Ghi chú: m u mô vú c a các b nh nhơn tu i nh h n 40, t 40 - 50 vƠ cao h n tu i 50 l n l t lƠ N1, N2, N3. M u môvú trong giai đo n I, II, III vƠ IV.
3.3.5. Xác đnh m i t ng quan gi a s methyl hóa gen p16INK4 vƠ b nh ung th th
K t qu ghi nh n trên m u b nh ung th vú vƠ m u mô lƠnh tính đ c x lỦ th ng kê, nh m tính toán m i t ng quan gi a t l methyl hóa t i vùng promoter gen p16INK4v i b nhung th vú.
M t cách t ng quát, tính toán đ u tiên v i hai phơn nhómμ nhóm m u b nh (ung th ) vƠ nhóm m u lƠnh (v i ung th nh ng m c b nh khác v vú).
Nhóm m u b nh lƠ sinh thi t mô đ c thu nh n t b nh vi n H Y D c Tp. HCM. M t s ch tiêu đánh giá tính ch t c a b nh (ung th vú) d a trên đ c đi m b nh h c bao g mμ giai đo n b nh (t giai đo n I đ n giai đo n IV).
Nhóm m u lƠnh (v i ung th ) nh ng m c các b nh lỦ khác v vú (kèm theo ch đ nh ph u thu t l y sinh thi t mô vú c a các bác s .
K t qu th ng kê cho th y tính ch t methyl hóa t i các v trí CpG vùng promoter gen p16INK4đ c kh o sát trong nghiên c u nƠy lƠ m t đ c tr ng c a b nh ung th vú, (đ c trình bƠy B ng 3.14, B ng ph l c 1).
B ng 3.14. M i t ng quan gi a t l methyl hóa t i vùng promoter gen p16INK4v i ung th vú
Lo i m u p16
INK4 Giá tr p*
Không methyl Methyl T ng M u lƠnh 2 (66,67%) 1 (33,33%) 3 (30%) M u ung th
vú 3 (42,86%) 4 (57,14%) 7 (70%)
4 (40,0%) 6 (60%) 10 (100%) p = 0,6726 p* > 0,05, Th ng kê b ng ph n m m Medcal(B , 2014)
Phơn tích chi ti t h n đ i v i các ch tiêu c n lơm sƠng (tu i) vƠ lơm sƠng (các đ c đi m mô b nh) nh m xác đ nh m i t ng quan gi a tính ch t methyl hóa v i ung th vú, ti n hƠnh ghi nh n các k t qu sau (B ng 3.14, B ng ph l c 2).
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B ng 3.15. M i t ng quan gi a t l methyl hóa t i vùng promoter gen p16INK4v i các y u t lơm sƠng trên b nh nhơn ung th vú
Nhóm tu i
M u b nh
Methyl p16INK4 Không methyl p16INK4 N1 (<40) 3 (50,0%) 1 (25,0%) N2 (40 - 50) 2 (33,3%) 1 (25,0%) N3 (>50) 1 (16,7%) 2 (50,0%) Giá tr p* 0,5241 Giai đo n b nh I 2 (50%) 0 (0%) II 2 (50%) 1 (33,3%) III 0 (0%) 1 (33,3%) IV 0 (0%) 1 (33,3%) Giá tr p* 0,2330 p* > 0,05, Th ng kê b ng ph n m m Medcal(B , 2014)
Ghi chúμ m u mô vú c a các b nh nhơn tu i nh h n 40, t 40 - 50 vƠ cao h n tu i 50 l n l t lƠ N1, N2, N3. M u mô vú trong giai đo n I, II, III, IV.
i v i y u t ắnhóm tu i” c a các b nh nhơn đ c nghiên c uμ Nhóm b nh nhơn N1 (có đ tu i < 40) chi m t l ph n tr m cao nh t trong các nhóm tu i kho ng 50,0% , đi u nƠy ch ng t nguy c ung th vú tr c giai đo n ti n mƣn kinh. Phơn tích th ng kê, cho th y y u t nhóm tu i vƠ m c đ methyl hóa gen p16INK4 không có s khác bi t có Ủ ngh a khi giá tr p - value b ng 0,5241 cao h n 0,05 (đ c trình bƠy B ng 3.14, B ng ph l c 2).
