Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans

Abstract

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.

Mutation analysis of the Epac--Rap1 signaling pathway in cold thyroid follicular adenomas

“…There is, indeed, increasing evidence showing that polymorphisms in specific genes can be associated with diseases, e.g. lung cancer (25) or cardiovascular disease (26). Thus, we investigated 20 healthy control patients for the presence (and incidence) of the Gly-to-Ser mutation.…”

Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans

“…Individual case control studies, as well as pooled and meta analyses have confirmed this hypothesis to some extent, so that for example the deletion of GSTM1 variant was found to be associated with various cancer types, both alone and in combination with other genetic polymorphisms. [7][8][9][10] Careful analysis of the literature reveals a much more murky picture for the GSTT1 gene than for GSTM1. Although one group reported GSTT1 to be a risk factor for lung cancer, 11 the majority of studies have found no association between GSTT1 deletion and cancer as shown by a meta and pooled analysis, 12 and in general there are more negative findings for this variant than for the GSTM1 deletion.…”

Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: A case‐control study in Chinese population

“…Although many studies have shown that GSTM1 null genotype and variant CYP1A1 alleles are associated with an increased risk of lung squamous cell carcinoma (SCC) independent of the ethnic background, the results regarding lung AC risk are still contradictory. [3][4][5][6][7][8][9][10][11] A number of studies have also investigated the association of the genetic polymorphism of CYP2E1 with lung cancer, but the effects remain unclear. 6,[12][13][14][15][16][17][18][19][20][21][22] In the Chinese population, lung cancer is the leading cause of cancer deaths, and while SCC is still the predominant histological type, the rate for lung AC is increasing and AC is already the most common histological type in females.…”