Mainstreaming genetic counseling for BRCA testing into oncology clinics – Indian perspective

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%–65% cumulative lifetime risk of developing breast cancer and an 11%–39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years. In India, the prevalence of BRCA1/2 mutation varies from 2.9% to 38% among families with genetic predisposition toward hereditary cancers. With HBOC being linked to early-onset breast cancer and increased susceptibility to other cancers, early screening for BRCA mutations has become a pressing need. Though genetic counseling (GC) for BRCA mutation testing is common in most of the developed countries, India still faces several challenges in mainstreaming the same. Many barriers to effective GC for BRCA testing are unique to India. There is a dearth of trained geneticists which puts the pressure on oncologists to give GC for which they neither have the time or training. Presence of multiethnic/linguistic population acts as a major hindrance along the way toward development of robust predictive and effective GC models for BRCA testing. The current review discusses the need and benefits of GC in breast cancer prevention, through BRCA testing, from an Indian perspective. The functional framework of GC and the role of genetic counselors are discussed in detail. In addition, importance of GC training and role of a multidisciplinary team approach for mainstreaming pre- and post-BRCA test GC is highlighted.

Relationship between PTEN and gestational diabetes in Asian Indians womens

Gestational diabetes mellitus [GDM] is defined as glucose intolerance of variable severity with onset of first recognition during pregnancy. GDM occurs in at least 30% of women with a family history of T2DM/GDM, suggesting that some women are genetically predisposed to develop GDM. Phosphatase and tensin homolog [PTEN] on chromosome 10 is a tumor-suppressor gene. Studies have demonstrated that PTEN dysfunction affects the function of insulin. However, the relationship between GDM and PTEN has not been studied. The aim of the present study was to investigate the relationship between PTEN and GDM in Asian Indian women. The case-control study used PCR-RFLP analysis to assess the PTEN?9C/G polymorphism in 150 GDM cases and 150 controls [non-GDM]. No alleles or genotypes were detected at statistically significant frequencies. All subjects were normal, and no variants were detected in any of the pregnant women. In conclusion, PTEN has no role in GDM, consistent with previous studies

Polymorphic [CAG]n repeats in the androgen' receptor gene: a risk marker for endometriosis and uterine leiomyomas

Endometriosis and uterine leiomyomas are leading hormone responsive, benign uterine disordders responsible for high morbidity in women of reproductive age group. A polymorphic [CAG]n repeat length located in exon 1 of the androgen receptor [AR] gene has been proposed as a risk marker for both endometriosis and leiomyomas in some ethnic groups. The present study was carried out to assess the frequency of AR [CAG]n repeat polymorphism as a risk marker for endometriosis and uterine leiomyomas in Asian Indian women. DNA was isolated from peripheral blood samples of 331 subjects, which include 90 endometriosis cases, 140 cases of leiomyomas and 101 healthy age- and sex-matched controls. PCR was carried out to amplify exon 1 of the AR gene. All the PCR amplicons were analysed initially on 2% agarose gel electrophoresis, folllowed by bidirectional sequencing to calculate the number CAG repeats in individuals. The CAG repeat ranges detected in endometriosis cases were 4-33 [Mode-19] and in leiomyomas cases 5-34 [Mode-20], whereas in controls it was 5-34 [Mode-22]. A distinct variation was observed in the three groups at 14, 18, 19, 20 and 22 [CAG]n repeats, which were statistically analyzed using chi-square and odds ratio tests. 19 CAG repeats were found to be higher in endometriosis cases [19.09%] when compared with conttrols [9.04%], while 20 CAG repeats were higher in leiomyomas cases [14.02%] compared to controls [6.14%]. A statistically significant [P < 0.05] association was observed in 19 and 20 CAG repeats in endometriosis and leiomyomas, respectively. This is the first report from an Asian Indian population proposing that 19 and 20 CAG repeats of the AR gene are associated with endometriosis and leiomyoma and can be regarded as high-risk markers