Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County

Our plain-English summary of Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County, by S.J. London, A.K. Daly, J. Cooper, et al (Pharmacogenetics, 1996).

The study

• Authors: S.J. London, A.K. Daly, J. Cooper, C.L. Carpenter, W.C. Navidi, L. Ding, J.R. Idle
• Journal: Pharmacogenetics
• Published: 1996;6(2):151-8
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Genetic polymorphisms in the activation or detoxication of carcinogens, such as those in tobacco smoke, may produce differences in individual susceptibility to lung cancer. The cytochrome P450 CYP2E1 is an enzyme involved in the metabolism of nitrosamines in tobacco smoke. A polymorphism of CYP2E1 detectable by the restriction enzyme Rsa I may be functionally important because it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYP2E1 transcription. It is conceivable that this CYP2E1 Rsa I polymorphism might contribute to differences in susceptibility to lung cancer. We conducted a case-control study of patients with incident lung cancer and population controls in Los Angeles County to examine the association between the CYP2E1 Rsa I polymorphism and lung cancer risk among African-Americans and Caucasians. Samples of white blood cell DNA sufficient for determination of the CYP2E1 Rsa I genotype by a polymerase chain reaction-based assay were obtained from 341 cases and 706 controls with data on lifetime smoking history. No subjects were homozygous for the CYP2E1 Rsa I rare c2 allele. The rare c2 allele was not associated with an increased risk of lung cancer (adjusted odds ratio, OR 0.72; 95% confidence interval, CI = 0.35-1.46). Among the population controls the percentage of subjects carrying the rare c2 allele was lower (p = 0.002) among African-Americans (2%) compared with Caucasians (8%). However, the association between the CYP2E1 Rsa I genotype and lung cancer risk did not differ between ethnic groups. There was no important association between the CYP2E1 Rsa I genotype and lung cancer risk in analyses stratified by cell-type, smoking history, gender, occupational asbestos exposure, and dietary intake of antioxidants vitamin C, vitamin E or beta carotene. Due to the low frequency of the c2 allele in these populations, larger studies would be necessary to rule out a modest association between the CYP2E1 Rsa I polymorphism and lung cancer risk.

In plain English

This Los Angeles County case-control study asked whether a rare form of the CYP2E1 gene, the c2 allele detected with the enzyme Rsa I, was linked to lung cancer among African-Americans and Caucasians. It analyzed 341 people with newly diagnosed lung cancer and 706 population controls who gave blood DNA and were interviewed about smoking and work-related asbestos exposure. A physician graded job titles and tasks as not exposed or possibly exposed to asbestos. No one carried two copies of the c2 allele. Carrying one copy was not associated with an increased lung cancer risk (odds ratio 0.72, 95% confidence interval 0.35–1.46), and the authors wrote that larger studies were needed to rule out a modest association. Among controls, 2% of African-Americans and 8% of Caucasians carried the c2 allele (p = 0.002). The association did not differ appreciably by race, sex, asbestos exposure, or intake of vitamin C, vitamin E or betacarotene, nor significantly by smoking. The authors concluded that their data did not support an important association. Because the allele was rare, they considered CYP2E1's role uncertain.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case-control study of incident lung cancer cases and population controls
• Who was studied: 341 lung cancer cases and 706 population controls in the analysis. Participants were African-American or non-Hispanic Caucasian residents of Los Angeles County aged 40–84, enrolled January 1, 1991 to May 1, 1994. Cases came from 35 hospitals. Controls under 65 were drawn from Department of Motor Vehicles lists and controls 65 and over from Medicare beneficiaries.
• Exposure: The main exposure studied was the CYP2E1 Rsa I genetic polymorphism (rare c2 allele). Occupational asbestos exposure was used only as a factor for subgroup analysis: an occupational medicine physician graded job titles and tasks as not exposed or possibly exposed. No fiber types were specified.
• Main results:
  • No subjects (cases or controls) were homozygous for the c2 allele.
  • Among all subjects, carrying the c2 allele was not associated with an increased lung cancer risk: OR = 0.72 (95% CI 0.35–1.46). Carriers were 13 of 341 cases and 41 of 706 controls.
  • Among controls, the proportion of subjects carrying the c2 allele (heterozygotes, c1c2) was significantly lower in African-Americans (2%) than in Caucasians (8%), p = 0.002.
  • By cell type, an increased risk for carriers was seen only for squamous cell carcinoma, with wide confidence intervals (OR = 1.74, 95% CI 0.69–4.35).
  • The association did not differ appreciably by race, gender, asbestos exposure, or dietary intake of vitamin C, vitamin E or betacarotene.
  • There was no significant difference in the association across smoking strata (never, past, current) or by pack-years.
  • In Table 3, among subjects with no asbestos exposure, the OR for carriers was 1.07 (0.43–2.64).
  • In Table 3, among subjects with some asbestos exposure, the OR for carriers was 0.37 (0.11–1.25).
• The authors' conclusion: The authors concluded that their data do not support an important association between the CYP2E1 Rsa I polymorphism and lung cancer risk among African-Americans or Caucasians. Because the c2 allele is rare in these populations, they considered the role of CYP2E1 in lung cancer susceptibility still uncertain.
• Limitations the authors state:
  • Because the c2 allele is rare in these populations, the study lacked power for a definitive test; larger studies would be needed to rule out a modest association.
  • Response rates were somewhat low. The authors considered bias from this unlikely, since genotype would need to be related to participation.
  • The authors did not identify all persons with newly diagnosed lung cancer in the county and could not enroll all eligible case patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Case-Control Study, Odds Ratio, confidence interval, Asbestos Exposure.

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