Matenda a Li-Fraumeni, kapena LFS, ndiwo majeremusi omwe amachititsa munthu kukhala ndi khansa zosiyanasiyana. Anthu omwe ali ndi LFS nthawi zambiri amakhala ndi khansa m'mbuyomu pamoyo wawo kusiyana ndi momwe anthu ambiri amachitira. Pangakhale ngozi yaikulu ya khansa yachiwiri kapena yotsatira ku LFS.
Matendawa amadziwika koyamba m'mabanja angapo omwe amapanga khansa yambiri yosiyana, makamaka masika, msinkhu wa moyo.
Kuonjezerapo, mamembala a banja amawoneka kuti akhoza kukhala ndi khansa yambiri, yatsopano komanso yosiyana pa moyo wawo wonse. Frederick Li ndi Joseph Fraumeni, Jr, anali madokotala omwe anayamba kufotokoza za zotsatirazi mu 1969, ndipo ndi momwe LFS inatchulidwira.
N'chifukwa Chiyani Kuopsa Kwambiri kwa Khansa?
Anthu omwe ali ndi matenda a Li-Fraumeni ali ndi chiopsezo chachikulu cha khansa chifukwa adzalandira zomwe zimatchedwa germline mutation mu TP53 yofunika kwambiri.
Kusintha kwa majeremusi ndi kusintha kwa chibadwa komwe kwachitika m "mimba ya makolo ake omwe akukhudzidwa-ndiko kuti, kusinthika kumayamba kumachitika m'maselo omwe ali ndi mazira kapena ma testes omwe amachititsa dzira ndi umuna. Kusintha kwa maselo m'maselo amenewa ndi mitundu yokhayo yosinthika yomwe ingaperekedwe mwachindunji kwa ana panthawi ya pathupi pamene dzira ndi umuna zimasonkhana kuti apange zygote. Choncho, kusintha kwa majeremusi kumakhudza maselo onse m'thupi la ana atsopano; Mosiyana ndi zimenezi, kusintha kwamasinthasintha kumachitika kwinakwake pamlingo wina pokhapokha atatha kutenga mimba, kapena zambiri, mtsogolo mwake, ndipo zimakhudza maselo owerengeka a thupi.
Zomwe zimayambitsa kusintha kwa majeremusi m'mabanja omwe ali ndi LFS ndizo zomwe zimakhudza ntchito ya jini la TP53. M'dziko la kafukufuku wa khansa, jini la TP53 ndi lovuta kwambiri moti lakhala litatchedwa "wosamalira wa genome."
TP53 ndi chotupa choyambitsa jini-ndiko kuti, ndi jini lomwe limateteza selo kuchoka pa sitepe imodzi yopita ku khansa.
Pamene jinili limagwira ntchito kotero kuti silinagwire ntchito monga ilo, kapena kuti ntchito yake yachepetsedwa kwambiri, selo ikhoza kupita ku khansa, nthawi zambiri kuphatikizapo zina zamasinthidwe. Kuyesera kwa TP53 kusinthika kwa majeremusi kunayamba koyamba mu 1990 pamene mgwirizano pakati pa p53 ndi LFS unatsimikiziridwa. Kuchokera nthawi imeneyo, zamasinthika pafupifupi 250 m'thupi lonse la TP53 zakhala zikudziwika.
Kusintha kwa jini wina, hCHK2, kunayanjananso ndi LFS, komabe, tanthauzo lake silidziwika bwino. HCHK2 jini ndi chotupa choyambitsa jini chomwe chimayambitsidwa chifukwa cha kuwonongeka kwa DNA. Mabanja ang'onoang'ono okha ndiwo amanyamula kusintha kumeneku, ndipo okhudzidwawo ali ndi ziwanda zofanana ndizo zomwe zimakhala ndi kusintha kwa TP53.
Kodi Kuopsa Kwakukulu N'kotani?
Akuti anthu ambiri omwe ali ndi LFS ali ndi mwayi wokhala ndi khansa ali ndi zaka makumi asanu ndi makumi asanu ndi anayi (40) ndipo ali ndi zaka 90 peresenti yokhala ndi zaka 60. Ngati muli ndi LFS, kaya ndinu mwamuna kapena wamkazi, ndi akazi ambiri amakhala ndi chiopsezo chachikulu kuposa amuna.
