Association between ADH2 /ALDH2 genetic polymorphism and habit of alcohol drinking and the susceptibility of rectal cancer

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1 CHIN J CANCER PREV TREA T,October 2007,Vol114 No g 1, 1, 1, Takezaki Toshiro 2, 3, Tajima Kazuo 4, 1,5 1., , , 3., , , 5., Association between ADH2 /ALDH2 genetic polymorphism and habit of alcohol drinking and the susceptibility of rectal cancer J IA N G A i2ren 1, GAO Chang2ming 1, WU J ian2z hong 1, Takez aki Toshi ro 2, CAO J ia 3, Tajima Kaz uo 4, S H EN Hong2bing 1,5 1. Cancer Center of N anjing Medical University, J iangsu Province Institute of Cancer Research, N anjing , P. R. China 2. Kagoshima Universit y Graduate S chool of Medical and Dental S ciences, Kagoshima , J a pan 3. School of Military Prevention Medicine, Thi rd M ilitary Medical Universit y, Chongqing , P. R. China 4. Division of Epi demiology and Prevention, A ichi Cancer Center Research I nstitute, N agoy a , J apan 5. School of Public Health, N anj ing Medical Universit y, N anj ing , P. R. China :2 (AD H2) 2 (ALD H2) : 2,PCR2D H2 PLC AD H2/ ALD H2, : 1), ( OR = 2120, 95 % CI : , P = ) ;2) AD H2 ALD H2 3) AD H2 ALD H2, AD H2 A/ A ALD H2 G/ G, ( OR = 1182, 95 % CI : ) 4), AD H2 A/ A A/ G + G/ G OR 2156 ( 95 % CI : ) (95 % CI : ) ; ALD H2 G/ G OR (95 % CI : ) : ; AD H2 A/ A ALD H2 G/ G ;ALD H2 G/ A + A/ A,2007,14 (19) : [ ABSTRACT] OBJECTIVE : To study the association be2 tween AD H2/ ALD H2 genetic polymorphism and habit of alcohol drinking and the susceptibility of rectal cancer. METHODS : A case control study was conducted with 210 patient s with rectal cancer and 439 population based con2 trols in Jiangsu Province, China. AD H2 and ALD H2 geno2 types were detected by PCR2D HPLC. RESULTS : 1) Alco2 hol drinking was associated with the increased risk of rectal cancer (adjusted OR = 21 20, 95 %CI : ). 2) In2 dividuals with AD H2 A/ A and ALD H2 G/ G genotypes had an elevated risk with rectal cancer ( adjusted OR = 1182, 95 %CI : ). 3) Drinkers with AD H2 A/ A or A/ G + G/ G and those with ALD H2 G/ G were at a signifi2 cantly risk of developing rectal cancer (adjusted ORAD H2 A/ A = 2156, 95 % CI : , ORAD H2 A/ G + G/ G = 2110, 95 % CI : , ORALD H2 = 2163, 95 % CI : ). CONCL USION : Alcohol drinking might be a risk factor of rectal cancer, and the interaction might exist between polymorphisms of AD H2 A/ A and ALD H2 G/ G. ALD H2A allele may be a decreased risk fac2 tor of rectal cancer. Chin J Cancer Prev T reat,2007,14 (19) : ( ) ; ( ) ( ),,,, Tel : E2mail com,,,,,, Tel : E2mail edu. cn

2 1446, 2 2 ;2 ;2 ;; [ KEYWORDS] rectal neoplasms ; alcoholdehy drogenase 2 ; aldehydede hydrogenase2 ; polymorphism ; case2control study R A (2007) ,,,,,, DNA, DNA, DNA 80 %(ADH) ADH, (ALDH),, 2 (ADH2) 2 (ALDH2),, 2 ( PCR2DHPLC), ADH2 ALDH2, , (132 ) (58 ) (20 ) 210 ( ) 5 (,1 ) 3 (, 1 ), ( 2 ), 1 2, 2, 439, 1. 2,,,,, (buffy coat) Q IAamp DNA DNA,DNA PCR PCR : AD H2, 5 2GGGCT T2 TA GACT GAA TAACCT T GG23, 5 2A GGGAA2 A GA GGAAACTCCT GA23 ;ALDH2, 5 2T2 GCTA T GA T GT GT T T GGA GCC23, 5 2GGC T2 CCGA GCCACCA2325 L, 20 p mol,4 dn TP (215 mmol/ L) 215L, MgCl2 (215 mmol/ L ) 210 L, 10 Buffer 215 L, hot Taq ( ) 1 IU :95 7 min, 35 (95 30 s, s, s),72 5 min 94 4 min,011 / s 25, PCR D HPL C ( WAV E23500, Transgenomic, U SA), 011 mol/ L N2 ( TEAA,), 019 ml/ min, applica2 tion type mutation, D HPL C, D H PL C,,, D H PL C ( ),D HPL C (SOP),D HPL C DNA 100 % [ 1 ] AD H2 ALD H2 Logistic (OR) 95 % CI SAS 810 > 1, 20 g , ,, P = ( ), ( ),, P = 01024,, P = 01316, P = (1)

