Translating cancer 'omics' to improved outcomes.

The genomics era has yielded great advances in the understanding of cancer biology. At the same time, the immense complexity of the cancer genome has been revealed, as well as a striking heterogeneity at the whole-genome (or omics) level that exists between even histologically similar tumors. The vast accrual and public availability of multi-omics databases with associated clinical annotation including tumor histology, patient response, and outcome are a rich resource that has the potential to lead to rapid translation of high-throughput omics to improved overall survival. We focus on the unique advantages of a multidimensional approach to genomic analysis in this new high-throughput omics age and discuss the implications of the changing cancer demographic to translational omics research.

Cabbage and Sauerkraut Consumption in Adolescence and Adulthood and Breast Cancer Risk among US-Resident Polish Migrant Women.

BACKGROUND: Breast cancer (BC) incidence and mortality are lower in Poland than in the United States (US). However, Polish-born migrant women to US approach the higher BC mortality rates of US women. We evaluated the association between consumption of cabbage/sauerkraut foods and BC risk in Polish-born migrants to US. METHODS: We conducted a case-control study of BC among Polish-born migrants in Cook County and the Detroit Metropolitan Area. Cases (n = 131) were 20-79 years old with histological/cytological confirmation of invasive BC. Population-based controls (n = 284) were frequency matched to cases on age and residence. Food frequency questionnaires assessed diet during adulthood and age 12-13 years. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. Consumption of total, raw/short-cooked, and long-cooked cabbage/sauerkraut foods was categorized as low, medium, or high (frequency of servings/week). RESULTS: Higher consumption of total and raw/short-cooked cabbage/sauerkraut foods, during both adolescence and adulthood, was associated with a significantly lower BC risk. Consumption of long-cooked cabbage/sauerkraut foods was low and not significantly associated with risk. The multivariate OR for total cabbage/sauerkraut consumption, high vs. low (>4 vs. ≤2 servings/week) during adolescence was 0.36 (95% CI = 0.18-0.71, ptrend < 0.01) and 0.50 (95% CI = 0.23-1.06, ptrend = 0.08) during adulthood. For raw/short-cooked cabbage/sauerkraut (>3 vs. ≤1.5 servings/week), the ORs were 0.35 (95% CI = 0.16-0.72, ptrend < 0.01) during adolescence and 0.37 (95% CI = 0.17-0.78, ptrend < 0.01) during adulthood. For joint adolescent/adult consumption of raw/short-cooked cabbage/sauerkraut foods, (high, high) vs. (low, low), the OR was 0.23 (95% CI = 0.07-0.65). The significant association for high adolescent consumption of raw/short-cooked cabbage/sauerkraut foods and reduced BC risk was consistent across all levels of consumption in adulthood. CONCLUSION: Greater consumption of total and raw/short-cooked cabbage/sauerkraut foods either during adolescence or adulthood was associated with significantly reduced BC risk among Polish migrant women. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk.

An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species.

BACKGROUND: Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types. RESULTS: Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls. CONCLUSION: These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology.

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation.