GENETYKA W ONKOLOGII ASPEKTY MEDYCZNE I EKONOMICZNE J
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GENETYKA W ONKOLOGII – ASPEKTY MEDYCZNE I EKONOMICZNE J. Lubiński INTERNATIONAL HEREDITARY CANCER CENTER POMERANIAN MEDICAL UNIVERSITY READGENE SA Warszawa 25. 10. 2011 r.
F If we want to solve problem / be successful F we need to: a) work hard and wise b) be lucky
Luck!!! Poland F ~38 mln country with high level of genetic homogeneity
Górski B. et al. AJHG, June 2000
POLISH FAMILIES WITH STRONG AGGREGATION OF BREAST/OVARIAN CANCERS (n=200) F BRCA 1 F BRCA 2 ~65% ~4% Górski B. et al. Int. J. Can, 2004
POLISH PANEL OF BRCA 1 MUTATIONS F 5382 ins C F C 61 G F 4153 del A 90% of mutations Górski B. et al. Int. J. Can, 2004
BRCA 1 FOUNDER MUTATIONS IN POLAND F GÓRSKI B. ET AL. - PATENT NO P 335917 - MULTIPLEX PCR - 50€
A. BRCA 1 PROPHYLACTICS F Oral contraceptives < 30 yrs > 30 yrs F Breast feeding > 1 yrs F Later menarche per yr F Tubal ligation 0. 5 F Adnexectomy F Tamoxifen F Adnexectomy + tamoxifen RISK BR OV 1. 3 0. 5 0. 9 0. 2 0. 5 0. 15 0. 05
Scientific background DETECTION OF EARLY BREAST CANCERS IN BRCA 1 MUTATION CARRIERS USG ~20% MAMMOGR. ~20% MRI ~90% Narod S. et al. 2003
DIFFERENCES IN TREATMENT OF BRCA 1 BREAST CANCERS F Prophylactic adnexectomy F Tamoxifen F Chemotherapy
MSH 2 / MLH 1 tests F In families matching the following criteria: Ø CRC + CRC END SB UR. TR. Ø ≥ 1 of cancers DGN < 50 yrs
FEATURES MODIFYING RISK OF COLORECTAL CANCER IN CARRIERS OF MSH 2/MLH 1 MUTATION BEGINING F COLOSCOPY WITH POLYPECTOMY 25 YRS F INTRAVAGINAL USG 35 YRS F RISK FROM 80% TO 30% F DETECTION OF EARLY CANCERS EVERY 2 YRS 1 YRS
POPULATION SCREENINGS IN POLAND F 4% (~200) of BRCA 1 carriers among 5000 relatives of women with breast cancer dgn < 50 yrs or ovarian cancer dgn at any age F Thanks to geneticists - oncologists from 20 Polish centers!
POPULATION SCREENINGS IN POLAND WEST-POMERANIA REGION JANUARY 2001 – MAY 2002 F 1, 258 mln questionaires out of 1, 45 mln of inhabitants F the first worldwide large screening for hereditary cancers
POPULATION SCREENINGS IN POLAND BRCA 1 F MUTATION DETECTION COST F SURVEILLANCE COST 1650 € (USG, MAMMOGRAPHY, FNAB, ADNEXECTOMY, TAMOXIFEN) F RISK REDUCTION Ø BREAST 60% 10% (WITHOUT PROPHYLACTIC MASTECTOMY) 750 €
COMPELLING ECONOMICS OF PREVENTION F Treatment costs 2000 -2003 BRCA 1 mutation carriers 500 € with~5 breast/ovarian cancers N=50 F Social security costs ~8 800 € F GP per capita lost ~50 000 € ~64 300 € Marska N, US 2004
High penetrance/risk – breast ca F Family history F DNA tests ü BRCA 1 ü BRCA 2 ü CHEK 2 – homozygotes – htr + FH – BRCA 2 (5972 C/T) ü ATM
NATIONAL PROGRAMME URGENTLY NEEDED!!!
Milestone discoveries 2. Complete remission of BRCA 1 – dependant breast cancers using Cis-platinum International Hereditary Cancer Center 2008/9
BRCA 1 -dependendnt breast cancer Preoperative treatment F 44 patients F 15 (+) – 10/15 p. CR – 67% F 29 (−) – 24/29 p. CR – 83%
Retrospective analysis neoadjuvant treatment of 141 consecutive BRCA 1 mutation carriers with diagnosis of breast cancer < 51 yrs (n=7000)
CHEMOTHERAPY F Neo-adjuvant treatment of breast cancer – complete pathologic remission F > 95% of five year survival !
BRCA 1 – dependent BC F METASTATIC STUDY
Response to treatment Months since initiation of treatment, * mean Number deceased Response Number Evidence of progression Complete 9 6 29. 3 2 Partial 7 4 27. 6 5 Stable disease 3 3 13. 6 3 Progressive 1 1 6. 0 1 From date of first treatment untill July 31, 2011 if alive, or untill date of death, if dead Byrski T et al.
CONCLUSIONS 1. Platinum-based chemotherapy is effective in a high proportion of patients with BRCA 1 -associated breast cancers 2. BRCA 1 testing is a critical issue for choice of breast cancer treatment 3. Validating studies needed
Milestone discoveries F Cancer chemoprevention using selenium International Hereditary Cancer Center 2011
Przyczyny dotychczasowych niepowodzeń F Stężenia Se w diecie / organizmie? F Osobnicze różnice w genotypach?
Asocjacja pomiędzy poziomem Se we krwi a ryzykiem raków piersi zależnie od genotypów a) Kolejne raki piersi b) Raki piersi u nosicielek mutacji BRCA 1
Asocjacja pomiędzy poziomem Se we krwi a ryzykiem raków piersi zależnie od genotypów
Asocjacja pomiędzy poziomem Se we krwi a ryzykiem raków piersi zależnie od genotypów
Asocjacja pomiędzy poziomem Se we krwi a ryzykiem raków płuca i krtani niezależnie od genotypów
Rak płuca F I vs IV ćwiartka p<0. 0001 OR 13. 2 CI 4. 6 -37. 6 F Se<56 μg/l 34/42 Se>90 -110 μg/l 0/15 !!! p<0. 0001 OR 125. 8
Ryzyko raka płuca a stężenie selenu we krwi Ryzyko 6 5 4 3 2 1 0 0 20 40 60 80 Polska 100 120 140 USA 160 180 200 stężenie Se [μg/l]
Wniosek – podsumowanie F Poziom selenu markerem grup ryzyka raków tytoniozależnych np. kwalifikacja do TK płuc? F optymalizacja poziomu selenu – kilkakrotne obniżenie ryzyka raków tytoniozależnych?
Wniosek – podsumowanie F Genetyka w onkologii – wielki innowacyjny potencjał do wdrożenia zwłaszcza w POLSCE
COMMERCIALISATION ECONOMICAL APPLIED READ GENE RESEARCH CRISIS SA – SPIN OFFS
READ GENE SA Main task: global leadership in cancer chemoprevention
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