3 CHIN J CANCER PREV TREA T,October 2007,Vol114 No [ n( %) ] 2 P 439 (100. 0) 210 (100. 0) 223 (50. 8) 125 (59. 5) 216 (49. 2) 85 (40. 5) () < (9. 6) 30 (14. 3) (17. 1) 39 (18. 6) (34. 2) 58 (27. 6) (29. 8) 59 (28. 1) > (9. 3) 24 (11. 4) x - s() t ADH2 ALDH2 DHPLC ADH2 ALDH2 DHPLC 1 1 ADH2 ALDH2 DHPLC X : ; Y :260 nm ; :60 ;1 : ( G/ A) ;2 :G/ G A/ A ; A : AD H2 D HPL C ;B : ALD H2 D HPLC 2. 3 ADH2 ALDH2 AD H2 A/ A A/ G G/ G5110 % 4014 %816 %, % %91 1 % ; ALD H2 G/ G G/ A A/ A 6811 % 2910 % 219 %, 6017 % 3410 %513 % Handy2Weinberg, , P > 0105 AD H2 ALD H2, , P > 0105, AD H2 ALD H2, AD H 2A/ A,A/ G OR,, P = ;,ALD H2 G/ G,A/ A OR,, P = 01128, OR 2120 ( 95 % CI : ), 2120 (2) 2. 4 ADH2 ALDH2 AD H2 ALD H2 Logistic 3,AD H2 A/ G + G/ G ALD H2A/ G + A/ A, AD H2 A/ A ALD H2 G/ G,OR 1182 (95 % CI : ) 2. 5 ADH2 ALDH2 ADH2 ALDH2 Logistic 4 ADH2 A/ G + G/ G, ADH2 A/ A, OR 2156 (95 % CI: ) ALDH2 G/ A + A/ A, ALDH2 G/ G, OR 2163 (95 %CI: ),ALDH2A OR 1148, (95 %CI: ) 3 AD H2 ALD H2 AD H2 3 G143A,AD H2 A/ A AD H2 ALD H2 12 G1510A,ALD H2 [2 ]

4 1448, ADH2 ALDH2 [ n( %) ] ORa (95 % CI) 2 P AD H2 A/ A 107 (51. 0) 204 (46. 6) A/ G 85 (40. 4) 194 (44. 3) ( ) G/ G 18 (8. 6) 40 (9. 1) ( ) A/ G + G/ G 103 (49. 0) 234 (53. 4) ( ) A ALD H2 G/ G 143 (68. 1) 266 (60. 7) G/ A 61 (29. 0) 149 (34. 0) ( ) A/ A 6 (2. 9) 23 (5. 3) ( ) G/ A + A/ A 67 (31. 9) 172 (39. 3) ( ) G (57. 1) 327 (74. 5) (42. 9) 112 (25. 5) ( ) ORs a Logistic ; 1, ADH2 ALDH2 AD H2 ALD H2 OR a (95 % CI) A/ G + G/ G G/ A + A/ A A/ A G/ A + A/ A ( ) A/ G + G/ G G/ G ( ) A/ A G/ G ( ) :ORs a Logistic 4 ADH2 ALDH2 OR a (95 %CI) AD H2 A/ G + G/ G A/ A ( ) A/ G + G/ G ( ) A/ A ( ) ALD H2 G/ A + A/ A G/ G ( ) G/ A + A/ A ( ) G/ G ( ) :ORs a Logistic AD H2 ALD H2 [11 ], AD H2 G > 85 %, AD H2 A > 85 % [3 ] Muramat su [4 ],AD H2 A 68 %,, ( = , P = 01000), AD H2 A 7112 %6817 %, ALD H2A 16 %, 27 % ALD H2A [5 ] ALD H2 A,, Logistic 1714 %2212 %, [6 ] Hori [7 ], AD H2 G/ G ; AD H2 G/ G ALD H2 G/ A,OR 1719 ( P = 01000) AD H2 Yokoyama [8 ],ALD H2A Yokoyama [ 9 ] 1 002, ALD H2A OR [10 ], ALD H2 A/ A AD H2 ALD H2 AD H2 ALD H2, AD H2 A/ A ALD H2 G/ G, OR 1182 (95 % CI : ),, AD H2 ALD H2,

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