Metabolic profile predicts incident cancer: A large-scale population study in the UK Biobank.

BACKGROUND AND AIMS: Analyses to predict the risk of cancer typically focus on single biomarkers, which do not capture their complex interrelations. We hypothesized that the use of metabolic profiles may provide new insights into cancer prediction. METHODS: We used information from 290,888 UK Biobank participants aged 37 to 73 years at baseline. Metabolic subgroups were defined based on clustering of biochemical data using an artificial neural network approach and examined for their association with incident cancers identified through linkage to cancer registry. In addition, we evaluated associations between 38 individual biomarkers and cancer risk. RESULTS: In total, 21,973 individuals developed cancer during the follow-up (median 3.87 years, interquartile range [IQR] = 2.03-5.58). Compared to the metabolically favorable subgroup (IV), subgroup III (defined as "high BMI, C-reactive protein & cystatin C") was associated with a higher risk of obesity-related cancers (hazard ratio [HR] = 1.26, 95 % CI = 1.21 to 1.32) and hematologic-malignancies (e.g., lymphoid leukemia: HR = 1.83, 95%CI = 1.44 to 2.33). Subgroup II ("high triglycerides & liver enzymes") was strongly associated with liver cancer risk (HR = 5.70, 95%CI = 3.57 to 9.11). Analysis of individual biomarkers showed a positive association between testosterone and greater risks of hormone-sensitive cancers (HR per SD higher = 1.32, 95%CI = 1.23 to 1.44), and liver cancer (HR = 2.49, 95%CI =1.47 to 4.24). Many liver tests were individually associated with a greater risk of liver cancer with the strongest association observed for gamma-glutamyl transferase (HR = 2.40, 95%CI = 2.19 to 2.65). CONCLUSIONS: Metabolic profile in middle-to-older age can predict cancer incidence, in particular risk of obesity-related cancer, hematologic malignancies, and liver cancer. Elevated values from liver tests are strong predictors for later risk of liver cancer.

Genomic Profiling of the Steroidogenic Acute Regulatory Protein in Breast Cancer: In Silico Assessments and a Mechanistic Perspective.

Cancer is a multifactorial condition with aberrant growth of cells. A substantial number of cancers, breast in particular, are hormone sensitive and evolve due to malfunction in the steroidogenic machinery. Breast cancer, one of the most prevalent form of cancers in women, is primarily stimulated by estrogens. Steroid hormones are made from cholesterol, and regulation of steroid/estrogen biosynthesis is essentially influenced by the steroidogenic acute regulatory (StAR) protein. Although the impact of StAR in breast cancer remains a mystery, we recently reported that StAR protein is abundantly expressed in hormone sensitive breast cancer, but not in its non-cancerous counterpart. Herein, we analyzed genomic profiles, hormone receptor expression, mutation, and survival for StAR and steroidogenic enzyme genes in a variety of hormone sensitive cancers. These profiles were specifically assessed in breast cancer, exploiting The Cancer Genome Atlas (TCGA) datasets. Whereas StAR and key steroidogenic enzyme genes evaluated (CYP11A1, HSD3B, CYP17A1, CYP19A1, and HSD17B) were altered to varying levels in these hormone responsive cancers, amplification of the StAR gene was correlated with poor overall survival of patients afflicted with breast cancer. Amplification of the StAR gene and its correlation to survival was also verified in a number of breast cancer studies. Additionally, TCGA breast cancer tumors associated with aberrant high expression of StAR mRNA were found to be an unfavorable risk factor for survival of patients with breast cancer. Further analyses of tumors, nodal status, and metastases of breast cancer tumors expressing StAR mRNA displayed cancer deaths in stage specific manners. The majority of these tumors were found to express estrogen and progesterone receptors, signifying a link between StAR and luminal subtype breast cancer. Collectively, analyses of genomic and molecular profiles of key steroidogenic factors provide novel insights that StAR plays an important role in the biologic behavior and/or pathogenesis of hormone sensitive breast cancer.

A golden anniversary: highlights of the 50th annual meeting of the American Society of Clinical Oncology.

The 50th Annual Meeting of the American Society of Clinical Oncology showed a shift in the culture of cancer research, moving towards multidisciplinary, integrated, and patient-centric work. Hormone-sensitive cancers were particularly highlighted at this meeting, and impressive strides were made in the previously underserved areas of the lung and thyroid cancer. Interestingly, immunotherapy was one of the strongest themes to emerge.