Prostate cancer is one of the most commonly diagnosed cancer in the Western world. The incidence rate of prostate cancer reported among Asians is much lower as compared to Americans (Yang et al., 2013[24]). In Pakistan it is the third frequent malignancy in males and the diagnostic and therapeutic facilities of such a prevalent cancer are limited in our country (Ahmad et al., 2009[2]). In order to understand the biology of prostate cancer and develop new interventions, complete analysis of different risk factors along with their comparison with genetics is essential (Hoffman, 2011[10]).

Epidemiological data suggested that age, smoking, dietary habits, genetics and many other factors may be involved in prostate cancer development. Age plays an important role in the development of prostate cancer and its incidence increases with the increased age. An abrupt increase in the prostate cancer cases was observed in the last two to three decades in Pakistan because of increased industrialization and urbanization (Mahmood et al., 2012[16]). Common symptoms for prostate cancer includes frequent urination, dysuria, hematuria, nocturia and difficulty in maintaining steady urine stream (Cramer et al., 2007[9]).

Glutathione S-transferases (GSTs) are detoxifying enzymes and play an important role in the detoxification of a number of exogenous and endogenous carcinogens by conjugation with glutathione (Agalliu et al., 2006[1]). Deletion of GSTM1 and GSTT1 genes leads to failure of the expression of GST proteins, which may cause reduced detoxification of potential carcinogens and lead to greater vulnerability to cancer (Spurdle et al., 2001[22]).

Recently, several studies have evaluated the association of GSTM1 and GSTT1 with prostate cancer but inconsistency is observed in the results (Albertsen et al., 2005[3]; Hu et al., 2013[11]; Yang et al., 2013[24]). However no specific data is available for Pakistani population regarding their genetic status. Therefore, current study is aimed to evaluate the xenobiotic metabolizing gene expression (GSTM1 and GSTT1) at DNA level and find out their correlation with progression of prostate cancer along with environmental risk factors.

This case control study was conducted over a period of 12 months and included 350 prostate cancer patients and 300 controls. Blood sample from already diagnosed and undergoing treatment prostate cancer patients were collected from Benazir Bhutto Shaheed Hospital, Rawalpindi, Shifa International Hospital, Urology department, Islamabad, Nuclear Medicine Oncology and Radiotherapy Institute, Islamabad and Institute of Nuclear Medicine and Oncology Lahore. Whereas control samples were collected from general population from Lahore, Rawalpindi and Islamabad.

Inclusion criteria for cases was histologically diagnosed and confirmed by oncologists as prostate cancer patients with Gleason scores 5-10 and for controls it was that the individuals should be cancer free normal at the time of sampling and they should not have any family history of cancer and PSA level was normal (PSA < 4 ng/dl). Epidemiological data was collected by a standard questionnaire. Study was approved from the ethical committees of university as well as hospitals. Informed consent was taken from controls and patients before collecting any type of information or sample. DNA was extracted from lymphocytes by using phenol chloroform method and GSTM1 and GSTT1 was analyzed by multiplex PCR (Masood et al., 2011[17]). PCR product was run on 2 % agarose gel and visualized in gel documentation system. Gels were read by two technicians blind folded to each others decision. Statistical analysis was performed by using SPSS software.

It was found that occurrence of prostate cancer increases many times with increased age as reported in populations of Africa, UK, America, Australia, India and Pakistan (Bhurgri et al., 2009[5]). No significant association of prostate cancer with occupation was found (Choubey et al., 2012[8]) whereas prostate cancer and smoking were found to be strongly associated in this study as well as in African, Americans and Chinese populations (Leitzmann and Rohrmann, 2012[15]; Islami et al., 2014[12]). Such cases were also reported where number of cigarettes smoked per day were significantly associated with onset and proliferation of prostatic carcinoma. Both environment and genetics were involved in prostate cancer development. Various environmental constituents weaken the immune system and played an important role in the proliferation of cancer. A study conducted in two different islands Guadeloupe and Martinique by Belpomme in 2009 revealed that development of prostate cancer was independent of change in mens life style (Belpomme et al., 2009[4]).

Glutathione S-transferases were the most commonly studied antioxidant enzymes which were involved in the detoxification of various carcinogens and reactive oxygen species. Any change in these enzymes caused the loss of complete enzymatic activity. Hence, individuals were at greater risk towards the development of prostatic carcinoma (Mo et al., 2009[19]).

No association was observed between GSTM1 deletion and prostate cancer. Similar results have frequently been reported in South Indian, Japanese, American and Africans populations (Caceres et al., 2005[6]). GSTT1 deletion was not associated with prostate cancer in the current study and in Asian, Caucasian, Korean, African and American men (Cai et al., 2014[7]). Dual null deletion of GSTM1 and GSTT1 were not associated with prostate cancer and similar results had been found in studies of African descent, Brazilian and Caucasians (Lavender et al., 2009[14]). Therefore, these two genes vary ethnically and geographically. Another meta-analysis showed no association of these two genes with the development of prostate cancer (Ntais et al., 2005[20]).

No significant association was found between the deletion of GSTM1 and prostate cancer among smokers. Similar kind of results were revealed among Asians, North Indians and Chileans (Mittal et al., 2004[18]; Caceres et al., 2005[6]; Silig et al., 2006[21]; Wei et al., 2012[23]).

GSTT1 deletion was also not associated with prostatic carcinoma among smokers. It was reported that GSTT1 deletion and prostate cancer were not associated among smokers in Turkish, Finnish and Indian populations (Kidd et al., 2003[13]; Mittal et al., 2004[18]; Silig et al., 2006[21]).

It was included that smoking, family history of cancer and GSTM1 deletion at stage IV are significant risk factors of prostate cancer. However, GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population.

All authors would like to thank the individuals and hospitals who participated in this research. Acknowledgement also goes to the University and Higher Education Commission of Pakistan for supporting this research.

All authors declare that there is no conflict of interests in this research. No particular grant or funding was received for the project.