Correlation of CYP1A1, GSTP1 and GSTM1 gene polymorphisms and lung cancer risk among smokers

Abstract

Abstract. Lung cancer is the leading cause of cancer mortality worldwide and tobacco smoking has been established as its biggest risk factor. Cigarette smoke contains several carcinogens. Most of them need to be activated by phase I enzymes, such as cytochrome P450 (CYP), while phase II enzymes, such as glutathione S-transferases are responsible for the detoxification of activated forms. The present study aimed to determine the role of CYP1A1, GSTP1 and GSTM1 gene polymorphisms in smoking-related lung cancer risk. It also aimed to investigate the association of the above polymorphisms with clinicopathological parameters, as well as their effect on survival. One hundred newly diagnosed lung cancer patients with advanced disease and 125 healthy controls with a smoking history participated in the study. The participants were screened for the presence of the following polymorphisms: MspI (CYP1A1), Ile105Val (GSTP1) and GSTM1 deletion. The above polymorphisms were also examined with regards to gender, age, histological type and survival. GSTP1 Ile/Val and GSTM1-null genotypes were associated with increased lung cancer risk and the presence of the combination of the three non-wild-type genotypes increases susceptibility to lung cancer (OR 3.328, 95% CI=1.681-6.587, p=0.001). In the non-small cell lung cancer group, the GSTP1 homozygous variant was significantly associated with increased lung cancer risk (p=0.008) and shorter survival. The results of this study suggest that the GSTP1 Ile/ Val genotype and GSTM1 deletion contribute to increased lung cancer susceptibility. Moreover, GSTP1 Val/Val genotype is associated with increased lung cancer risk and shorter survival in non-small cell lung cancer patients.

Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

“… 7 Among smokers, previous studies have revealed associations between the genes GSTM1 , GSTT1 , and GSTP1 and higher ORs for lung cancer. 1 , 8 , 9 However, among never smokers a recent investigation found no significant association between single or combined genotypes of GSTM1 , GSTT1 , or GSTP1 and lung cancer risk. 10 Additionally, TP53 mutations have also been highlighted more frequently in lung carcinomas arising in smokers than in never smokers.…”

Frequency of CYP450 enzyme gene polymorphisms in the Greek population: review of the literature, original findings and clinical significance

“…CYP1A1 gene polymorphisms have been studied in association with the occurrence of several cancers in different populations. In the Greek population, CYP1A1 T3801C (*2A allele or MspI) polymorphism was not associated with smoking-related lung cancer risk in a study that included 100 patients with histologically or cytologically documented advanced lung cancer [94] or with the development of cervical intraepithelial neoplasia, in a study in 166 women with history of cervical intraepithelial neoplasia [95]. Similarly, CYP1A1*2A allele was not associated with breast cancer risk in a study in 207 female breast cancer patients [96].…”

Overexpression of MCPH1 inhibits the migration and invasion of lung cancer cells

“…Lung cancer is the leading cause of cancer death worldwide. 1 , 2 There are more than 10 million deaths from lung cancer every year, largely because of the lack of effective early diagnosis and treatment. Despite improvements in the availability and sophistication of lung cancer treatment regimens, such as radiotherapy, chemotherapy, and surgery, the 5-year survival rate remains only 15% and has not increased significantly over the past 20 years.…”