i v i y u t ắgiai đo n” ung th μ s li u đ c trình bƠi B ng 3.14, B ng ph l c 3, nh n th y trong các giai đo n ung th vú, m c đ methyl hóa trong giai đo n I, II có ph n tr m cao nh t chi m kho ng > 50,0% hay nói cách khác methyl hóa đ c bi u hi n s m trong quá trình sinh u vƠ quá trình b nh hóa c a ung th vú. Tuy nhiên, giá tr p - value đ t 0,2330 cao h n 0,05 nên th ng kê không có Ủ ngh a.
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3.3.5. Kh o sát m c đ liên quan (t su t chênh - Odd ratio - OR vƠ nguy c t ngđ i - relative risk - RR) gi a tính ch t methyl hóa v i ung th
T su t chênh (Odd ratio) vƠ y u t nguy c t ng đ i (ralative Risk) dùng đ đánh giá hay đo l ng m c đ m nh y u c a m i liên quan m c đ methyl hóa v i lo i m u ung th vú (m u lƠnh vƠ m u ung th ).
K t qu th ng kê cho th y, t su t chênh (OR = 2,6667) vƠ y u t nguy c (RR = 2,0000) có giá tr p - value l n l t lƠ 0,4968; 0,5087 v i p > 0,05 không có s khác bi t trong th ng kê. Nguyên nhơn lƠ s m u nghiên c u còn h n h p, n u t ng s l ng m uung th vú có kh n ng th hi n đ c s t ng quan v m c đ methyl hóa v i các lo i m u (m u lƠnh vƠ m u ung th ).
B ng 3.16. M c đ liên quan gi a tính ch t methyl hóa t i vùng promoter gen p16INK4v i ung th vú
Lo i m u p16
INK4 Giá tr p*
Không methyl Methyl T ng
M u lƠnh 2 (66,67%) 1 (33,33%) 3 (30%) M u ung th vú 3 (42,86%) 4 (57,17%) 7 (70%) 4 (40,0%) 6 (60%) 10 (100%) p* = 0,6726 T su t chênh (OR) 2,6667 0,4968 T s nguy c (RR) 2,0000 0,5087 p* > 0,05, Th ng kê b ng ph n m m Medcal (B, 2014)
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4.1. K T LU N
Thu th p thông tin, xác đ nh v trí vƠ mô t c u trúc vùng promoter, các đ o CpG vƠ exon 1 thu c gen p16INK4a.
Th ng kê t n s methyl hóa gen p16INK4 trên các m u ung th vú, ung th c t cung, ung th ph i, ung th đ i tr c trƠng l n l t lƠ 52,5%, 68,28%, 3λ,6λ%, 83,02% trong t ng s 24 công trình nghiên c u đ c công b trên th gi i.
Kh o sát vƠ đánh giá t n s methyl hóa gen p16INK4 trên 10 m u mô vú đ c đúc paraffin Vi t Nam. T n s methyl hóa các t bƠo ung th , m u lƠnh l n l t lƠ 57,14%, 33,33% đ ng th i xác đ nh m i t ng gi a t l methyl hóa t i vùng promoter gen p16INK4v i các y u t lơm sƠng trên b nh nhơn ung th vú trong đ tu i nh h n 40 (50%) hay giai đo n I (50%) vƠ II (50%). T s OR (t su t chênh - Odd ratio - OR) đ t 2,6667 vƠ t s RR (nguy c t ng đ i - relative risk) đ t 2,0000.
4.2. NGH
Kh o sát th c nghi m gen p16INK4 trên nhi u b nh ung th , t ng c ng c m u kh o sát tình tr ng methyl hóa m u ung th Vi t Nam.
Ti p t c ti n hƠnh th c nghi m kh o sát tính ch t methyl hóa k t h p v i các ghi chúv phơn lo i mô h c đ đánh giá kh n ng s d ng tính ch t methyl hóa nƠy nh m t d u ch ng sinh h c (Bio - marker) h u hi u cho b nh ung th vú Vi t Nam.
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