Ngati mukuyang'ana pa ngozi ya moyo wa khansa kwa amuna ndi akazi omwe ali ndi LFS ali ndi zaka 50, ndiye kuti chiopsezo chokhala ndi khansa chimawonongeka motere: 93 peresenti ya amayi ndi 68 peresenti ya amuna.
Ngati iwo ali ndi khansa, amayi amayamba kukhala ndi khansa ali ndi zaka zakubadwa: zaka 29, pa avareji, poyerekezera ndi zaka 40 amuna.
Amayi ambiri omwe ali ndi chiopsezo chapamwamba makamaka chifukwa cha khansa ya m'mawere oyambirira, malinga ndi zomwe amayi ndi anzawo adaphunzira. Ofufuzawa adapeza kuti, pakati pa akazi omwe adayesa kusintha kwa kusintha kwa TP53, khansa ya m'mawere inali yofala kwambiri. Chiwerengero cha khansa ya pachifuwa cha m'mawere chinali pafupifupi 85 peresenti ali ndi zaka 60. Phunziro lomwelo, vuto la khansa ya m'mawere linakula kwambiri pazaka za 20, zomwe zimatsimikizira kuti kuyang'anira khansa ya m'mawere kuyambira zaka 20 ndizochita zabwino kwa amayi omwe ali ndi LFS.
Mkhalidwe uwu wa chiopsezo cha kusintha kwa TP53 ndi wofanana ndi zomwe zimawonedwa mwazimayi omwe ali ndi mitsempha ya germine ku BRCA1 ndi BRCA2-majini ameneŵa adakula kwambiri ndi mbiri yodziwika za kuyesa kwa majeremusi a kusintha kwa BRCA1 / 2 ndi zozizwitsa zodziletsa (ndi otchuka monga Angelina Jolie).
Kodi Khansa Zachikulu Zimakhudza Chiyani?
Khansara iliyonse ikhoza kukhala ndi munthu aliyense pa nthawi iliyonse. Komabe, anthu omwe ali ndi LFS amadziwika kuti ali ndi matenda opatsirana khansa komanso nthawi yayitali ya mitundu yosiyanasiyana ya khansa, kuphatikizapo zotsatirazi:
- Mtundu wa osteosarcoma -mtundu wochuluka kwambiri wa khansa imene imayamba m'mafupa
- Mitsempha yofewa -mtundu wa khansara umene umayamba kuchokera m'magulu ena, monga mafuta, minofu, mitsempha, matenda a mitsempha, mitsempha ya mitsempha, kapena zida zakuya za khungu
- Khansara ya m'mawere oyambirira
- Matenda a ubongo
- Khansa ya m'magazi -khansa ya maselo opanga magazi
- Adrenal cortical carcinoma -khansa ya adrenal cortex, yomwe ili kunja kwa ma glands adrenal. Matenda a adrenal amapezeka pamwamba pa impso ndikuthandizira kugwira ntchito zosiyanasiyana.
Mu kafukufuku wa 1997 wa Kleihues, sarcoma yodziŵika bwino ku LFS inali osteosarcoma, yofanana ndi 12.6 peresenti ya milandu, yotsatiridwa ndi zotupa za ubongo (12 peresenti) ndi ziphuphu zofewa (11.6 peresenti). Pa mitsempha yofewa, ma rhabdomyosarcomas (RMS) ndiwo omwe amadziwika kawirikawiri. Zina zochepa zomwe zimatchulidwa nthawi zambiri zimakhala ndi fibrosarcomas (zomwe sizinaganizidwe kukhala zenizeni), zinyama zotchedwa fibroxanthomas, leiomyosarcomas, liposarcomas orbital, sircomas cell, ndi ma sarcomas osagwirizana. Matenda a m'magazi, kapena khansa ya magazi (monga acute lymphoblastic leukemia ndi Hodgkin's lymphoma) ndi ma carcinomas adrenocortical anachitika pafupipafupi a 4.2 ndi 3.6 peresenti.
Monga momwe mabanja ambiri okhala ndi kusintha kwa majini omwe amapezeka a LFS adziwa, ambiri mwa khansa aphatikizidwa.
Khansara ya LFS yakula kwambiri monga khansa ya khansa, mapapo, m'mimba, chithokomiro, mazira, ndi khansa zina.
