okanye kwiminyaka emi-5 ngaphambi komdlavuza wokuqala wekoloni kwintsapho (nokuba yiyiphi eya kuqala).
- Uviwo lwe-dermatologic ngonyaka oluqala kwiminyaka eyi-18.
- Umzimba wonke wonyaka weMRI
- Ingqiqo yonyaka Ingxelo ye-MRI ingenziwa njengenxalenye yomzimba wonke we-MRI okanye uvavanyo olulodwa.
Ezinye iifomu zokuHlola kunye nokuGadwa
Kwakukho ityala lokulinganisa i-positron emission tomography (FDG-PET) / i-CT izicatshulwa kubantu abadala abane-LFS abafumene izicubu kubantu abathathu kwaba-15. Ezi ziphumo ze-PET-CT, nangona zinkulu ekufumaneni izicubu ezithile, zandisa ukwanda kwemisebe rhoqo xa zenziwe, kwaye ke le ndlela yokutshekisha iyanqanyulwa kwaye yatshintshela kwi-MRI yomzimba wonke kubantu abadala nge- TP53 .
Amacandelo amphando athile sele aqalise ukusebenzisa inkqubo ebonakalisiweyo yokujonga i-IRM, i-MRI yengqondo, ukuhlolwa kwe-abdominal ultrasound, kunye neemvavanyo zebhan ze-acrenal cortical function. Lolu hlobo lwenkqubo yokulinda lunokuphucula ukuphila kwabantu abane-LFS ngokufumana izicubu phambi kokuba kukho naziphi iimpawu, kodwa kukho iimfuno ezininzi ezifunekayo ukubonisa ukuba lolu hlobo lolawulo lusebenza kubantu abadala kunye nabantwana abane-LFS.
Abantu ngabanye abane-LFS baye babuzwa malunga nesimo sengqondo sabo ngokubhekisele kumdlavuza, kwaye baninzi babonakala bekholelwa kwixabiso lokuhlola ukuba bafumane iimvumi ngexesha lokuqala. Baphinde babike ingqiqo yolawulo kunye nenqabiseko enxulumene nokuthatha inxaxheba kwinkqubo yokujonga rhoqo
Ukuvavanya abantwana kwi-TP53 utshintsho
Kunokwenzeka ukuvavanya abantwana kunye nabaselula malunga nokuguquka okuphawulekayo kwe-LFS, kodwa ukukhathazeka kuye kwaphakanyiswa malunga nobungozi, inzuzo kunye nokunciphisa kokwenza njalo, kubandakanywa ukungabikho kocando oluqinisekisiweyo okanye izicwangciso zokuthintela, kunye nokukhathazeka ngokunyaniseka nokucwaswa.
Kucetyiswa ukuba ukuvavanya abantu abangaphantsi kweminyaka engama-18 ukwenzela ukuba iinguqu ze- TP53 ze- pathogenic zenziwe kwiprogram enika kokubili ukuvavanywa kwangaphambili nokuvavanywa kolwazi kunye nokucebisa.
> Imithombo:
> I-Ballinger ML, Eyona ndlela ihamba phambili A, Mai PL, et al. Ulwalathiso olusisiseko kwi-Li-Fraumeni syndrome isebenzisa ukucamngca kwemifanekiso emzimbeni wonke: uhlalutyo lweemeta [olupapashwe kwi-intanethi ngo-Agasti 3, 2017]. JAMA Oncol.
> Correa H. Li-Fraumeni Syndrome. J Pediatr Genet. 2016; 5 (2): 84-88.
> Katherine Schon noMarc Tischkowitz. Iimpembelelo zesifo se-germline kwi-cancer yombele: TP53. Ukwelashwa kweCanscer Res Treatment. 2018; 167 (2): 417-423.
> PL PL, I-AF ephezulu, uPeter JA, et al. Ubungozi bokuqala beengqungquthela zegciwane phakathi kwe- TP53 yotshintsho-zithuthi kwiqela le-NCI LFS. Cancer . 2016; 122 (23): 3673-3681.
> I-NCCN yezikhokelo zonyango kwi-oncology 1.2018-Oktobha 3, 2017: Uvavanyo lwe-Genetic / lwentsapho oluphezulu lwengozi: ibele kunye ne-ovarian. Izikhokelo zeNCCN Clinical Practice Guidelines: http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.
> Tinat J, Bougeard G, Baert-Desurmont S, et al. Inguqulelo ka-2009 ye-Chompret imigaqo ye-Li Fraumeni syndrome . J Clin Oncol. 2009; 27 (26): e108-9.