• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5625-5629
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• 2013

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1599-1603
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• 2012

Objectives: Since methylenetetrahydrofolate reductase (MTHFR) maintains the balance of circulating folate and methionine and blocks the formation of homocysteine, its regulation in relation to different cancers has extensively been studied in different populations. However, information on Pakistani breast cancer patients is lacking. The MTHFR gene has two most common mutations that are single nucleotide additions which result in change of amino acids C677T to Ala222val and A1298C to Glu429Ala. Methodology: 110 sporadic breast patients with no prior family history of cancer or any other type of genetic disorders along with 110 normal individuals were screened for mutations in exons 1 to exon 9 using single strand conformational polymorphism, RFLP and sequencing analyzer. Results: The p values for the 677CC, 677CT, and 677TT genotypes were 0.223, 0.006, and 0.077, respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 0.555, 0.009, and 0.003, respectively. Conclusions: We found an overall a significant, weak inverse association between breast cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR polymorphism might be population specific in sporadic breast cancer affected patients but many other factors need to be excluded before making final conclusions including folate intake, population and disease heterogeneity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6339-6342
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• 2014

Background: The incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer <30 years of age and compare it with their older counterparts in the Pakistani population. Materials and Methods: A retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged ${\leq}30years$ and Group 2 aged >30years. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test. Results: There were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007). Conclusions: Early onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3973-3980
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• 2014

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

• Molecules and Cells
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• 제25권2호
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• pp.301-304
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• 2008

Microsatellites, short tandem repeats, are useful markers for genetic analysis because of their high frequency of occurrence over the genome, high information content due to variable repeat lengths, and ease of typing. To establish a panel of microsatellite markers useful for genetic studies of the Korean population, the allele frequencies and heterozygosities of 207 microsatellite markers in 119 unrelated Korean, Indian and Pakistani individuals were compared. The average heterozygosity of the Korean population was 0.71, similar to that of the Indian and Pakistani populations. More than 80% of the markers showed heterozygosity of over 0.6 and were valuable as genetic markers for genome-wide screening for disease susceptibility loci in these populations. To identify the allelic distributions of the multilocus genetic data from these microsatellite markers, the population structures were assessed by clustering. These markers supported, with the most probability, three clustering groups corresponding to the three geographical populations. When we assumed only two hypothetical clusters (K), the Korean population was separate from the others, suggesting a relatively deep divergence of the Korean population. The present 207 microsatellite markers appear to reflect the historical and geographical origins of the different populations as well as displaying a similar degree of variation to that seen in previously published genetic data. Thus, these markers will be useful as a reference for human genetic studies on Asians.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.10009-10013
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• 2014

Background: Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic research recently. Association studies between different types of cancers including prostate cancer (PCa) and VDR gene polymorphism have also been conducted. The objective of this study was to find possible associations between PCa and VDR gene polymorphisms in the Pakistani population. Materials and Methods: A total of 162 subjects, including prostate cancer patients and controls, were genotyped for Apa I, Taq I and Fok I polymorphisms in the VDR gene using allele specific PCR, PCR-RFLP and direct DNA sequencing. Allelic frequencies were tested for Hardy-Weinberg equilibrium and associations between the genetic markers and PCa were calculated using logistic regression. Results: Apa I CC genotype was found to have strongest association with PCa risk, and "A" genotype was found to have protective effect. Fok I and Taq I did not have appreciable levels of association with PCa, although Taq I "TC" heterozygotes seemed to have some protective effect. Similarly the "C" allele of Fok I also seemed to have protective effect. Conclusions: To our knowledge, this is the first report showing association between VDR gene polymorphisms and PCa in Pakistan. Our findings may be somewhat skewed because of small sample size and tendency of consanguineous marriages in Pakistani society; nevertheless, it shows the trend of association and protective effects of certain VDR gene polymorphisms against PCa.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.277-280
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• 2014

Background: Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population. Materials and Methods: A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance. Results: The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non-seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2). Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.183-188
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• 2013

Background: Breast cancer (BC), the most common female cancer in Pakistan, is associated with a very high mortality. However, the roles of individual risk factors for BC among Pakistani women are still controversial. To assess potential risk factors for BC, a matched case-control study was conducted in two tertiary care hospitals of Karachi, Pakistan. Materials and Methods: The study population included 297 pathologically confirmed incident cases of BC patients diagnosed between January 2009 and December 2010. 586 controls without any history of BC were matched on hospital and ${\pm}5$ years of ages. Results: Positive family history of BC (MOR=1.72; 95%CI: 1.10, 2.80 for first degree vs. none), single marital status (MOR=1.55; 95%CI: 1.10, 2.39 for single/divorced/widowed women vs. married women), older age at menopause (MOR=3.92; 95%CI: 2.52, 6.18 for menopausal women aged below 45 years, MOR=6.42; 95%CI: 3.47, 11.98 for menopausal women above 45 years of age compared with premenopausal women) conferred an increased risk of BC for women. Increasing parity decreased the risk of BC (MOR=0.90; 95%CI: 0.85, 0.97 for each live birth). Intake of Vitamin D supplements (MOR=0.30; 95%CI: 0.12, 0.81 for ${\leq}3$ years and MOR=0.27; 95%CI: 0.13, 0.56 for >3 years) was protective compared to non-users of Vitamin D. Conclusions: This study confirmed only few of the recognized risk factors in Pakistani women. The protective effect of Vitamin D is important from public health perspective and needs to be further explored through a randomized controlled trial.

• BMB Reports
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• 제37권5호
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• pp.552-555
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• 2004

Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n=211) and normotensive (n=108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group ($\chi^2$ = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F=0.672; P=0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged $\leq$ 40 years suggests that ACE has a role in early onset essential hypertension in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10237-10240
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• 2015

Background: Prostate cancer is the third most commonly diagnosed cancer among males in Pakistan but very little is known about risk factors among the Pakistani population. Therefore a hospital-based, case-control study was carried out in Faisalabad to identify potential risk factors. Materials and Methods: This study was based on 140 prostate cancer cases and 280 normal controls. Logistic regression was used to estimate odds ratios and 95% confidence intervals for odds ratios to assess the relationship between prostate cancer and different risk factors. Results: Family history of prostate cancer, age, smoking, obesity, consumption of red meat and frequent use of fat items significantly increased the prostate cancer risk (odds ratios and 95% confidence intervals of: 7.32; 1.79-29.8; 16.9, 5.60-50.8; 2.47, 1.17-5.18; 5.79, 2.66-12.6; 2.71, 1.07-6.91; and 3.39, 1.47-7.83, respectively. On the other hand, more consumption of fruit, fluid intake and better lifestyle (physical activity) significantly reduced the risk of developing prostate cancer with odd ratios and corresponding 95% confidence intervals of: 0.27, 0.11-0.61; 0.05, 0.02-0.12; and 0.28, 0.13-0.58. Conclusions: The results of the present study suggested that age, family history of prostate cancer, smoking, obesity, fluid intake, frequent use of fat items, consumption of fruits and better lifestyle might be associated with prostate cancer among Pakistani males.