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November 13, 1996, Vol 276, No. 18 >
ARTICLE | November 13, 1996

Smokers and Breast Cancer: Title and subTitle Break'Chemical Individuality' and Cancer Predisposition FREE

Henry J. Lin, MD
[+] Author Affiliations

Corresponding author: Henry J. Lin, MD, Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center, Bldg E4, 1124 W Carson St, Torrance, CA 90502.


JAMA. 1996;276(18):1511-1512. doi:10.1001/jama.1996.03540180067035
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References

What struck Archibald Garrod as black urine on a baby's diaper led to his book on inborn errors of metabolism (1909), viewed then as a small work on "obscure metabolic abnormalities."1,2 More ignored, however, was his idea on disease predisposition and person-to-person variation in biochemical traits, or "chemical individuality" (1931): "[I]n every case of every malady there are two sets of factors at work in the formation of the morbid picture, namely internal or constitutional factors, inherent in the sufferer and usually inherited from his forebears, and external ones which fire the train."3

See also p 1494.

Therefore, Garrod probably would have been pleased to see the article on N-acetyltransferase 2 (NAT2, or acetylator) enzymes, smoking, and breast cancer by Ambrosone et al4 in this week's issue of The Journal, because it follows his way of thinking about disease predisposition. The article suggests that defective acetylator

