Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study

Slattery, Martha L.; Lundgreen, Abbie; Hines, Lisa M.; Wolff, Roger K.; Torres-Mejia, G.; Baumgartner, Kathy N.; John, Esther M.

doi:10.1016/j.canep.2015.08.012

Cited by 20 publications

(23 citation statements)

References 48 publications

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“…Recently, some investigations found that POMC expression are significantly associated with docetaxel‐induced anorexia, DNA methylation, and morbidity risk in breast cancer . Previously, Stovold et al found that POMC expression predicts poor survival and liver metastases in patients with small‐cell lung cancer .…”

Section: Discussionmentioning

confidence: 99%

POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells

et al. 2017

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The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties. We then deciphered the intrinsic mechanism using analyses of mRNA expression array profiles. It has been determined that pro-opiomelanocortin (POMC) is closely related with protein phosphorylation mediated by G-protein-coupled estrogen receptor (GPER) in BCSC. Following, knockdown of POMC inhibits properties of mammosphere formation, CD44 CD24 population, CD44 expression, and clonogenicity ability in BCSC. We found that inhibition of POMC attenuates phosphorylation of AKT2 and GSK3β in BCSC. Further in vivo investigations demonstrated that POMC interference regulates proliferation of BCSC-bearing tumors. Combination of the clinical results that POMC positive expression is frequently upregulated in human breast cancer and POMC positivity correlated with a poor prognosis, POMC is a potential therapeutic target for BCSC. In conclusion, we have successfully established two long-term-cultured BCSC from clinical specimens. We further indicated that POMC acts as a potential therapeutic target and prognostic marker for future treatment of BCSC.

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Section: Discussionmentioning

confidence: 99%

POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells

et al. 2017

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“…Multiple candidate gene studies have reported heterogeneity in associations by IA ancestry [ 29 – 32 ]. A GWAS study of BC in Latinas found a protective variant near the ESR1 gene that is only observed in women that have IA ancestry.…”

Section: Breast Cancermentioning

confidence: 99%

Variability in Cancer Risk and Outcomes Within US Latinos by National Origin and Genetic Ancestry

et al. 2016

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Latinos have lower rates for most common cancer sites and higher rates of some less common cancers (gallbladder, liver, gastric, and cervical) than other ethnic/racial groups. Latinos are a highly heterogeneous population with diverse national origins, unique genetic admixture patterns, and wide spectrum of socio-demographic characteristics. Across the major cancers (breast, colorectal, prostate, lung, and liver) US-born Latinos have higher incidence and worse survival than foreign-born, and those with low-socioeconomic status have the lowest incidence. Puerto Rican and Cuban Latinos have higher incidence rates than Mexican Latinos. We have identified the following themes as understudied and critical to reduce the cancer burden among US Latinos: (1) etiological studies considering key sources of heterogeneity, (2) culturally sensitive cancer prevention strategies, (3) description of the molecular tumor landscape to guide treatments and improve outcomes, and (4) development of prediction models of disease risk and outcomes accounting for heterogeneity of Latinos.

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“…These genes were selected because of their association with energy homeostasis and cancer and/or obesity. We evaluate associations by genetic ancestry, given differences in risk associated with these genes by Native American (NA) ancestry (15). Additionally, NA ancestry has been shown to be an important determinate of breast cancer risk among population of mixed Caucasian and NA ancestry, with women with greater NA ancestry having lower incidence of breast cancer than women of European ancestry (16, 17) We evaluate the modifying effects of body mass index (BMI) on survival given the relationship between these genes and BMI and breast cancer (15, 18-20).…”

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confidence: 99%

Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study

Pellatt

Lundgreen

Wolff

et al. 2015

Cancer Causes Control

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Purpose The leptin-signaling pathway and other genes involved with energy homeostasis (EH), have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk. Methods We evaluated associations between 10 energy homeostasis genes and survival among 1186 non-Hispanic white (NHW) and 1155 Hispanic/Native American women diagnosed with breast cancer. Percent Native American (NA) ancestry was determined from 104 Ancestry Informative Markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance. Results The overall EH pathway was marginally significant for all-cause mortality among women with low NA ancestry (PARTP = 0.057). Within the pathway, ghrelin (GHRL) and leptin receptor (LEPR) were significantly associated with all-cause mortality (PARTP = 0.035 and 0.007, respectively). The EH pathway was significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.038). Three genes, cholecystokinin (CCK), GHRL, and LEPR were significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.046, 0.015, and 0.046, respectively) while neuropeptide Y (NPY) was significantly associated with breast cancer-specific mortality among women with higher NA ancestry (PARTP = 0.038). BMI did not modify these associations. Conclusions Our data support our hypothesis that certain EH genes influence survival after diagnosis with breast cancer; associations appear to be most important among women with low NA ancestry.

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Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study

Cited by 20 publications

References 48 publications

POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells

POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells

Variability in Cancer Risk and Outcomes Within US Latinos by National Origin and Genetic Ancestry

Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study

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