• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4513-4518
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• 2014

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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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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• v.13 no.7
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• pp.3305-3311
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• 2012

Background: The present study aimed to find the prognostic implications of two polymorphisms in TP53 (p.R72P, PIN3 Ins16bp) and one in CCR5 ($CCR5{\Delta}32$) in sporadic breast cancer patients. Methods: DNA samples of 80 breast cancer patients and 80 age and gender matched unrelated healthy control individuals from Punjab, North West India were analyzed. Results: For p.R72P, the genotype frequency was 13.8% (RR), 58.8% (RP), 27.5% (PP) in patients and 33.9% (RR), 40.0% (RP), 26.5% (PP) in controls. For PIN3 Ins16bp, the genotype frequencies were 53.75% (A1A1), 37.5% (A1A2), 8.75% (A2A2) in patients and 66.3% (A1A1), 31.3% (A1A2), 2.5% (A2A2) in controls. Only 4 (5%) breast cancer patients were heterozygous for $CCR5{\Delta}32$ deletion. Common RR-A1A1-WT/WT genotype was lower while RP-A1A2-WT/WT genotype was higher in patients as compared to controls. RP-A1A1-WT/WT genotype was significantly higher in patients as compared to control individuals (p = 0.008). Conclusion: Though a clear association of any particular genotype with sporadic breast cancer or stage was not apparent, the results of present study were suggestive that sporadic breast cancer patients with RR-A1A1-WT/WT genotype might have a better response to chemotherapy, thus improving their chances of survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.257-263
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• 2014

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4051-4055
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• 2015

The purpose of this study is to assess the effect of consanguinity on breast cancer incidence in Tunisia. We conducted a case-control study to evaluate the involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs according to consanguinity among 40 cases of familial breast cancer, 46 cases with sporadic breast cancer and 34 healthy controls. We showed significant difference in consanguinity rate between breast cancer patients versus healthy controls P=0.001. Distribution of homozygous BRCA1 haplotypes among healthy women versus breast cancer patients was significantly different; p=0.02. Parental consanguinity seems to protect against breast cancer in the Tunisian population.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.15-21
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• 2007

Hereditary syndromes cause approximately 5 to 10% of overall cancer cases. Cancer related with genetic syndromes are found elsewhere, including stomach, breast, colorectum, ovary, brain and so on. Because hereditary cancers are due to germline mutations, these patients have unique clinical features distinct from sporadic cancer. Generally these features include (i) early age-of onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent bilateral involvement in paired organs (iv) frequent association with other site tumors or characteristic clinical manifestation specific to each genetic syndrome. Due to these differences, the management strategy for patients with hereditary cancer is quite different from that for sporadic cancer. Additionally, there are important screening and surveillance implications for family members. Genetic counselling is prerequisite to these families for risk assessment by pedigree analysis, and guidance to clinical or genetic testing. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become important determining factor in clinical decisions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6871-6879
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• 2014

Background: The purpose of this study was to evaluate the potential association of five (p.P47S, p.R72P, PIN3 Ins16bp, p.R213R and r.13494g>a) polymorphisms of TP53 with the risk of developing breast cancer in North Indian Punjabi population. Methods: We screened DNA samples of 200 sporadic breast cancer patients (197 females and 3 males) and 200 unrelated healthy, gender and age matched individuals for the polymorphisms. Results: For the p.P47S polymorphism, we observed the PP genotype in 99.5% of the patients and PS genotype in only 1 patient. All the controls had the wild type PP genotype. The frequency of RR, RP and PP genotype of p.R72P was 23.5% vs 33.5%, 51.5% vs 45.5% and 25% vs 21% in patients and controls respectively. Heterozygous (RP) genotype was increased in breast cancer patients as compared to controls (51.5 vs 45.5%) and showed 1.61 fold significantly increased risk for breast cancer (OR=1.61, 95% CI, 1.01-2.58, p=0.04). In breast cancer patients the frequencies of A1A1, A1A2 and A2A2 genotypes of PIN3 Ins16bp polymorphism were 67%, 26% and 7% respectively whereas in controls the genotype frequencies were 68.5%, 27.5% and 4% respectively, with no significant difference. For p.R213R (c.639A>G), all individuals had homozygous wild type genotype. The frequencies of GG, GA and AA genotypes of TP53 r.13494g>a polymorphism were 62 vs 67.5%, 33 vs 28% and 5 vs 4.5% in patients and controls respectively, again without significant difference. We observed that RP-A1A1 genotype combination of p.R72P and PIN3 Ins16bp and RP-GG combination of p.R72P and r.13494g>a polymorphism showed significant risk of breast cancer (OR=1.65, 95%CI: 0.98-2.78, p=0.05; OR=1.72, 95%CI: 1.01-2.92, p=0.04). Conclusion: The results of present study indicated that among the five TP53 polymorphisms investigated, the p.R72P polymorphism, and the RP-A1A1 and RP-GG genotype combination contribute to breast cancer susceptibility in North Indians.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7955-7958
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• 2014

Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast cancer is on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and their interaction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistatic effects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onset breast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using $chi^2$-test with 95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648, but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotype and TP53 hetero genotype had protective effects against breast cancer, while the hetero allele of FGFR2 in combination with the minor genotype of TP53 was associated with a high risk. This study revealed an important crosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidates risk variants should be further evaluated in studies with a larger sample size.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7243-7248
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• 2015

Background: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. Materials and Methods: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. Results: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. Conclusions: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9973-9978
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• 2014

Background: Hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-$1{\alpha}$ may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-$1{\alpha}$ with the risk of breast cancer in North Indian sporadic breast cancer patients. Materials and Methods: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Results: The CC and CA genotype frequency of HIF-$1{\alpha}$ g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-$1{\alpha}$ g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. Conclusions: The three HIF-$1{\alpha}$ polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.