Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer

Abstract

<jats:p> 1 Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been associated with a number of apparently unrelated cancers, including lung cancer. Emphysema is a common lung disease often found concomitant with lung cancer. Both emphysema and lung cancer may result from chemical and oxidative damage caused by reactive species present in cigarette smoke or released from neutrophils recruited follow ing cigarette smoke induced injury. GSTM1 may protect against such damage through detoxification of cigarette smoke components. Polymorphism of this gene may thus influence susceptibility not just to lung cancer, but to other forms of lung disease. </jats:p><jats:p> 2 Resection specimens from a group of 168 lung cancer patients were assessed for the presence of macro scopic centriacinar and panacinar emphysema. DNA was extracted from archival material and genotyped for the GSTM1 polymorphism using the polymerase chain reaction. A control group of 384 anonymous blood donations was used to determine the frequency of the GSTM1 gene deletion in a random control population. Reverse transcription on lung tissue was performed to investigate mRNA expression of GSTM1 and GSTM4. </jats:p><jats:p> 3 In 57 lung cancer cases with no emphysema there was no association with homozygous deletion of the GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111 patients with emphysema and lung cancer there was an increase in the frequency of deletion (65%, P=0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases there was evidence of both centriacinar and panacinar emphy sema. The frequency of GSTM1 deletion was 70% (Odds ratio 2.11, 0.97 - 3.25). Both GSTM1 and GSTM4 mRNAs were expressed in lung tissue. </jats:p><jats:p> 4 These findings suggest that GSTM1 has a general but rather small protective effect against toxicological injury in the lung which is not specific to cancer. This is of relevance in considering the health effects of exposure to a wide range of reactive chemicals in the environment. </jats:p>

Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis

“…The genetic factors are supposed to be related to this individual susceptibility. Recently, genetic polymorphism of cytochrome P450 [22], microsomal epoxide hydrolase [23], glutathione S-transferase M1 [24], tumour necrosis factor-a [25], and glutathione S-transferase P1 [26] were suggested to have an association with emphysema or COPD.…”

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk

“…The association between GSTM1 gene and COPD has been reported in the past in several populations, including cohorts of Caucasian patients (34,35). The connection between GSTM1 gene and COPD should be considered on the basis that both lung cancer and COPD have a causative relationship with smoke exposure.…”

A review of selected anti-tumour therapeutic agents and reasons for multidrug resistance occurrence

“…Nevertheless, it is still a matter of discussion whether GSTM1 polymorphism alone could confer an increased risk of lung cancer. Indeed, several recent studies reported significant differences in the polymorphism frequency between lung cancer patients and a control population, while others failed to show any connection (Harrison et al 1997;Sun et al 1997). GSTT1 and GSTP1 are members of the family characterized by a high frequency of polymorphism (Pastore et al 2003;Su et al 2003).…”