Genetic Polymorphisms of INS, INSR and IRS-1 Genes Are Not Associated with Polycystic Ovary Syndrome in Croatian Women

Obesity and insulin resistance is a common finding in patients with polycystic ovary syndrome (PCOS). Significant number of PCOS women experience insulin resistance that is irrespective of the degree of obesity suggesting possible genetic basis. Therefore, several polymorphisms of the genes encoding for the insulin (INS), insulin receptor (INSR) or insulin receptor substrates (IRS) involved in postreceptor signaling have been explored for their association with abnormal sensitivity to insulin in PCOS. The aim of the present study was to determine whether selected polymorphisms of INS, INSR and IRS-1 are associated with the development of PCOS as well as with increased insulin resistance in Croatian women with PCOS. The study enrolled 150 women with PCOS and 175 control women. The diagnosis of PCOS was based on Rotterdam consensus criteria. Each subject underwent an evaluation of body mass index (BMI), hirsutism, acne and menstrual cycle abnormalities as well as follicular stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, androstendione, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), fasting glucose and fasting insulin. Insulin resistance (IR) was quantified using the homeostatic model assessment of IR (HOMA-IR). Molecular analyses for the genetic polymorphisms were preformed. There was a significant difference in clinical and biochemical characteristics of the studied groups except for BMI and fasting glucose levels. No significant differences were observed in the genotype and allele distribution of the VNTR INS, C/T INSR, Gly792Arg IRS-1 polymorphisms between cases and controls. Moreover, no association was found between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and parameters of insulin resistance in PCOS patients. In conclusion, our data does not support an association between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and susceptibility to PCOS or insulin resistance in Croatian women with PCOS

<it>KRAS </it>rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

<p>Abstract</p> <p>Background</p> <p>A single nucleotide polymorphism located in the 3'-untranslated region of the <it>KRAS </it>oncogene (<it>KRAS </it>variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the <it>KRAS </it>variant with sporadic and familial breast cancer and breast tumor characteristics.</p> <p>Methods</p> <p>Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for <it>BRCA1/2 </it>mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the <it>KRAS </it>genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models.</p> <p>Results</p> <p>No evidence of association was observed between the <it>KRAS </it>variant and risk of sporadic and familial breast cancer - either among <it>BRCA </it>carriers or non-<it>BRCA </it>carriers. The <it>KRAS </it>variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users.</p> <p>Conclusion</p> <p>Our data do not support the hypothesis that the <it>KRAS </it>variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the <it>KRAS </it>variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.</p