Genetic polymorphisms of cytochrome P4501A1 and oesophageal squamous-cell carcinoma in Taiwan

Abstract

Several in vitro studies have demonstrated that genetic polymorphisms result in functionally significant changes in cytochrome p4501A1 (either CYP1A1 MspI or exon 7) but the few epidemiologic studies of these polymorphisms in oesophageal squamous-cell carcinoma have been inconclusive. These inconclusive results motivated us to further examine the relationship between CYP1A1 MspI and exon 7 polymorphisms and risk of oesophageal cancer. In total, 146 cases of oesophageal squamous-cell-carcinoma and 324 control cases (a total of 470 cases) were genotyped from records at three Taiwan hospitals. No significant association was noted for the CYP1A1 MspI polymorphism variable between carcinoma and control cases. In contrast, the frequency of Ile/Ile, Ile/Val, and Val/Val in exon 7 was 68 (46.6%), 62 (42.5%), and 16 (11.0%) in carcinoma cases and 179 (55.3%), 127 (39.2%), and 18 (5.6%) in control cases, respectively. After factoring out other potential contributing factors, patients with Val/Val showed a 2.48 (95% CT=1.15 -5.34) greater risk of developing oesophageal cancer than those with Ile/Ile. A slightly (albeit not significantly) greater risk was identified in subjects with Ile/Val (OR=1.34; 95% CI=0.86 -2.07). These findings suggest that an exon 7 polymorphism, not a MspI polymorphism, in CYP1A1 may be pivotal in the development of oesophageal cancer.

CYP1A1 Genetic Polymorphisms and Risk for Esophageal Cancer: a Case-control Study in Central China

“…But associations were null after adjusting for age, gender, smoking, drinking and family history of cancer. This result is consistent with the study of Wu et al (2002). Guo et al (2005) found that individuals with the MspI T/C or C/C genotype had a higher risk of developing esophageal cancer than those with the T/T genotype (OR:1.93,95%CI:1.01-3.84).…”

Cytochrome P450 in Cancer Susceptibility and Treatment

“…Conflicting results have been published regarding the association of CYP1A1 polymorphisms with risk of esophageal cancer in Asians and Caucasians [85][86][87][88][89][90]. In one study, CYP1A1 MspI T/C polymorphism was not associated with esophageal cancer [91].…”

Smoking and susceptibility to thyroid cancer: an inverse association with CYP1A1 allelic variants

“…Two genetic polymorphisms of the CYP1A1 gene have been reported to be associated with differences in the activity of the AHH enzyme activity -an isoleucine to valine substitution in exon 7 (m2 polymorphism) and a thymine/cytosine point mutation in the MspI restriction site (m1 polymorphism; Autrup 2000). Cytochrome P4501A1 (CYP1A1) m1 and m2 gene variants have been shown to be in close linkage disequilibrium and to be associated with a more inducible form of CYP1A1 (Wu et al 2002). The ensuing higher levels of the corresponding enzymes would result in an increased capacity to activate polycyclic aromatic hydrocarbons, producing highly reactive electrophilic intermediates that might damage DNA (Kawajiri et al 1990).…”