BRIP1/FANCJ Mutation Analysis in a Family with History of Male and Female Breast Cancer in India / 한국유방암학회지

Male breast cancer (MBC) is a rare and poorly studied disease that is a growing global health problem. Interestingly, both the molecular basis of MBC and its histological profile are often quite distinct from the far more prevalent female breast cancer, emphasizing the need for increased focus on MBC. Here, we present a case report of an MBC patient from India with a strong familial history of breast cancer. This patient was normal for BRCA1/2 and many other common breast cancer-associated genes. However, upon further analysis, the individual was found to possess two mutations in the DNA helicase and tumor suppressor gene BRIP1, including a silent mutation at residue 879 as well as a P919S variant. Other family members were also screened for these mutations. To the best of our knowledge, this is the first report of BRIP1 mutation in MBC in the Indian population.

Risk factors for congenital anomalies in high risk pregnant women: a large study from South India

Background: High Risk Pregnancy [HRP] is a condition where mother or developing fetus or both are at increased risk of complications during or after pregnancy and birth. There are no studies so far which have characterized congenital anomalies [CAs] in HRP women with different previous obstetric histories

Aim: The present study was aimed to determine the prevalence, types and distribution of various CAs and also to find out the exact risk factors for different obstetric histories

Subjects and methods: A total of 3301 HRP women [2011-2014] were enrolled. Diagnosis was made using 3D/4D ultrasound. Serum was analyzed for IgG and IgM against TORCH [Toxoplasma, Rubella, CMV and HSV] agents by ELISA. Eleven percent were pregnant women carrying fetuses with CAs in the present pregnancy, while remaining 89% were with bad obstetric history [BOH] and other medical and obstetric complications

Results: Eleven percent pregnant women were carrying fetuses with CAs in the present pregnancy. The major CAs observed were Central Nervous System [CNS] followed by renal anomalies. Maternal age [625 years, OR =1.42, p= 0.002], paternal age [<30 years, OR =1.51, p< 0.001], consanguinity [OR =1.39, p= 0.012] and primi gravida [OR= 3.40, p<0.001] were identified as risk factors for HRP women with fetal CAs in present pregnancy. Maternal age 625 years and paternal age <30 years conferred around 2-fold risk toward CAs in primi gravid women [p< 0.001] whereas consanguinity was associated with CAs in HRP women with BOH [OR= 1.95, p<0.018]. Toxoplasmosis played a significant role in pregnant women with CAs in present pregnancy with previous normal pregnancies [OR = 4.45, p= 0.009]

Conclusion: High prevalence of CAs was found in HRP women compared to general population. Low parental age contributed toward CAs in primi gravida women while consanguinity was found to be a predisposing factor for CAs in HRP with previous BOH. Toxoplasmosis conferred risk for CAs in HRP women with previous normal pregnancies

rare de novo balanced X; 1 translocation in an Indian female with primary amenorrhea

Translocations involving X chromosome and an autosome are rather rare due to associated infertility in men and subfertility in women. X chromosome translocations are frequently associated with primary or secondary amenorrhea. In this report, a case of primary amenorrhea with a de novo balanced reciprocal translocation was presented between chromosomes X and 1. A 24 year-old proposita with the complaint of primary amenorrhea was found to have hypoplastic uterus and streak gonads with a normal hormonal profile. Chromosomal analysis of the proband revealed a de novo translocation of 46, X, t[X; 1] [q21; p32] chromosomal constitution. Parental karyotypes of the proband showed normal karyotype. The observed translocation between chromosome X and 1 in the patient suggest either the disruption of a critical gene expression due to position effect or deletion of one or more essential genes in the disrupted long arm of the affected X chromosome. To the best of our knowledge, this is the first report from our ethnic group

Common SNP of IL-10 [-1082A/G] is associated with increased risk of Premenopausal Breast Cancer in South Indian Women

Background: Evading the immune destruction and angiogenesis has been the two hallmarks of cancer. Interleukin-10 [IL-10] is a cytokine with immune suppressing [pro-tumorigenic] and anti-angiogenic [anti-tumorigenic] properties, thus making the role of IL-10 in tumorigenesis enigmatic. Previous studies have suggested a critical role of IL10 altered expression in complex process of tumor-microenvironment, co-evolution and tumorigenesis

Objectives: Evaluating the role of IL10 [-1082A/G] gene promoter polymorphism in breast cancer patients from South India

Patients and Methods: A case-control study was conducted with a total of 285 individuals, these include 125 histologically confirmed breast cancer patients and 160 age and sex matched controls. Genotypes were determined by allele-specific polymerase chain reaction [AS-PCR], followed by agarose gel electrophoresis. Statistical analysis was done to test the significance of results obtained