Malingana ndi kuunika kwa chikhalidwe, chiopsezo chotenga sarcoma ndi ubongo wa ubongo chimawoneka kuti ndi chachikulu kwambiri pa ubwana, pomwe chiopsezo cha osteosarcoma chikhoza kukhala chapamwamba pa nthawi ya unyamata, ndipo chiopsezo cha khansa ya m'mimba ya amayi imakula kwambiri pakadutsa zaka makumi awiri ndi makumi awiri wachikulire. Ziwerengero izi ziyenera kusintha, komabe, chifukwa zizoloŵezi za kuyesedwa kwa majeremusi opangira khansa akhala akusintha.
Kodi Li-Fraumeni Syndrome Limatanthauza Chiyani?
Pali zifukwa zosiyanasiyana ndi matanthauzo a matendawa. Ena ndi ophatikizapo ena. Classic LFS ndiyo ndondomeko yowonjezera, chifukwa imafuna sarcoma diagnosis pamaso pa zaka 45, pamene zizindikiro pambuyo monga Chompret zoyesayesa anayesa kupititsa patsogolo asayansi zokhudzana ndi zotupa mitundu ndi zaka zakubadwa.
Zotsatira za Classic LFS:
- Mukupezeka kuti muli ndi sarcoma (mtundu wa khansara womwe umaphatikizapo maselo a minofu / mafupa / ziwalo / mafuta ochokera pachiyambi) asanafike zaka 45
- Mbale wachiwiri woyamba (kholo, mbale kapena mwana) ali ndi khansara iliyonse yomwe imapezeka asanafike zaka 45
- Chibale china choyamba kapena chachiwiri (chikuphatikizapo azakhali, amalume, ndi zina) ndi khansara iliyonse yomwe imapezeka asanafike zaka 45 kapena sarcoma yomwe imapezeka pa msinkhu uliwonse.
Zolemba za Li-Fraumeni-like (LFL):
- Makhalidwe a LFL amapanga ukonde wochulukirapo kuphatikizapo mitundu ina ya khansa ndikuphatikizapo achibale ena omwe ali ndi zaka 45, ndipo pali matanthauzo awiri omwe akugwiritsidwa ntchito:
- Kutanthauzira kwa mbalame: Mukupezeka ndi khansara iliyonse ya ubwana kapena sarcoma, chotupa cha ubongo, kapena kansa yapamwamba yomwe imapezeka musanakwanitse zaka makumi asanu ndi limodzi (45) ndi wachibale woyamba kapena wachiwiri-digiri ndi khansa ya Li-Fraumeni (sarcoma, khansa ya m'mawere, chifuwa cha ubongo, zosakanizika carcinoma, kapena khansa ya m'magazi) pa msinkhu uliwonse ndi wachibale woyamba kapena wachiwiri-digiri ndi khansara iliyonse pasanafike zaka 60.
- Mafotokozedwe a Eels: Muli ndi achibale awiri oyambirira kapena achiwiri omwe ali ndi malungo a Li-Fraumeni (sarcoma, khansa ya m'mawere, chifuwa cha ubongo, khansa ya m'magazi, khansa yapamwamba, khansa ya khansa ya prostate, kansa ya pancreatic) pa msinkhu uliwonse.
Choyimitsa choyimitsa:
- Muli ndi chotupa cha mitsempha ya Li-Fraumeni (sarcoma, osteosarcoma, khansa ya m'mawere ya premenopausal, chifuwa cha ubongo, kansa ya ammapapo ya khansa) isanakwane zaka 46 ndi chimodzi choyamba kapena chachiwiri- digiri yokhala ndi chotupa cha Li-Fraumeni (kupatula khansa ya m'mawere, ngati muli ndi khansara ya m'mawere) musanafike zaka zisanu ndi ziwiri kapena muli ndi zotupa zambiri kapena
- Muli ndi zotupa zambiri (kupatulapo zotupa zambiri za m'mawere), 2 zomwe zimapezeka ku mimba ya Li-Fraumeni ndipo yoyamba idachitike zaka zoposa 46 kapena
- Mukupezeka kuti muli ndi khansa ya adrenocortical kapena choroid plexus, mosasamala za mbiri ya banja.
Malinga ndi kafukufuku wa LFS ndi Schneider ndi anzake, pafupifupi 70 peresenti ya anthu omwe amapezeka kuti ali ndi matenda (kutanthauza, kutanthauzira mawu monga pamwambapa) ali ndi vuto lothandizira kusintha kwa majeremusi m'thupi la TP53.
