Genotypes of GSTM1 and GSTT1: useful determinants for clinical outcome of bladder cancer in Pakistani population

Background: Incidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 [GSTM1] and glutathione S transferase theta 1 [GSTT1] genes are two xenobiotic metabolizing genes in phase II of detoxification process

Aim: The current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population

Method: Bladder cancer cases [236] and control blood samples [270] were screened using phenol chloroform method of DNA extraction followed by multiplex PCR

Results: With respect to age; bladder cancer was more prevalent in age >60 years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated [P < 0.05] with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms [LUTS] and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 [OR 2.24; CI 1.5-3.2; P = 0.0001] and GSTT1 [OR 2.9; CI 1.4-6.1; P = 0.002] gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association [OR 5.3; CI 2.1-13.1; P =0.0001] with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers

Conclusion: This study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population

Red flag symptoms: detailed account of clinicopathological features in young-onset colorectal cancer

BACKGROUND/AIMS: Colorectal cancer has long been considered disease of the West, typically occurring in old age; however, the incidence is rising in Asia. The pattern of disease is quite different in Asia, occurring at a younger age and at an advanced stage. Recognition of disease at an early stage is still a challenge for physicians. Few data are available regarding young-onset colorectal cancer in Pakistan. We conducted this study to fill this gap and provide deeper insight into clinical symptoms and histopathological features of young-onset colorectal cancer. METHODS: We collected data regarding clinical features by directly interviewing patients and obtaining histopathological data from hospital records. Patients aged less than 50 years were included in the study. Statistical analysis was performed using IBM SPSS version 20.0. RESULTS: Results in 105 patients showed mean age at diagnosis was 35.90±9.39, with male predominance; the majority of patients had no family history of colorectal cancer. Most patients had left-sided tumors with advance stage and intermediate grade (grade 2). Mucinous histology was common. Rectal bleeding was the first symptom for left-sided tumors, whereas most of the right-sided lesions presented with sudden obstruction. CONCLUSIONS: Painless rectal bleeding in the early thirties should alert physicians to advise appropriate investigation, as the majority of young-onset colorectal cancer patients develop painless bleeding 2 to 3 years before appearance of other symptoms.

Natural killer cells enhance the immune surveillance of cancer

Immune system [IS] is comprised of molecules, cells, tissues and organs involved in host defense mechanism from infectious agents or tumor cells. On crossing the cell barriers by these infectious agents, the defense mechanism is alerted by the immune system to respond against these invading microbes. Innate immune response [IIR] and acquired immune response [AIR] are working in parallel to control these invading microbes. IIR is composed of various types of phagocytes and lymphocytes, while AIR is comprised of T and B lymphocytes. All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer [NK] cells are playing an important role to respond to tumor by enhancing the expression of complementary domain [CD86] on dendritic cells [DCs] and production of IL-12. NK cells demolished tumor through perforin and granzyme, which are important for immune surveillance and death of tumor cells induced by cytokines such as tumor necrosis factor [TNF], Fas ligand [CD178], interferon-c [IFN-[gamma]] and IL-10. These cytokines have inhibited proliferation of tumor by inducing antiangiogenic factors and maintaining cross talk with other immune cells. Natural products like transfer factor plus, immune modulator mix, ascorbic acid, Ganoderma lucidum, Agaricus blazei teas, nitrogenated soy extract, Andrographis paniculata and several phytochemicals enhanced the efficiency of NK cells in controlling cancers. Further studies will unravel the impact of NK cells in cancer control and how NK efficiency can be further enhanced