Apolipoproteins, lipids and risk of cancer

Borgquist, Signe; Butt, Talha; Almgren, Peter; Shiffman, Dov; Stocks, Tanja; Orho‐Melander, Marju; Manjer, Jonas; Melander, Olle

doi:10.1002/ijc.30013

Cited by 174 publications

(163 citation statements)

References 47 publications

(92 reference statements)

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“…However, studies have shown a directly proportional relationship between ApoA‐1 levels and BC risk in women who did not undergo hormone‐replacement therapy . In addition, the ratio of apolipoprotein B (ApoB)/ApoA‐1 was found to be directly associated with BC risk . More research is clearly needed to establish a clear link between Apo‐A1 levels and BC.…”

Section: Rationale For Targeting Cholesterol For Treatment Of Cancermentioning

confidence: 99%

Targeting cellular cholesterol for anticancer therapy

Saha

Thomas

et al. 2019

The FEBS Journal

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Cholesterol dyshomeostasis in cancer cells leads to intracellular cholesterol accumulation, which imparts drug resistance and allows these cells to evade apoptotic signalling processes and maintain continuous cell division and proliferation. Therefore, cholesterol lowering in cancer cells has been envisaged as a potential anticancer strategy. In this direction, two therapeutic strategies have been proposed: (a) to inhibit the biosynthesis of cholesterol in the cells and (b) to deplete excess cholesterol from cancer cells. In the first phase of this review, we collate the cancer signalling pathways (particularly in breast cancer) that are perturbed by cholesterol dyshomeostasis and highlight recent drug discovery efforts to develop cholesterol‐lowering compounds, some of which are currently under clinical trials. In the second phase, based on the analysis of the available scientific evidence, we conceptualize and argue that the depletion of excess cholesterol could sensitize cancer cells to available therapeutics and may also help to alleviate cancer drug resistance.

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Section: Rationale For Targeting Cholesterol For Treatment Of Cancermentioning

confidence: 99%

Targeting cellular cholesterol for anticancer therapy

Saha

Thomas

et al. 2019

The FEBS Journal

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“…Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk234. However, the relationship between apolipoprotein (apo) A-I levels and breast cancer risk is not clear, as results of published studies are contradictory56.…”

mentioning

confidence: 99%

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Cedó

García-León

Baila-Rueda

et al. 2016

Sci Rep

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Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

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“…Five prospective cohort studies comprising 487 035 women and at least 15 163 cases were included in the review. A subset of 59 541 participants had LDL and apoB measured at baseline (Table ).…”

Section: Search Strategymentioning

confidence: 99%

“…For the secondary question, all studies evaluated LDL and apoB levels to compare BC risk as follows: Quartiles or cut‐off values Quartiles only Highest vs . lowest levels of exposure (dichotomized according to medical cut‐offs) …”

Section: Search Strategymentioning

confidence: 99%