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August 7, 1991, Vol 266, No. 5 >
ARTICLE | August 7, 1991

Molecular Epidemiology and the Genetics of Environmental Cancer FREE

Peter G. Shields, MD; Curtis C. Harris, MD
[+] Author Affiliations

Reprint requests to Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bldg 37, Room 2C01, Bethesda, MD 20892 (Dr Harris).


JAMA. 1991;266(5):681-687. doi:10.1001/jama.1991.03470050081027
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References

Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments.

(JAMA. 1991;266:681-687)

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2 +
Shields PG, Harris CC.  Environmental causes of cancer. Med Clin North Am . 1990;;74:263-277.
3 +
Yuspa SH, Poirier MC.  Chemical carcinogenesis: from animal models to molecular models in one decade. Adv Cancer Res . 1988;;50:25-70.
4 +
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5 +
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6 +
Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE.  Increased cell division as a cause of human cancer. Cancer Res . 1990;;50:7415-7421.
7 +
Bouck N.  Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. Cancer Cells . 1990;;2:179-185.
8 +
Liotta LA.  Tumor invasion and metastases— role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res . 1986;;46:1-7.
9 +
Bishop JM.  Molecular themes in oncogenesis. Cell . 1991;;64:235-248.
10 +
Hansen MF, Koufos A, Gallie BL, et al.  Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA . 1985;;82:6216-6220.
11 +
Cavenee WK, Murphree AL, Shull MM, et al.  Prediction of familial predisposition to retinoblastoma. N Engl J Med . 1986;;314:1201-1207.
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Friend SH, Bernards R, Rogelj S, et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature . 1986;;323:643-646.
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Liotta LA, Steeg PS, Stetler-Stevenson WG.  Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell . 1991;;64:327-336.
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Hollstein M, Sidransky D, Vogelstein B, Harris CC.  p53 Mutations in human cancers. Science . 1991;;253:49-53.
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Barbacid M.  ras Genes. Ann Rev Biochem . 1987;;56:779-827.
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Brown K, Buchmann A, Balmain A.  Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. Proc Natl Acad Sci U S A . 1990;;87:538-542.
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Hsu IC, Metcalf RA, Sun T, Welsh J, Wang NJ, Harris CC.  p53 Gene mutational hotspot in human hepatocellular carcinomas from Qidong, China. Nature . 1991;;350:427-428.
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Bressac B, Kew M, Wands J, Ozturk M.  Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature . 1991;;350:429-431.
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Figures