Kusamalira Khansa
Ngati munthu ali ndi khansa, mankhwala opatsirana khansa amatha kuperekedwa, kupatulapo khansa ya m'mawere, yomwe imayambitsa matenda osokoneza bongo, osati kuti ikhale ndi lumpectomy, pofuna kuchepetsa ngozi za khansa yachiwiri ya m'mawere komanso kupeŵa mankhwala a radiation.
Anthu omwe ali ndi LFS akulangizidwa kuti asatenge mankhwala omwe amawathandiza kuti asamawononge ma ARV. Komabe, pamene ma radiation amaonedwa kuti ndi ofunika kwambiri kuti apulumutsidwe ndi matenda ena, angagwiritsidwe ntchito pa luntha la dokotala ndi wodwalayo.
Kuwunika ndi kuyang'anitsitsa
Pakhala kuyitana kwakukulu kwa akatswiri kupanga mgwirizano wokhudzana ndi momwe mabanja omwe ali ndi FLS ayenera kuwonedwera ndi kusamalidwa. Tsoka ilo, pamene sayansi ikupita mofulumira, palibe mgwirizanowu woterewu ulipo m'madera onse.
Nthawi zambiri kusintha kwa TP53 kwa anthu ambiri sikudziwika, ndipo maulendo enieni a FLS sadziwika. Chiwerengero chikusiyana pakati pa 1 pa 5,000 ndi 1 mwa 20,000. Momwe mabanja ambiri akuyesera kuyesa TP53, kufalikira kwenikweni kwa LFS kungakhale koonekera.
Kuthetsa ngozi ya khansa ya m'mawere
Ku United States, malangizo a National Comprehensive Cancer Network (NCCN) amalimbikitsa mawere a MRI kwa zaka makumi awiri ndi makumi awiri ndi makumi asanu ndi awiri mphambu zisanu ndi ziwiri (20) ndi MRI pachaka ndi mammography kuyambira zaka 30 mpaka 75. Ku Australia, malangizo amtunduwu amavomereza kuti mliriwu uyenera kuperekedwa, mwinamwake chaka chilichonse MRI imavomerezedwa kuyambira zaka 20 mpaka 50. Schon ndi anzake akulangiza kuti njira yothetsera chiopsezo chochepetsera chiwerengero cha amayi kapena chifuwa cha m'mawere chiyenera kuganiziridwa mwa amayi omwe alibe khansa ndi kusintha kwa jini la TP53 .
Zotsatira za NCCN
Malinga ndi zomwe apeza kuti chiopsezo cha khansa ya m'mawere chikuwonjezeka kwambiri pambuyo pa zaka khumi zapitazi, ndondomeko zakhala zikuphatikizira kuti kugonana kwapakati pa zaka makumi awiri ndi makumi awiri kudzapitirira zaka makumi anayi mpaka makumi asanu ndi awiri mphambu zisanu ndi zisanu ndi zisanu (40) ndiyeno kuchepa, osapindula kwambiri kwa amayi oposa zaka 60.
- Kudziwitsa abambo, kuyambira pa zaka khumi ndi zisanu ndi zitatu (18), ndikukhala ndi nthawi yeniyeni, yodzidzimitsa yokha.
- Kuchepetsa matenda a m'mawere, pamwezi 6-12, kuyambira pa zaka 20
- Zaka 20-29 zaka, chaka cha m'ma MRI kuyang'ana mosiyana
- Zaka 30-75 Zaka, chaka cha m'ma MRI kuyang'anitsitsa ndi zosiyana ndi mammogram ndi kuganizira za Tomosynthesis
- Zaka> zaka 75, utsogoleri uyenera kuganiziridwa payekha.
- Kwa amayi omwe ali ndi kusintha kwa TP53 omwe amachizidwa khansa ya m'mawere, ndipo omwe sanayambe kugonana, amaonetsetsa kuti ali ndi bere la pachaka la MRI ndipo mamemografia ayenera kupitilira monga tafotokozera pamwambapa.
- Ngati njira yothetsera chiopsezo cha mastectomy ikufotokozedwa, payenera kukhala uphungu wokhudzana ndi chitetezo, kukula kwa matenda a khansa, zaka zomangamanga, komanso zoopsa za khansa zina. Maganizo, chikhalidwe, ndi khalidwe la moyo zomwe zimachitika pochepetsa chiopsezo chotenga kachilombo ka HIV zimayenera kuphatikizidwa mu zokambirana.