REFERENCES

1 +
 Inborn Errors of Metabolism  [unsigned book review]. JAMA . 1909;;53:1427.
2 +
Bearn AG. Archibald Garrod and the Individuality of Man . New York, NY: Oxford University Press; 1993;:81.
3 +
Scriver CR, Childs B. Garrod's Inborn Factors in Disease . New York, NY: Oxford University Press; 1989;:170.
4 +
Ambrosone CB, Freudenheim JL, Graham S, et al.  Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk . JAMA . 1996;;276:1494-1501.
5 +
Weber WW. The Acetylator Genes and Drug Response . New York, NY: Oxford University Press; 1987;.
6 +
Hughes HB, Biehl JP, Jones AP, Schmidt LH.  Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis . Am Rev Tuberc . 1954;;70:266-273.
7 +
Devadatta S, Gangadharam PRJ, Andrews RH, et al.  Peripheral neuritis due to isoniazid . Bull World Health Organ . 1960;;23:587-598.
8 +
Evans DAP, Manley KA, McKusick VA.  Genetic control of isoniazid metabolism in man . BMJ . 1960;;2:485-491.
9 +
Jenne JW.  Partial purification and properties of the isoniazid transacetylase in human liver: its relationship to the acetylation of p-aminosalicylic acid . J Clin Invest . 1965;;44:1992-2002.
10 +
Grant DM, Tang BK, Kalow W.  A simple test for acetylator phenotype using caffeine . Br J Clin Pharmacol . 1984;;17:459-464.
11 +
Ohsako S, Deguchi T.  Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver . J Biol Chem . 1990;;265:4630-4634.
12 +
Blum M, Demierre A, Grant DM, Heim M, Meyer UA.  Molecular mechanism of slow acetylation of drugs and carcinogens . Proc Natl Acad Sci USA . 1991;;88:5237-5241.
13 +
Vatsis KP, Martell KJ, Weber WW.  Diverse point mutations in the human gene for polymorphic N-acetyltransferase . Proc Natl Acad Sci USA . 1991;;88:6333-6337.
14 +
Bell DA, Taylor JA, Butler MA, et al.  Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans . Carcinogenesis . 1993;;14:1689-1692.
15 +
Lin HJ, Han C-Y, Lin BK, Hardy S.  Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology . Am J Hum Genet . 1993;;52:827-834.
16 +
Cascorbi I, Drakoulis N, Brockmöller J, Maurer A, Sperling K, Roots I.  Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity . Am J Hum Genet . 1995;;57:581-592.
17 +
Sugimura T.  Multistep carcinogenesis: a 1992 perspective . Science . 1992;;258:603-607.
18 +
International Agency for Research on Cancer, World Health Organization.  Chemistry and analysis of tobacco smoke . In: Tobacco Smoking . Lyon, France: International Agency for Research on Cancer; 1986;:83-126. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol 38.
19 +
Cartwright RA, Glashan RW, Rogers HJ, et al.  Role of N-acetyltransferase phenotypes in bladder carcinogenesis: a pharmacogenetic epidemiological approach to bladder cancer . Lancet . 1982;;2:842-845.
20 +
Hayes RB, Bi W, Rothman N, et al.  N-acetylation phenotype and genotype and risk of bladder cancer in benzidine-exposed workers . Carcinogenesis . 1993;;14:675-678.
21 +
Lang NP, Chu DZJ, Hunter CF, Kendall DC, Flammang TJ, Kadlubar FF.  Role of aromatic amine acetyltransferase in human colorectal cancer . Arch Surg . 1986;;121:1259-1261.
22 +
Ilett KF, David BM, Detchon P, Castleden WM, Kwa R.  Acetylation phenotype in colorectal carcinoma . Cancer Res . 1987;;47:1466-1469.
23 +
Wohlleb JC, Hunter CF, Blass B, Kadlubar FF, Chu DZJ, Lang NP.  Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations . Int J Cancer . 1990;;46;22-30.
24 +
Ladero JM, González JF, Benítez J, et al.  Acetylator polymorphism in human colorectal carcinoma . Cancer Res . 1991;;51:2098-2100.
25 +
Probst-Hensch NM, Haile RW, Ingles SA, et al.  Acetylation polymorphism and prevalence of colorectal adenomas . Cancer Res . 1995;;55:2017-2020.
26 +
Bell DA, Stephens EA, Castranio T, et al.  Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer . Cancer Res . 1995;;55:3537-3542.
27 +
Cascorbi I, Brockmöller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I.  Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer . Cancer Res . 1996;;56:3961-3966.
28 +
Bulovskaya LN, Krupkin RG, Bochina TA, Shipkova AA, Pavlova MV.  Acetylator phenotype in patients with breast cancer . Oncology . 1978;;35:185-188.
29 +
Ladero JM, Fernandez MJ, Palmeiro R, et al.  Hepatic acetylator polymorphism in breast cancer patients . Oncology . 1987;;44:341-344.
30 +
Philip PA, Rogers HJ, Millis RR, Rubens RD, Cartwright RA.  Acetylation status and its relationship to breast cancer and other diseases of the breast . Eur J Cancer Clin Oncol . 1987;;23:1701-1706.
31 +
Webster DJT, Flook D, Jenkins J, Hutchings A, Routledge PA.  Drug acetylation in breast cancer . Br J Cancer . 1989;;60:236-237.
32 +
Ilett KF, Detchon P, Ingram DM, Castleden WM.  Acetylation phenotype is not associated with breast cancer . Cancer Res . 1990;;50:6649-6651.
33 +
Şardaş S, Çok I, Şardaş OS, Ilhan O, Karakaya AE.  Polymorphic N-acetylation capacity in breast cancer patients . Int J Cancer . 1990;;46:1138-1139.
34 +
Agúndez JAG, Ladero JM, Olivera M, Abildúa R, Román JM, Benítez J.  Genetic analysis of the arylamine N-acetyltransferase polymorphism in breast cancer patients . Oncology . 1995;;52:7-11.
35 +
Risch A, Wallace DMA, Bathers S, Sim E.  Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer . Hum Molec Genet . 1995;;4:231-236.
36 +
Doll R.  Nature and nurture: possibilities for cancer control . Carcinogenesis . 1996;;17:177-184.
37 +
Harris H. The Principles of Human Biochemical Genetics . 3rd ed. New York, NY: Elsevier/North-Holland Biomedical Press; 1980;.
38 +
Childs B, Spielman RS.  Harry Harris (1919-94): in memoriam . Am J Hum Genet . 1996;;58:896-898.
39 +
Smith O.  Genetic testing: out of the bottle . Nature Med . 1996;;2:613-614.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
