CYP1A1 genetic polymorphisms, tobacco smoking and lung cancer risk in a French Caucasian population

Our plain-English summary of CYP1A1 genetic polymorphisms, tobacco smoking and lung cancer risk in a French Caucasian population, by C. Bouchardy, H. Wikman, S. Benhamou, et al (Biomarkers, 1997).

The study

• Authors: C. Bouchardy, H. Wikman, S. Benhamou, A. Hirvonen, P. Dayer, K. Husgafvel-Pursiainen
• Journal: Biomarkers
• Published: 1997;2(2):131-4
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The CYP1A1 gene encoding for an enzyme involved in the metabolic activation of important tobacco carcinogens could be implicated in smoking-induced lung cancer. Given the strong association between tobacco smoking and lung cancer, the effect of tobacco smoke exposure has to be taken into account when studying the potential association between lung cancer and CYP1A1 genotypes. The effect of two CYP1A1 genetic polymorphisms (Mspl and IIe-Val) on lung cancer risk were evaluated using peripheral blood DNA from 150 lung cancer patients and 171 controls. The Mspl sitepresent allele was found among 19.3% of both cases and controls and the variant allele Val among 6.7% of cases and 8.8% of controls. Lung cancer risks associated with the Mspl site-present allele (OR= 0.9; 95%Cl: 0.5-1.8) or with the Val allele (OR= 0.8; 95%Cl: 0.3-1.9) were not increased after adjustment for tobacco and asbestos exposures. These results persisted when analyses were stratified on smoking status, daily consumption of tobacco or duration of smoking. Similar findings were obtained when squamous cell or small cell carcinomas were studied separately. This study thus suggests a minor role for the known CYP1A1 gene polymorphisms in predisposition to lung cancer among Caucasian populations.

In plain English

This case-control study, run in 10 French hospitals (nine in Paris) from 1988 to 1992, tested whether two inherited variants of the CYP1A1 gene were linked to lung cancer. The gene makes an enzyme that activates some tobacco carcinogens. The study compared 150 Caucasian patients with squamous cell or small cell lung cancer with 171 Caucasian hospital patients without cancer. All were regular smokers, and most were men. Risks were adjusted for smoking, age, sex, and occupational asbestos and arsenic exposure. About 19% of cases and 7% of controls reported occupational asbestos exposure. Neither variant was linked to a significantly increased risk. The odds ratio was 0.9 (95% confidence interval 0.5 to 1.8) for the MspI variant and 0.8 (0.3 to 1.9) for the Val variant. Results were similar for each cancer type and across smoking levels, including the lightest smokers. The authors concluded that these variants are not important population risk factors for lung cancer in Europeans. They could not estimate risk for people carrying two copies of a variant, because only three were found.

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: Hospital-based case-control study (genetic analysis of blood DNA within a larger case-control study)
• Who was studied: 150 Caucasian patients with histologically confirmed squamous cell (98) or small cell (52) primary lung cancer, and 171 Caucasian hospital patients without previous or current cancer, recruited in 10 hospitals (nine in Paris), France, 1988 to 1992. All were regular smokers. 93% of cases and 95% of controls were male.
• Exposure: Two CYP1A1 gene variants (MspI site-present allele m2 and the Ile-Val variant allele Val) in relation to tobacco smoking. Occupational asbestos and arsenic exposure were recorded by questionnaire and used only as adjustment factors. No fiber type was specified.
• Main results:
  • The MspI variant allele m2 was present in 19.3% of cases and 19.3% of controls. The Val allele was present in 6.7% of cases and 8.8% of controls.
  • There was no significantly increased risk for all lung cancers combined. The odds ratio was 0.9 (95% CI 0.5 to 1.8) for carriers of m2 and 0.8 (95% CI 0.3 to 1.9) for carriers of Val, adjusted for tobacco and asbestos exposures among other factors.
  • Among the lightest smokers (15 g of tobacco per day or less), the odds ratio was 0.6 (95% CI 0.1 to 2.1) for m2 carriers and 0.9 (95% CI 0.2 to 4.6) for Val carriers.
  • The lack of association persisted when results were split by smoking status, daily consumption or duration of smoking. No significant interaction between genotype and smoking variables was observed.
  • About 19% of cases and 7% of controls reported a history of occupational asbestos exposure (p less than 0.001).
  • Only three subjects carried two copies of a variant (homozygous), all of them lung cancer patients.
• The authors' conclusion: The authors concluded that their data support previous findings that these CYP1A1 variants are not important population risk factors for lung cancer in Europeans. They also suggested a minor role for these variants in predisposition to lung cancer among Caucasians.
• Limitations the authors state:
  • The analysis of interaction between genotype and smoking was probably hampered by small numbers.
  • Risk for people with two copies of a variant could not be estimated. Combining one-copy and two-copy carriers may have diluted any association.
  • The authors could not tell whether the lack of association reflects the rarity of these genotypes in Europeans or a true lack of effect.
  • Because only regular smokers were recruited, tobacco exposure varied very little between cases and controls.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Asbestos Exposure, Squamous Cell, Carcinoma.

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