Kulimbana ndi Vuto Lina la Khansa
Zotsatira za NCCN
- Kuyezetsa thupi kwakukulu kuphatikizapo kufufuza kwa ubongo ndi chiwerengero chokwanira cha khansa yosawerengeka ndi zizindikiro zachiwiri za opulumuka khansara iliyonse miyezi 6-12.
- Colonoscopy ndi chapamwamba kumapeto kwa zaka 2-5 kuyambira pa zaka 25 kapena zaka zisanu isanafike khansa yoyamba yamtunduwu yamtundu wa banja (chomwe chimabwera poyamba).
- Kufufuza kwa chaka ndi chaka kuyambira zaka 18.
- Thupi lonse la pachaka MRI
- Ubongo wamakono MRI ikhoza kuchitidwa ngati gawo la thupi lonse la MRI kapena ngati kupenda kosiyana.
Mafomu Ena A Kuwunika ndi Kuyang'anitsitsa
Panali woyesa woyendetsa pilot wa positron emission tomography (FDG-PET) / CT akuyang'ana akuluakulu omwe ali ndi LFS omwe anawona zotupa mwa atatu mwa anthu 15. Izi zimapangitsa kuti PET-CT iziwone, ngakhale kuti zikhoza kupeza zithupsa zina, zimapangitsa kuti dzuwa liziwoneka bwino.
Magulu angapo ochita kafukufuku ayamba kugwiritsa ntchito pulojekiti yowonongeka kwambiri kuphatikizapo MRI, thupi lonse, MRI ubongo, kuyang'ana kwa ultrasound m'mimba, ndi kuyesa ma labata a adrenal cortical ntchito. Ndondomeko yotereyi ikhoza kupulumutsa anthu omwe ali ndi LFS pozindikira zivomezi zisanakhale zizindikiro, koma maphunziro ambiri amafunika kuti asonyeze kuti mtundu uwu wa boma ukugwira ntchito kwa akuluakulu ndi ana omwe ali ndi LFS.
Anthu omwe ali ndi LFS akhala akufunsidwa za momwe amaonera kansalu, ndipo ambiri amakhulupirira kufunika kwa kuyang'anitsitsa kuti awone zotupa kumayambiriro. Ananenanso kuti kukhala ndi chitetezo ndi chitetezo kumagwirizana ndi kutenga nawo mbali pa pulogalamu yowonongeka
Kuyesera Ana kwa kusintha kwa TP53
N'zotheka kuyesa ana ndi achinyamata kuti asinthe kusintha kwa LFS, komabe nkhaŵa zakhala zikukhudzidwa potsata zowopsa, zopindulitsa, ndi zoperewera zomwe zimachitika, kuphatikizapo kusowa njira zowonetsera kapena njira zothandizira, komanso nkhawa za kusalidwa ndi kusankhana.
Zilimbikitsidwa kuti ayese achinyamata omwe ali ndi zaka zoposa 18 kuti mitundu yosiyanasiyana ya TP53 ichitike mkati mwa pulojekiti yomwe imapereka mauthenga onse omwe asanatengedwenso komanso apambuyo poyesa.
> Zotsatira:
> Ballinger ML, Best A, Mai PL, et al. Kuyang'anitsitsa kwapadera ku Li-Fraumeni syndrome pogwiritsa ntchito kujambula kwathunthu kwa maginito: Chithunzi cha meta [chofalitsidwa pa intaneti pa August 3, 2017]. JAMA Oncol.
> Correa H. Li-Fraumeni Syndrome. J Wodwala Genet. 2016; 5 (2): 84-88.
> Katherine Schon ndi Marc Tischkowitz. Kachilombo ka HIV kumakhudza kusintha kwa germine mu khansa ya m'mawere: TP53. Matenda a khansa ya m'mawere. 2018; 167 (2): 417-423.
> Mai PL, AF Wabwino, Peters JA, et al. Mavuto a khansa yoyamba ndi yotsatira pakati pa TP53 osokoneza mutundu mu gulu la NCI LFS. Khansa . 2016; 122 (23): 3673-3681.
> NCCN malangizo othandizira odwala pogwiritsa ntchito njira zowonjezereka 1.2018 - October 3, 2017: Kuyezetsa magazi kwa amayi ndi abambo: mawere ndi mazira. Malangizo a NCCN Otsogolera Othandizira: http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.
> Tinat J, Bougeard G, Baert-Desurmont S, et al. Matenda a Chompret a 2009 a Li Fraumeni . J Clin Oncol. 2009; 27 (26): e108-9.