Skip to main content
Log in

Associations between family history of cancer and genes coding for metabolizing enzymes (United States)

  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objective:Family history of cancer has been a useful tool to identify highly penetrant genes. However, the association between family history and low-penetrance genes that are prevalent in the population is less well understood. While epidemiologists have studied low-penetrance genes in association studies at the population level, geneticists have often favored family studies to identify low-penetrance genes in the same manner that these families have been used to identify high-penetrance genes. In this study, we evaluated the association between family history of cancer and molecular variants of three genes: N-acetyltransferases (NAT2), glutathione-S-transferases (GSTM-1), and methylenetetrahydrofolate reductase (MTHFR). These genes were examined because of their plausible functional significance and their association with cancer risk in some studies.

Methods:In a large multi-centered study of colon cancer, reported family history of cancer in first-degree relatives was used to classify cases and controls separately as having a family history of colorectal cancer, hormone-related cancers, smoking-related cancers, prostate cancer, and any cancer.

Results:With three weak exceptions, we did not observe significant associations between any of these genes and family history of cancer. The ability of family history to positively predict the presence of variants of low-penetrance genes that may carry an elevated risk ranged from 41% to 60%; low-penetrance variants accurately predicted a family history of cancer 9 to 17% of the time. Assessment of the likelihood of having a family history of cancer given the combination of genetic and environmental factors, showed that those who smoked 20 or more cigarettes per day were more likely to have a family history of a smoking-related cancer irrespective of genotype.

Conclusions:People with a family history of cancer are not more likely to have a variant of low-penetrance genes than those without a family history of cancer. Family studies may not be efficient methods to study low-penetrance genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Whittemore AS, Wu AH, Kolonel LN, et al. (1995) Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 141: 732–740.

    Google Scholar 

  2. Nelson CL, Sellers TA, Rich SS, et al. (1993) Familial clustering of colon, breast, uterine, and ovarian cancers as assessed by family history. Genet Epidemiol 10: 235–244.

    Google Scholar 

  3. Slattery ML, Kerber RA (1994) Family history of cancer and colon cancer risk: the Utah Population Database. J Natl Cancer Inst 86: 1618–1626.

    Google Scholar 

  4. Groden J, Thliveris A, Samowitz W, et al. (1991) Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66: 589–600.

    Google Scholar 

  5. Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium (1993) Genetic linkage analysis in familial breast and ovarian cancer. Results from 214 families. Am J Hum Genet 52: 678–701.

    Google Scholar 

  6. Lang NP, Chu DZJ, Hunter CF, Kendall DC, Flammang TJ, Kadlubar FF (1986) Role of aromatic amine acetyltransferase in human colorectal cancer. Arch Surg 121: 1259–1261.

    Google Scholar 

  7. Rebbeck TR (1997) Molecular epidemiology of the human gluta-thione S-transferase genotypes GSTM-1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6: 733–743.

    Google Scholar 

  8. Chen J, Stampfer MJ, Houg HL, et al. (1998) A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer. Cancer Res 58: 3307–3311.

    Google Scholar 

  9. Chen J, Giovannucci E, Kelsey K, et al. (1996) A methylenetet-rahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56: 4862–4864.

    Google Scholar 

  10. Slattery ML, Potter JD, Caan BJ, et al. (1997) Energy balance and colon cancer: beyond physical activity. Cancer Res 57: 75–80.

    Google Scholar 

  11. Edwards SL, Slattery ML, Mori B, et al. (1994) Objective system for interviwer performance evaluation for use in epidemiologic studies. Am J Epidemiol 140: 1020–1028.

    Google Scholar 

  12. Slattery ML, Caan BJ, Duncan D, et al. (1994) A computerized diet history questionnaire for epidemiologic studies. J Am Diet Assoc 94: 761–766.

    Google Scholar 

  13. Kerber RA, Slattery 6ML (1997) Comparison of self-reported and database-linked family history of cancer data in a case-control study. Am J Epidemiol 146: 244–248.

    Google Scholar 

  14. Frosst P, Blom HJ, Milos R, et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetet-rahydrofolate reductase. Nature Genet 10: 111–113.

    Google Scholar 

  15. Zhong S, Howie 6AF, Ketter B, et al. (1991) Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis 12: 1533–1537.

    Google Scholar 

  16. Bigler J, Chen C, Potter JD (1997) Determination of human NAT2 acetylator genotype by oligonucleotide ligation assay. Biotech-niques 22: 682–690.

    Google Scholar 

  17. Wolf CR, Smith CAD (1994) Metabolic polymorphisms in carcinogen metabolizing enzymes and cancer susceptibility. Br Med Bull 50: 718–731.

    Google Scholar 

  18. Rothman N, Stewart WF, Schulte PA (1995) Incorporating biomarkers into cancer epidemiology: a matrix of biomarker and study design categories. Cancer Epidemiol Biomarkers Prev 4: 301–311.

    Google Scholar 

  19. Zhao LP, Aragaki C, Hsu L, Quiaoit F (1998) Mapping of complex traits by single-nucleotide polymorphisms. Am J Hum Genet 63: 225–40.

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slattery, M.L., Edwards, S.L., Samowitz, W. et al. Associations between family history of cancer and genes coding for metabolizing enzymes (United States). Cancer Causes Control 11, 799–803 (2000). https://doi.org/10.1023/A:1008912317909

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008912317909

Navigation