Obesity, weight gain, and ovarian cancer risk in African American women

Bandera, Elisa V.; Qin, Bo; Moorman, Patricia G.; Alberg, Anthony J.; Barnholtz‐Sloan, Jill S.; Bondy, Melissa L.; Coté, Michele L.; Funkhouser, Ellen; Peters, Edward S.; Schwartz, Ann G.; Terry, Paul; Schildkraut, Joellen M.

doi:10.1002/ijc.30115

Cited by 28 publications

(23 citation statements)

References 40 publications

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“…Overall, these data suggest that insulin is an important extracellular signal that could modulate DHCR24 expression via STAT3 to promote cell metastasis and progestin resistance in EC. Hyperinsulinemia in insulin resistance is one of the proposed mechanisms that explains the obesity-cancer link and has a detrimental effect on survival in cancer73132. Understanding the insulin signaling pathway involved in cell metastasis and progestin resistance will be critical for the development of new intervention strategies to prevent or treat EC associated with obesity.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Dai

Zhu

Liu

et al. 2017

Sci Rep

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3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.

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Section: Discussionmentioning

confidence: 99%

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Dai

Zhu

Liu

et al. 2017

Sci Rep

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“…African American women and Hispanic women have been shown to have a higher rate of obesity and have a higher body mass index (BMI) 18. A large prospective study demonstrated that the risk of death from ovarian cancer was higher in women with a BMI of 35–40 kg/m 2 when compared with those with a BMI of 18.5–24.9 kg/m 2 19 20. We thought this would correlate with Hispanic women having poorer outcomes; however, this study shows that instead they had shorter length of stay and a lower number of ‘deceased’ status at last contact.…”

Section: Discussionmentioning

confidence: 68%

African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type

Whitmore

Sheeder

Guntupalli

2020

Int J Gynecol Cancer

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ObjectiveThere has been an increase in the use of neoadjuvant chemotherapy in recent years. Our objective was to determine if African American women are more likely to receive neoadjuvant chemotherapy than primary debulking surgery, when compared to their Caucasian counterparts, and the impact of such an approach on oncologic outcomes.MethodsA retrospective cohort study was performed using the National Cancer Database (NCDB). Women aged 18–90 years, diagnosed with stage IIIC or IV epithelial ovarian cancer between January 2010 through December 2014 were included. Women with unknown treatment or treatments outside of neoadjuvant chemotherapy or primary debulking surgery were excluded. Only women of Caucasian, African American, or Hispanic origin who received either neoadjuvant chemotherapy or primary debulking surgery were included; all other races were excluded. Descriptive statistics were computed, and continuous variables were assessed for normality. Groups were compared using ANOVA or non-parametric medians tests for continuous variables, and chi-squared tests were used for dichotomous or categorical variables. Logistic regression was used to identify predictors of treatment. A p value of 0.05 was considered statistically significant.ResultsA total of 19 838 women with stage IIIC and IV epithelial ovarian cancer met the inclusion criteria. A total of 14 988 (75.6%) were treated with primary debulking surgery, while 4850 women (24.4%) were treated with neoadjuvant chemotherapy. Of those treated with neoadjuvant chemotherapy, 24.5% were white, 27.0% were African American, and 22.1% were Hispanic (p=0.005), and when adjusted for confounders, being African American was a predictor of receiving neoadjuvant chemotherapy (adjusted odds ratio (aOR) 1.29, 95% CI 1.10 to 1.51). Ninety-day mortality rates were higher in African American women compared with Caucasian and Hispanic women (2.9% vs 2.0% vs 1.6%, p=0.013). There were no differences in 30-day mortality, 90-day mortality, or status at last contact in African American women, when comparing neoadjuvant chemotherapy and primary debulking surgery. In Caucasian women, outcomes were worse in women receiving neoadjuvant chemotherapy.ConclusionsCompared to other races, African American women with advanced ovarian cancer are more likely to receive neoadjuvant chemotherapy than primary debulking surgery and had a higher 90-day mortality rate. In African American women there was no difference in outcomes based on treatment type.

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“…Übergewicht und Fettleibigkeit erhöhen das Risiko für das Auftreten eines Ovarialkarzinoms [20,21,43,[46][47][48]…”

Section: Antihormontherapie Als Medikamentöse Präventive Maßnahmeunclassified

Primäre Prävention – Mamma- und Genitalkarzinome

et al. 2019

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ZusammenfassungIn den letzten Jahren haben sich Diagnostik und Therapie im Bereich der gynäkologischen Onkologie und Senologie stetig weiterentwickelt. Dennoch ist das Versterben an einer Krebserkrankung in den hoch entwickelten Ländern eine der häufigsten Todesursachen der Frau 1. Maßnahmen zur Primärprävention sind daher von hoher Bedeutung, um die Morbidität und Mortalität von Krebserkrankungen zu senken.

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Obesity, weight gain, and ovarian cancer risk in African American women

Cited by 28 publications

References 40 publications

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type

Primäre Prävention – Mamma- und Genitalkarzinome

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