 Inborn Errors of Metabolism  [unsigned book review]. JAMA . 1909;;53:1427.
2 +
Bearn AG. Archibald Garrod and the Individuality of Man . New York, NY: Oxford University Press; 1993;:81.
3 +
Scriver CR, Childs B. Garrod's Inborn Factors in Disease . New York, NY: Oxford University Press; 1989;:170.
4 +
Ambrosone CB, Freudenheim JL, Graham S, et al.  Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk . JAMA . 1996;;276:1494-1501.
5 +
Weber WW. The Acetylator Genes and Drug Response . New York, NY: Oxford University Press; 1987;.
6 +
Hughes HB, Biehl JP, Jones AP, Schmidt LH.  Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis . Am Rev Tuberc . 1954;;70:266-273.
7 +
Devadatta S, Gangadharam PRJ, Andrews RH, et al.  Peripheral neuritis due to isoniazid . Bull World Health Organ . 1960;;23:587-598.
8 +
Evans DAP, Manley KA, McKusick VA.  Genetic control of isoniazid metabolism in man . BMJ . 1960;;2:485-491.
9 +
Jenne JW.  Partial purification and properties of the isoniazid transacetylase in human liver: its relationship to the acetylation of p-aminosalicylic acid . J Clin Invest . 1965;;44:1992-2002.
10 +
Grant DM, Tang BK, Kalow W.  A simple test for acetylator phenotype using caffeine . Br J Clin Pharmacol . 1984;;17:459-464.
11 +
Ohsako S, Deguchi T.  Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver . J Biol Chem . 1990;;265:4630-4634.
12 +
Blum M, Demierre A, Grant DM, Heim M, Meyer UA.  Molecular mechanism of slow acetylation of drugs and carcinogens . Proc Natl Acad Sci USA . 1991;;88:5237-5241.
13 +
Vatsis KP, Martell KJ, Weber WW.  Diverse point mutations in the human gene for polymorphic N-acetyltransferase . Proc Natl Acad Sci USA . 1991;;88:6333-6337.
14 +
Bell DA, Taylor JA, Butler MA, et al.  Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans . Carcinogenesis . 1993;;14:1689-1692.
15 +
Lin HJ, Han C-Y, Lin BK, Hardy S.  Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology . Am J Hum Genet . 1993;;52:827-834.
16 +
Cascorbi I, Drakoulis N, Brockmöller J, Maurer A, Sperling K, Roots I.  Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity . Am J Hum Genet . 1995;;57:581-592.
17 +
Sugimura T.  Multistep carcinogenesis: a 1992 perspective . Science . 1992;;258:603-607.
18 +
International Agency for Research on Cancer, World Health Organization.  Chemistry and analysis of tobacco smoke . In: Tobacco Smoking . Lyon, France: International Agency for Research on Cancer; 1986;:83-126. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol 38.
19 +
Cartwright RA, Glashan RW, Rogers HJ, et al.  Role of N-acetyltransferase phenotypes in bladder carcinogenesis: a pharmacogenetic epidemiological approach to bladder cancer . Lancet . 1982;;2:842-845.
20 +
Hayes RB, Bi W, Rothman N, et al.  N-acetylation phenotype and genotype and risk of bladder cancer in benzidine-exposed workers . Carcinogenesis . 1993;;14:675-678.
21 +
Lang NP, Chu DZJ, Hunter CF, Kendall DC, Flammang TJ, Kadlubar FF.  Role of aromatic amine acetyltransferase in human colorectal cancer . Arch Surg . 1986;;121:1259-1261.
22 +
Ilett KF, David BM, Detchon P, Castleden WM, Kwa R.  Acetylation phenotype in colorectal carcinoma . Cancer Res . 1987;;47:1466-1469.
23 +
Wohlleb JC, Hunter CF, Blass B, Kadlubar FF, Chu DZJ, Lang NP.  Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations . Int J Cancer . 1990;;46;22-30.
24 +
Ladero JM, González JF, Benítez J, et al.  Acetylator polymorphism in human colorectal carcinoma . Cancer Res . 1991;;51:2098-2100.
25 +
Probst-Hensch NM, Haile RW, Ingles SA, et al.  Acetylation polymorphism and prevalence of colorectal adenomas . Cancer Res . 1995;;55:2017-2020.
26 +
Bell DA, Stephens EA, Castranio T, et al.  Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer . Cancer Res . 1995;;55:3537-3542.
27 +
Cascorbi I, Brockmöller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I.  Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer . Cancer Res . 1996;;56:3961-3966.
28 +
Bulovskaya LN, Krupkin RG, Bochina TA, Shipkova AA, Pavlova MV.  Acetylator phenotype in patients with breast cancer . Oncology . 1978;;35:185-188.
29 +
Ladero JM, Fernandez MJ, Palmeiro R, et al.  Hepatic acetylator polymorphism in breast cancer patients . Oncology . 1987;;44:341-344.
30 +
Philip PA, Rogers HJ, Millis RR, Rubens RD, Cartwright RA.  Acetylation status and its relationship to breast cancer and other diseases of the breast . Eur J Cancer Clin Oncol . 1987;;23:1701-1706.
31 +
Webster DJT, Flook D, Jenkins J, Hutchings A, Routledge PA.  Drug acetylation in breast cancer . Br J Cancer . 1989;;60:236-237.
32 +
Ilett KF, Detchon P, Ingram DM, Castleden WM.  Acetylation phenotype is not associated with breast cancer . Cancer Res . 1990;;50:6649-6651.
33 +
Şardaş S, Çok I, Şardaş OS, Ilhan O, Karakaya AE.  Polymorphic N-acetylation capacity in breast cancer patients . Int J Cancer . 1990;;46:1138-1139.
34 +
Agúndez JAG, Ladero JM, Olivera M, Abildúa R, Román JM, Benítez J.  Genetic analysis of the arylamine N-acetyltransferase polymorphism in breast cancer patients . Oncology . 1995;;52:7-11.
35 +
Risch A, Wallace DMA, Bathers S, Sim E.  Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer . Hum Molec Genet . 1995;;4:231-236.
36 +
Doll R.  Nature and nurture: possibilities for cancer control . Carcinogenesis . 1996;;17:177-184.
37 +
Harris H. The Principles of Human Biochemical Genetics . 3rd ed. New York, NY: Elsevier/North-Holland Biomedical Press; 1980;.
38 +
Childs B, Spielman RS.  Harry Harris (1919-94): in memoriam . Am J Hum Genet . 1996;;58:896-898.
39 +
Smith O.  Genetic testing: out of the bottle . Nature Med . 1996;;2:613-614.

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