Surfactant protein DNA methylation: A new entrant in the field of lung cancer diagnostics? (Review)

Abstract

Abstract. Lung cancer is a major cause of cancer-related mortality in both men and women. A 5-year survival of lung cancer patients is only 15% with a negative correlation between progressively advanced lung cancer stage and a 5-year survival period. The only chance for cure is surgical resection if done at the early stage of the disease. Therefore, an early diagnosis and a better prediction of prognosis could decrease mortality. An early diagnosis could provide the opportunity for a therapeutic intervention early in the course of the disease. Genetic alterations in the cancer genome include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. Of the various types of genetic alterations (i.e. gene amplifications, allele deletions, point mutations or deletions and methylation) reported in different tumor types, aberrant promoter methylation of genes is recent and is the focus of the present review. Specifically, we will briefly review the role of promoter methylation in various malignancies and then focus on lung cancer diagnosis and promoter gene methylation with emphasis on the methylation status of genes of the innate host defense, namely the surfactant proteins A and D. Lung cancer prevalence and current statusLung cancer is a major cause of cancer-related mortality in both men and women in industrialized countries and causes more deaths than colorectal, breast and prostate cancer combined (1,2). The overall annual incidence and mortality rate of lung cancer has been estimated to be ~104 million new cases per year and 921,000 deaths in the world, with the highest rates currently observed in Europe and North America (3,4). The incidence and mortality rates are higher for men than for women. However, lung cancer mortality has increased markedly among women since 1960, following an increased prevalence of smoking (5). A high degree of correlation between smoking and lung cancer has been observed. Smoking accounts for 80% of the attributed risk among men and for 45% of the cases among women (6).The 5-year survival of lung cancer patients is only 15%, which is much lower than the survival rate of colorectal (41%) and breast (67%) cancers. This is largely due to the fact that three quarters of lung cancer patients are diagnosed when their disease has spread regionally or distantly (7). There are studies on negative correlation between a 5-year survival period and lung cancer stage (as per TNM classification, where T is characteristic of primary tumor, N is regional lymph node involvement and M is metastasis). A 5-year survival period has been reported as high as 60-70% following resection of stage I lung cancer, while a 5-year survival rate of lung cancer as low as 8-13% has been observed if treatment starts at stages III-IV (8). At present, the only chance of cure is surgical resection at the early stage of the disease, with better prognosis for small tumors compared to larger ones. Thus, an ea...