Abstract
The polymorphic gene NAT2 is a major determinant of N-acetyltransferase activity and, thus, may be responsible for differences in one’s ability to bioactivate heterocyclic amines, a class of procarcinogens in cooked meat. An unusually marked geographic variation in enzyme activity has been described for NAT2. The present study re-examines the international direct correlation reported for meat intake and colorectal cancer (CRC) incidence, and evaluates the potential modifying effects of NAT2 phenotype and other lifestyle factors on this correlation. Country-specific CRC incidence data, per capita consumption data for meat and other dietary factors, prevalence of the rapid/intermediate NAT2 phenotype, and prevalence of smoking for 27 countries were used. Multiple linear regression models were fit and partial correlation coefficients (PCCs) were computed for men and women separately. Inclusion of the rapid/intermediate NAT2 phenotype with meat consumption improved the fit of the regression model for CRC incidence in both sexes (males—R 2 = 0.78, compared to 0.70 for meat alone; p for difference in model fit—0.009; females—R 2 = 0.76 compared to 0.69 for meat alone; p = 0.02). Vegetable consumption (inversely and in both sexes) and fish consumption (directly and in men only) were also weakly correlated with CRC, whereas smoking prevalence and alcohol consumption had no effects on the models. The PCC between NAT2 and CRC incidence was 0.46 in males and 0.48 in females when meat consumption was included in the model, compared to 0.14 and 0.15, respectively, when it was not. These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype.
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Abbreviations
- NAT2:
-
N-acetyltransferase-2
- CRC:
-
Colorectal cancer
- FAO:
-
Food and Agriculture Organization of the United Nations
References
Parkin DM, Pisani P, Ferlay J (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54:594–606
Hill MJ (1999) Meat and colorectal cancer. Proc Nutr Soc 58:261–264
Sandhu MS, White IR, McPherson K (2001) Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach. Cancer Epidemiol Biomarkers Prev 10:439–446
Norat T, Lukanova A, Ferrari P, Riboli E (2002) Meat consumption and colorectal cancer risk: dose–response meta-analysis of epidemiological studies. Int J Cancer 98:241–256
Kampman E, Slattery ML, Bigler J, et al (1999) Meat consumption, genetic susceptibility, and colorectal cancer risk: a United States multicenter case–control study. Cancer Epidemiol Biomarkers Prev 8:15–24
Hein DW (2002) Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutat Res 506–507:65–77
Sinha R, Rothman N, Brown ED, et al (1994) Pan-fried meat containing high levels of heterocyclic aromatic amines, but low levels of polycyclic aromatic hydrocarbons induces cytochrome P450 1 A2 activity in humans. Cancer Res 54:6154–6159
Le Marchand L, Sivaraman L, Frankie AA, et al (1996) Predictors of N-acetyltransferase activity: should caffeine phenotyping and NAT2 genotyping be used interchangeably in epidemiological studies? Cancer Epidemiol Biomarkers Prev 5:449–455
Deitz AC, Rothman N, Rebbeck TR, et al (2004) Impact of misclassification in genotype-exposure interaction studies: example of N-acetyltransferase 2(NAT2), smoking and bladder cancer. Cancer Epidemiol Biomarkers Prev 13:1543–1546
Brockton N, Little J, Sharp L, Cotton SC (2000) N-acetyltransferase polymorphisms and colorectal cancer: a HuGe review. Am J Epidemiol 151:846–861
Gil JP, Lechner MC (1998) Increased frequency of wildtype arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer. Carcinogenesis 19:37–41
Welfare MR, Cooper J, Bassendine MF, Daly AK (1997) Relationship between acetylator status, smoking, diet and colorectal cancer risk in north-east England. Carcinogenesis 18:1351–1354
Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN (1996) Diet, acetylator phenotype and risk of colorectal neoplasia. Lancet 347:1372–1374
Chen J, Stampfer MJ, Hough HL, et al (1998) A Prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer. Cancer Res 58:3307–3311
Prentice RL (1996) Measurement error and results from analytical epidemiology: dietary fat and breast cancer. J Natl Cancer Inst 88:1738–1747
Armstrong B, Doll R (1975) Environmental factors and cancer incidence and mortality in different countries with special reference to dietary practices. Int J Cancer 15:617–631
Stoneham M, Goldacre M, Seagroatt V, Gill L (2000) Olive oil, diet and colorectal cancer: an ecological study and a hypothesis. J Epidemiol Community Health 54:756–760
Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156
Food Balance Sheets, FAOSTAT (2004) Software. http://faostat.fao.org
Shafey O, Dolwick S, Guindon GE (2003) Tobacco control country profiles. American Cancer Society, Atlanta
Le Marchand L (2005) The predominance of the environment over genes in cancer causation: implications for genetic epidemiology. Cancer Epidemiol Biomarkers Prev 14:1037–1039
Campos FG, Logullo Waitzberg AG, Kiss DR, Waizberg DL, Habr-Gama A, Gama-Rodrigues J (2005) Diet and colorectal cancer: current evidence for etiology and prevention. Nutr Hosp 20:18–25
Ellard GA (1976) Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin Pharmacol Ther 19:610–625
Miller BA, Kolonel LN, Bernstein L, et al (1996) Racial/ethnic patterns of cancer in the United States 1988–1992. National Cancer Institute, NIH Pub. No. 96–4104, Bethesda
Ilett KF, David MD, Detchon P, et al (1987) Acetylation phenotype in colrectal carcinoma. Cancer Res 47:1466–1469
Ladero JM, Gonzalez JF, Benitez J, et al (1991) Acetylator polymorphism in human colorectal carcinoma. Cancer Res 51:2098–2100
Lang NP, Butler MA, Massengill J, et al (1994) Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk of colorectal cancer or polyps. Cancer Epidemiol Biomarkers Prev 3:675–682
Le Marchand L, Hankin JH, Wilkens LR, et al (2001) Combined effects of well-done red meat, smoking, rapid N-acetyltransferase 2 and CYP1A2 phenotypes in increasing colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 10:1259–1266
Glade MJ (1997) Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, AICR
Block G, Patterson B, Subar A (1992) Fruit, vegetables and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18:1–29
Acknowledgments
This work was initiated during a sabbatical by Dr Le Marchand at the International Agency for Research on Cancer, Lyon, France. The contributions of Drs A. Lukanova, M. Parkin and T. Norat to this work are gratefully acknowledged. Grant support: National Cancer Institute grants R25-CA90956 and R01-CA72520.
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Ognjanovic, S., Yamamoto, J., Maskarinec, G. et al. NAT2, meat consumption and colorectal cancer incidence: an ecological study among 27 countries. Cancer Causes Control 17, 1175–1182 (2006). https://doi.org/10.1007/s10552-006-0061-3
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DOI: https://doi.org/10.1007/s10552-006-0061-3