Association of Vitamin A Deficiency with Cervical Squamous Intraepithelial Lesions in Human Immunodeficiency Virus–Infected Women

French, Audrey L.; Kirstein, Lynn M.; Massad, L. Stewart; Semba, Richard D.; Minkoff, Howard; Landesman, Sheldon; Palefsky, Joel M.; Young, Mary; Anastos, Kathryn; Cohen, Mardge H.

doi:10.1086/315816

Cited by 25 publications

(16 citation statements)

References 26 publications

(33 reference statements)

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“…This may provide a plausible explanation for the increased incidence and higher risk of cancer formation and development observed in individuals with VAD. Epidemiological studies have not only shown that an increased incidence of lung cancer has been observed in individuals with VAD, but have also pointed to an association between VAD and cancers arising in the uterine cervix, oral cavity and oropharynx (French et al, 2000). Similarly, ultraviolet irradiation induces a functional VAD state in skin that may contribute to skin carcinogenesis, suggesting an association between VAD and a high risk of some types of cancer (Wang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

2009

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Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis in animal models and elevated risk for a number of human cancers. Here, we found that CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, is highly expressed in 42% (27/65) of primary breast cancers. We also showed that enhanced expression of CYP26A1 suppresses cellular responses to anoikis and consequently promotes anchorage-independent growth. This transformed phenotype was sufficient to markedly increase tumorigenic and metastatic potential. Suppression of CYP26A1 significantly reversed the CYP26A1-mediated oncogenic characteristics, suggesting a direct link between intracellular RA status and tumorigenicity. Our observations provide strong evidence for oncogenic and cell survival properties of CYP26A1 in carcinogenesis, and suggest mechanisms whereby VAD might promote cancer development.

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Section: Discussionmentioning

confidence: 99%

Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

2009

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“…But, our focus was to assess the risk for morphological injury (SIL) and not specifically an HPV infection. While this may be a limitation to this study, French et al [10] measuring retinol concentrations with high-performance liquid chromatography demonstrated that the prevalence of DNA HPV was not different between women with low or normal levels of retinol.…”

Section: Discussionmentioning

confidence: 78%

“…Diet may be one important cofactor of squamous intraepithelial lesion (SIL), mainly HSIL and squamous carcinoma. There are studies in vitro and in vivo suggesting the relationship between vitamin A deficiency and neoplasia [10]. These data suggest that there may also be a concomitant shortage of this vitamin in the adult population.…”

Section: Introductionmentioning

confidence: 99%

The Risk of High-Grade Squamous Intraepithelial Lesions in Women with Low Serum Levels of Vitamin A

Eleutério¹,

Giraldo²,

Gonçalves³

et al. 2014

Gynecol Obstet Invest

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Background: The progression of the cervical squamous intraepithelial lesion (SIL) is associated with many cofactors, and nutritional aspects are gradually assuming an important role in understanding the physiopathogenesis. Objective: To assess the serum levels of retinol in women from a poor region of Brazil with a histological diagnosis of cervical high-grade SIL (HSIL). Methods: A cross-sectional study was conducted in 62 women aged 14-48 years who had a cervical biopsy and were treated at the Federal University of Ceara in Fortaleza, Brazil. Serum retinol levels were measured in peripheral blood by a spectrophotometry technique. Values were categorized as subnormal (<20 µg/dl) or normal (≥20 µg/dl). Multivariate logistic regression was used to determine the association between serum levels of retinol and HSIL for a confidence interval of 95%. Results: Twenty-six out of 62 women (42%) had a negative histopathological result for SIL and 36 (58%) were diagnosed with SIL (20 low SIL and 16 high SIL). The level of retinol was more frequently low in women with HSIL, but there was no statistical significance [p = 0.409, OR: 2.26 (0.33-15.59)]. Conclusion: There was no association between high SIL and low levels of retinol in peripheral blood.

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“…This hypothesis is based on a mechanistic link between VAD and increased risk for various types of cancer (8). Consistently, a number of published studies have identified that individuals with VAD accumulate DNA damage at a higher frequency, eventually resulting in increased risk and incidence of cancer (12,13). Conversely, there has been increased interest in the use of RA and synthetic derivatives (known as retinoids) in cancer therapy and dermatology.…”

Section: Discussionmentioning

confidence: 89%

Retinoic acid‑metabolizing enzyme cytochrome P450 26A1 promotes skin carcinogenesis induced by 7,12‑dimethylbenz[a]anthracene

Osanai

Takasawa

et al. 2018

Oncol Lett

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Abstract. Elevated expression of the retinoic acid-metabolizing enzyme cytochrome P450 26A1 (CYP26A1) has been demonstrated to have an oncogenic function in carcinogenesis. In order to address the oncogenic capacity of CYP26A1 in vivo, transgenic mice that ubiquitously overexpressed CYP26A1 driven by the cytomegalovirus promoter were generated in the present study. Since the growth of these animals was normal for ≤15 months and they presented no evident abnormalities, a two-stage skin carcinogenesis analysis was performed. In the CYP26A1 transgenic mice, papilloma formation was observed within 7 weeks after administration of the carcinogen 7,12-dimethylbenz[a] anthracene (DMBA). Development of papillomas in these animals was significantly accelerated when compared with that observed in the control mice following treatment with DMBA in combination with the chemical tumor promoter 12-O-tetradecanoylphorbol-13-acetate. In addition, constitutive expression of CYP26A1 increased the susceptibility of these mice to the generation of squamous cell carcinomas caused by treatment with the carcinogen alone. It is thus concluded that CYP26A1 expression promotes skin carcinogenesis initiated by DMBA.

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Association of Vitamin A Deficiency with Cervical Squamous Intraepithelial Lesions in Human Immunodeficiency Virus–Infected Women

Cited by 25 publications

References 26 publications

Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

The Risk of High-Grade Squamous Intraepithelial Lesions in Women with Low Serum Levels of Vitamin A

Retinoic acid‑metabolizing enzyme cytochrome P450 26A1 promotes skin carcinogenesis induced by 7,12‑dimethylbenz[a]anthracene

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