Detection and Concentration of Plasma Aflatoxin Is Associated With Detection of Oncogenic Human Papillomavirus in Kenyan Women

Zhang, Jianjun; Orang’o, Omenge; Tonui, Philip; Tong, Yan; Maina, Titus; Kiptoo, Stephen; Muthoka, Katpen; Groopman, John D.; Smith, Joshua W.; Madeen, Erin; Ermel, Aaron; Loehrer, Patrick J.; Brown, Darron R.

doi:10.1093/ofid/ofz354

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…While exposure to certain carcinogens has declined with preventative education, other carcinogens cannot be completely avoided as they occur naturally or in the diet. Aflatoxins are mycotoxins produced by fungi which may contaminate a large portion of the world's food supply leading to cancer progression including hepatocellular carcinoma (HCC) ( Marchese et al, 2018 ; Xue et al, 2019 ; Zhang et al, 2019 ). Other natural carcinogens include minerals like cadmium, nickel or erionite, thorium, crystalline silica, ultraviolet light, or radon gases.…”

Section: Human Carcinogensmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

129

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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Section: Human Carcinogensmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

129

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“…However, given our current results and combined with the added cost, analysis time, sample consumption, and heterogeneity between HSA assays, it seems prudent to abandon the practice of normalizing HSA adducts to the total circulating HSA concentration when measuring any HSA adducts—not only AFB 1 -lys adducts—by isotope-dilution mass spectrometry in serum or plasma. As a result, we have initiated this shift within our own laboratory, recently showing that elevated raw AFB 1 -lys concentrations were significantly associated with the cervical detection of oncogenic strains of HPV in Kenyan women [ 39 ] and, separately, revealing seasonal, demographic, and behavioral predictors of aflatoxin exposure in 828 mother-child dyads from Bangladesh and Malawi [ 24 ]. Eschewing unnecessary and resource-consuming practices such as the HSA normalization of AFB 1 -lys adducts will allow for more efficient use of precious samples and research funds, while producing superior data.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Validity of Normalizing Aflatoxin B1-Lysine Albumin Adduct Biomarker Measurements to Total Serum Albumin Concentration across Multiple Human Population Studies

Smith

Álvarez

et al. 2022

Toxins

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The assessment of aflatoxin B1 (AFB1) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB1-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring of AFB1 exposure. To compare samples across different individuals and settings, the conventional practice has involved the normalization of raw AFB1-lysine adduct concentrations (e.g., pg/mL serum or plasma) to the total circulating HSA concentration (e.g., pg/mg HSA). It is hypothesized that this practice corrects for technical error, between-person variance in HSA synthesis or AFB1 metabolism, and other factors. However, the validity of this hypothesis has been largely unexamined by empirical analysis. The objective of this work was to test the concept that HSA normalization of AFB1-lysine adduct concentrations effectively adjusts for biological and technical variance and improves AFB1 internal dose estimates. Using data from AFB1-lysine and HSA measurements in 763 subjects, in combination with regression and Monte Carlo simulation techniques, we found that HSA accounts for essentially none of the between-person variance in HSA-normalized (R2 = 0.04) or raw AFB1-lysine measurements (R2 = 0.0001), and that HSA normalization of AFB1-lysine levels with empirical HSA values does not reduce measurement error any better than does the use of simulated data (n = 20,000). These findings were robust across diverse populations (Guatemala, China, Chile), AFB1 exposures (105 range), HSA assays (dye-binding and immunoassay), and disease states (healthy, gallstones, and gallbladder cancer). HSA normalization results in arithmetic transformation with the addition of technical error from the measurement of HSA. Combined with the added analysis time, cost, and sample consumption, these results suggest that it may be prudent to abandon the practice of normalizing adducts to HSA concentration when measuring any HSA adducts—not only AFB1-lys adducts—when using LCMS in serum/plasma.

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“…In addition, a longer duration of ART use was associated with significantly reduced risk of HR-HPV detection and persistence [ 36 ]. Lastly, exposure to dietary aflatoxin was significantly associated with detection of oncogenic HPV types [ 37 ] .…”

Section: The Consortium Version 1: “Hpv and Cervical Cancer In Kenyan...mentioning

confidence: 99%

The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS

et al. 2022

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The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGES The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer. Collaborations have been established between researchers in North America and East African countries for these studies. Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.

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Detection and Concentration of Plasma Aflatoxin Is Associated With Detection of Oncogenic Human Papillomavirus in Kenyan Women

Cited by 11 publications

References 46 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Assessing the Validity of Normalizing Aflatoxin B1-Lysine Albumin Adduct Biomarker Measurements to Total Serum Albumin Concentration across Multiple Human Population Studies

The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS

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