Genetic polymorphisms in the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and prostate cancer susceptibility: A case‐control study in a Han nationality population in Southern China

Abstract

Aim : To investigate the association among the polymorphisms of the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and the risk of prostate cancer (PCa) in a Han nationality population in Southern China. Methods : A case-control study including 225 PCa patients and 250 age-matched controls was conducted. The six polymorphic sites of the CYP 1A1 and CYP2E1 genes were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR technique using genomic DNA isolated from peripheral blood lymphocytes. Results : We found that the CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR, 2.26; 95% CI, 1.09-4.68). In contrast, the CYP2E1 C1/C2 (OR, 0.67; 95% CI, 0.46-0.99) or C2/C2 genotype (OR, 0.31; 95% CI, 0.10-1.00) significantly decreased the risk. Furthermore, the individuals carrying the CYP1A1 Val allele and the CYP2E1 C1/C1 genotype showed the highest risk (OR, 2.50; 95% CI, 1.45-4.29). Though there was no significant difference with smoking history ( P = 0.237) or drinking habit ( P = 0.499) between cases and controls, a deep smoking habit (OR, 2.02; 95% CI, 1.28-3.17) and heavy smoking history (OR, 1.61; 95% CI, 1.04-2.50) significantly increased the susceptibility of PCa after stratification by smoking method and accumulative smoking amount. Moreover, both the CYP1A1 Val allele (OR, 2.82; 95% CI, 1.49-5.35) and CYP2E1 C1/C1 genotype (OR, 2.57; 95% CI, 1.31-5.02) had obvious interaction with heavy smoking history that significantly raised the risk. We also discovered a significant interaction between the CYP2E1 C1/C1 genotype and drinking (OR, 1.85; 95% CI, 1.04-3.28). Conclusions : Individuals carrying the CYP1A1 Val allele or the CYP2E1 C1/C1 genotype with a smoking or drinking habit were at increased risk of PCa, which also showed a positive correlation with exposure dose of tobacco.

Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine

“…Future investigations should validate this result and clarify the underlying mechanisms. A lot of researches are interested in CYP1A1 rs1048943 A[G, and this SNP has been reported to be associated with the risk of lung cancer (Chen et al 2011), breast cancer (Sergentanis and Economopoulos 2010), non-Hodgkin lymphoma (Kim et al 2009), esophageal cancer (Zhuo et al 2009), chronic myeloid leukemia (Taspinar et al 2008), colorectal cancer (Kiss et al 2007), gallbladder cancer (Tsuchiya et al 2007), prostate cancer (Yang et al 2006;Murata et al 2001), and epithelial ovarian cancer (Aktas et al 2002).…”

Smoking and aggressive prostate cancer: a review of the epidemiologic evidence

“…From recent evidence provided by genetic association studies [44][45][46][47][48][49][50], it is likely that the effect of smoking on prostate cancer risk is modified by genetic polymorphisms in the xenobiotic metabolism pathway. Although the sample sizes of these studies were limited, the results for the glutathione S-transferase mu (GSTM1) polymorphism and smoking were fairly consistent: smokers with a GSTM1 null phenotype appear to have elevated risk for prostate cancer.…”

Cigarette smoking during pregnancy: Chromosome translocations and phenotypic susceptibility in mothers and newborns

“…Rare genetic variants with high penetrance contribute to approximately 5% of all cancers, whereas the remaining cases are largely attributed to gene-gene and gene-environment interactions. Genetic polymorphisms that increase the risk for cancer among smokers have been identified [33-36]. Inherent genetic susceptibility to the effects of genotoxic exposures can be assessed by evaluating the sensitivity of peripheral blood lymphocytes to bleomycin in vitro [37-39].…”