Tables

Interactive Graphics

Video

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 +
Harris CC.  Chemical and physical carcinogenesis: advances and perspectives. Cancer Res . In press.
2 +
Shields PG, Harris CC.  Environmental causes of cancer. Med Clin North Am . 1990;;74:263-277.
3 +
Yuspa SH, Poirier MC.  Chemical carcinogenesis: from animal models to molecular models in one decade. Adv Cancer Res . 1988;;50:25-70.
4 +
Weinstein IB.  Growth factors, oncogenes, and multistage carcinogenesis. J Cell Biochem . 1987;;33:213-224.
5 +
Rowley JD.  Molecular cytogenetics: Rosetta Stone for understanding cancer—twenty-ninth GHA Clowes Memorial Award lecture. Cancer Res . 1990;;50:3816-3825.
6 +
Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE.  Increased cell division as a cause of human cancer. Cancer Res . 1990;;50:7415-7421.
7 +
Bouck N.  Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. Cancer Cells . 1990;;2:179-185.
8 +
Liotta LA.  Tumor invasion and metastases— role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res . 1986;;46:1-7.
9 +
Bishop JM.  Molecular themes in oncogenesis. Cell . 1991;;64:235-248.
10 +
Hansen MF, Koufos A, Gallie BL, et al.  Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA . 1985;;82:6216-6220.
11 +
Cavenee WK, Murphree AL, Shull MM, et al.  Prediction of familial predisposition to retinoblastoma. N Engl J Med . 1986;;314:1201-1207.
12 +
Friend SH, Bernards R, Rogelj S, et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature . 1986;;323:643-646.
13 +
Liotta LA, Steeg PS, Stetler-Stevenson WG.  Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell . 1991;;64:327-336.
14 +
Hollstein M, Sidransky D, Vogelstein B, Harris CC.  p53 Mutations in human cancers. Science . 1991;;253:49-53.
15 +
Malkin D, Li FP, Strong LC, et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science . 1990;;250:1233-1238.
16 +
Halevy O, Michalovitz D, Oren M.  Different tumor-derived p53 mutants exhibit distinct biological activities. Science . 1990;;250:113-116.
17 +
Horsfall MJ, Gordon AJ, Burns PA, Zielenska M, van der Vliet GM, Glickman BW.  Mutational specificity of alkylating agents and the influence of DNA repair. Environ Mol Mutagen . 1990;;15:107-122.
18 +
Barbacid M.  ras Genes. Ann Rev Biochem . 1987;;56:779-827.
19 +
Brown K, Buchmann A, Balmain A.  Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. Proc Natl Acad Sci U S A . 1990;;87:538-542.
20 +
Newcomb EW, Diamond LE, Sloan SR, Corominas M, Guerrerro I, Pellicer A.  Radiation and chemical activation of ras oncogenes in different mouse strains. Environ Health Perspect . 1989;;81:33-37.
21 +
Hsu IC, Metcalf RA, Sun T, Welsh J, Wang NJ, Harris CC.  p53 Gene mutational hotspot in human hepatocellular carcinomas from Qidong, China. Nature . 1991;;350:427-428.
22 +
Bressac B, Kew M, Wands J, Ozturk M.  Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature . 1991;;350:429-431.
23 +
Gonzalez FJ, Crespi CL, Gelboin HV.  DNA-expressed human cytochrome P450s: a new age of molecular toxicology and human risk assessment. Mutat Res . 1991;;247:113-127.
24 +
Loeb LA.  Endogenous carcinogenesis: molecular oncology into the twenty-first century—presidential address. Cancer Res . 1989;;49:5489-5496.
25 +
Floyd RA.  The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis . 1990;;11:1447-1450.
26 +
Ames BN.  Mutagenesis and carcinogenesis: endogenous and exogenous factors. Environ Mol Mutagen . 1989;;14( (suppl 16) ):66-77.
27 +
Gerson SL.  Regeneration of 06-alkylguanineDNA alkyltransferase in human lymphocytes after nitrosourea exposure. Cancer Res . 1988;;48:5368-5373.
28 +
Scudiero DA, Meyer SA, Clatterbuck BE, Mattern MR, Ziolkowski CH, Day RS.  Sensitivity of human cell strains having different abilities to repair 06-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas. Cancer Res . 1984;;44:2467-2474.
29 +
Myrnes B, Giercksky KE, Krokan H.  Interindividual variation in the activity of O6 -methyl guanine-DNA methyltransferase and uracil-DNA glycosylase in human organs. Carcinogenesis . 1983;;4:1565-1568.
30 +
Grafstrom RC, Pegg AE, Trump BF, Harris CC.  O6-alkylguanine-DNA alkyltransferase activity in normal human tissues and cells. Cancer Res . 1984;;44:2855-2857.
31 +
Harris CC.  Interindividual variation among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis . 1989;;10:1563-1566.
32 +
Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR.  Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature . 1984;;312:169-170.
33 +
Caporaso NE, Tucker MA, Hoover R, et al.  Lung cancer and the debrisoquine metabolic phenotype. J Natl Cancer Inst . 1990;;85:1264-1272.
34 +
Petruzzelli S, Camus AM, Carrozzi L, et al.  Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients. Cancer Res . 1988;;48:4695-4700.
35 +
McLemore TL, Adelberg S, Liu MC, et al.  Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke—induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas. J Natl Cancer Inst . 1990;;82:1333-1339.
36 +
Kouri RE, McKinney CE, Slomiany DJ, Snodgrass DR, Wray NP, McLemore TL.  Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res . 1982;;42:5030-5037.
37 +
Bartsch H, Hietanen E, Petruzzelli S, et al.  Possible prognostic value of pulmonary AH-locus-linked enzymes in patients with tobacco-related lung cancer. Int J Cancer . 1990;;46:185-188.
38 +
Fearon ER, Vogelstein B.  A genetic model for colorectal tumorigenesis. Cell . 1990;;61:759-767.
39 +
Shields PG, Weston A, Sugimura H, et al.  Molecular epidemiology: dosimetry, susceptibility and cancer risk.  In: Vanderlaan M, Stanker LH, Watkins BE, Roberts DW, eds. Immunoassays for Trace Chemical Analysis: Monitoring Toxic Chemicals in Humans, Food, and the Environment . Washington, DC: Americal Chemical Society; 1991;:186-206.
40 +
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