In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.

Dibenzo[a,l]pyrene (DBP) is the most potent tumor initiating polycyclic aromatic hydrocarbon tested to date in rodent tumor models. To investigate how DBP adduct formation and removal might influence carcinogenesis, we have examined the effects of treatment of several nucleotide excision repair (NER)-proficient (NER(+)) and -deficient (NER(-)) cell lines with the carcinogenic metabolite (+/-)-anti-DBP-11,12-diol-13,14-epoxide (DBPDE). The treatment of NER(-) cells with (+/-)-anti-DBPDE for 0.5, 1, or 2 h yielded similar total adduct levels, indicating that adduct formation was essentially complete during a 2 h treatment period with no additional adducts produced after replacement of media. In all cell lines, treatment with (+/-)-anti-DBPDE generated five major and at least two minor adducts that were chromatographically identical to those formed by direct treatment of 3'-GMP and 3'-AMP with (+/-)-anti-DBPDE. When adduct levels were assessed in NER(-) cells, the number of adducts/10(9) nucleotides decreased over time, suggesting that DNA replication was ongoing, so we incorporated a normalization strategy based on DNA synthesis. This strategy indicated that DBPDE-DNA adduct levels in NER(-) cells are stable over time. After normalization for DNA synthesis in the NER(+) cells, our data indicated that three adducts showed biphasic repair kinetics. A faster rate of removal was observed during the first 6 h following DBPDE removal followed by a slower rate for up to 34 h. Importantly, two of the major guanine adducts were particularly refractory to removal in the NER(+) cells. Our results suggest that the extreme carcinogenicity of DBPDE may result from the ability of a substantial percentage of two structurally distinct DBPDE-DNA adducts to escape repair.

Inositol hexaphosphate (IP6) or phytic acid, contained in most mammalian cells, has been shown to have anticancer and anti-cell-proliferative effects in several experimental models of carcinogenesis. We investigated the effect of topical application of IP6 on 7,12-dimethylbenzanthracene (DMBA)-induced complete carcinogenesis and on selective critical events of proliferation, differentiation, or apoptosis after DMBA exposure. IP6 inhibited skin tumor development significantly in a dose-dependent manner. IP6 induced the DMBA-inhibited transglutaminase activity. DNA synthesis, as determined by [3H]thymidine incorporation, was suppressed by IP6 in a dose-dependent manner. IP6 also inhibited thymidine kinase enzyme, which is responsible for [3H]thymidine incorporation into DNA. Our results show that topical application of IP6 inhibits DMBA-induced mouse skin tumor development and that IP6 exerts its tumor inhibitory effect probably by modulating proliferation, differentiation, or apoptosis. It seems that IP6 is an effective and potential chemopreventive agent for management of skin tumorigenesis.

Non-insulin-dependent diabetes or type II diabetes is prevalent around the world. A high-fat diet and chronic inactivity are often responsible for this chronic ailment. However, it is suspected that a high level of stress can also exacerbate diabetes. High anxiety can result in the release of sympathetic hormones that can elevate both cortisol and glucose levels, decrease insulin release, or affect the sensitivity and resistant of the insulin hormone. We have analyzed three research articles to see how stress and anxiety can affect non-insulin-dependent diabetes. In the first article, we selected participants with type II diabetes and injected them with saline or norepinephrine. The results indicated that participants with norepinephrine had experienced a decrease in glucose disposal and reduction in insulin secretion rate. Our second article utilizes African-American adults with type II diabetes. We provide them with a survey to determine how stress, anxiety, and depression can affect adherence to lifestyle modifications such as exercise and eating a proper diet. We find that subjects with higher stress levels tend to have lower compliance with their lifestyle regimes. Our third article focuses on female participants and divides them into two categories which are high chronic stress (HCS) and low chronic stress (LCS). We use an MRI to observe their brain activity while they stare at a picture of high-caloric type food. Our results indicate that there are different responses in various brain structure activities between subjects with HCS and LCS group. With these analyses, it can improve on the way healthcare providers can consult with their patients who have exacerbated type II diabetes despite proper medication and lifestyle modification.