Results: Statistical analysis revealed that AA genotype of the Il-10 -1082A/G polymorphism is significantly associated with breast cancer [AA vs. AG: x[2] = 14.46, P = 0.0001432, OR = 2.854, 95% CI = 1.68 - 4.849]. Up on stratifying subjects based on cancer stage, age at onset, menopausal status, AA genotype has associated with all the sub groups, except for post-menopausal women. There was no significant association which was observed with respected to hormonal status [ER, PR] and Her2/neu status

Conclusions: The present study suggests that IL-10 AA genotype as a risk factor in the etiology of breast cancer in the South Indian population

Role of tumor necrosis factor-alpha -308 G/A promoter polymorphism in gastric cancer

Gastric cancer [GC] is the fourth most common cancer and the second most common cause of cancer death world-wide after lung cancer. It is a multifactorial disease with the involvement of both genetic and environmental risk factors. Genetic variation in genes encoding cytokines and their receptors, determine the intensity of the inflammatory response, which may contribute to individual differences in severity of outcome of the disease. Tumor necrosis factor alpha [TNF- alpha] is a potent pro-inflammatory cytokine and acid inhibitor. A bi allelic G to A polymorphism at -308 upstream from the transcription initiation site of the promoter is associated with elevated TNF levels. The present study is aimed at evaluating the role of TNF- alpha-308 [G [rightwards arrow] A] gene polymorphism and susceptibility to GC. A case-control study was carried out in 114 GC patients and 229 healthy control subjects. TNF- alpha genotyping at position-308 [G [rightwards arrow] A] was carried out by amplification refractory mutation system-polymerase chain reaction [ARMS-PCR] method followed by agarose gel electrophoresis. The distribution of TNF- alpha genotypes at -308 [G [rightwards arrow] A] were GG 28.07%, GA 66.67% and AA 5.26% in GC patients and GG 33.19%, GA 55.89% and AA 10.92% in control subjects. The frequencies of alleles G and A were 0.614 and 0.386 in GC patients and 0.611 and 0.389 in control subjects respectively. The study showed no significant difference in the distribution of genotype and allelic frequencies between GC patients and control subject

Evaluation of interleukin-10 [G-1082A] promoter polymorphism in preeclampsia

Preeclampsia is a pregnancy-specific syndrome that may be life-threatening, especially to the fetus. Several causes have been reported that may have a possible role in the development of the disorder. Interleukin-10 affect maternal intravascular inflammation, as well as endothelial dysfunction. The aim of this study was to investigate the association between IL-10 G-1082A polymorphism and pre-eclampsia. A total of eighty-eight pregnant women with preeclampsia and 100 women with normal pregnancy attending the Gynecological unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the study. A standard amplification refractory mutation system [ARMS] PCR was carried out for genotyping IL-10 G-1082A promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups were compared with values predicted by Hardy-Weinberg equilibrium using chi[2] test. Odd ratios [OR] and their respective 95% confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. The frequencies of IL-10 G-1082A genotypes, GG, GA and AA, were 17.8%, 41.09% and 41.09% in women with preeclampsia and 25%, 28% and 47% in the controls respectively. There was no significant difference in the distribution of genotypes and alleles of IL-10 G-1082A between the two groups [Test power=0.66]. The present study suggests that the IL-10 G-1082A gene promoter polymorphism is not a major genetic regulator in the etiology of preeclampsia

Association of interleukin-10 promoter polymorphism [-1082 G/A] and gastric cancer in Andhra Pradesh population of South India

Gastric Cancer [GC] is one of the most commonly diagnosed malignancies. Genetic variation in genes encoding cytokines and their receptors, determine the intensity of the inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin-10 [IL-10] is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine inter-individual differences in IL-10 production. In the present study, we investigated the association between the IL-10 -1082 G/A polymorphism and the susceptibility to gastric cancer in a South Indian population from Andhra Pradesh. We genotyped 100 patients diagnosed with gastric cancer and 132 healthy control subjects for -1082G/A single nucleotide polymorphism by Amplification Refractory Mutation System-Polymerase Chain Reaction [ARMS-PCR] method followed by agarose gel electrophoresis. The distribution of IL-10 genotypes at -1082 G/A were GG 18%, GA 35% and AA 47% in gastric cancer patients and GG 31.82%, GA 37.88% and AA 30.3% in control subjects. The allelic frequencies of G and A were 0.355 and 0.645 in GC patients and 0.508 and 0.492 in control subjects respectively. The IL-10 -1082 A allele was associated with risk of gastric cancer [OR=1.873, 95%CI-1.285-2.73and P= 0.001048**]. Our study indicates that allele A of IL-10-1082 G/A polymorphism may be considered as one of the important risk factor in the etiology of gastric cancer