Laron syndrome - A historical perspective.

Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a typical phenotype that includes dwarfism, obesity and hypogenitalism. The disease is caused by deletions or mutations of the GH-receptor gene, causing high serum GH and low IGF-I serum levels. We studied 75 patients from childhood to adult age. After early hypoglycemia due to the progressive obesity, patients tend to develop glucose intolerance and diabetes. The treatment is by recombinant IGF-I, which improves the height and restores some of the metabolic parameters. An unexpected finding was that patients homozygous for GH-R defects are protected from malignancy lifelong, not so heterozygotes or double heterozygote subjects. We estimate that there are at least 500 patients worldwide, unfortunately only few treated.

Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs).

Although great progress has been achieved during the last decades, the clinical management of organ transplant recipients (OTRs) remains a challenge. OTRs need in general lifelong immunosuppressive therapy that is associated with an increased risk to develop skin cancer and with an unfavorable clinical outcome of these malignancies. Skin cancer prevention measures, including regular full-body examinations, are therefore necessary in OTRs to detect and treat suspicious lesions at an early stage. The frequency of aftercare depends on the individual risk factors of the patient. Patients should apply consistent sun protection with sunscreens and clothing, as well as a monthly self-examination. On the other hand, the need of UVR avoidance increases the risk of vitamin D deficiency, which itself is associated with an increased risk for many diseases, including malignancies. OTRs should therefore be monitored for 25(OH)D status and/or should take vitamin D supplements. It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist, is needed to ensure the best care for the OTRs.

A tumor profile in Patau syndrome (trisomy 13).

Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome.

A tumor profile in Edwards syndrome (trisomy 18).

Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc.

Colorectal cancer prevention by an optimized colonoscopy protocol in routine practice.

We conducted a retrospective cohort study to investigate the colorectal cancer (CRC) incidence and mortality prevention achievable in clinical practice with an optimized colonoscopy protocol targeting near-complete polyp clearance. The protocol consisted of: (i) telephonic reinforcement of bowel preparation instructions; (ii) active inspection for polyps throughout insertion and circumferential withdrawal; and (iii) timely updating of the protocol and documentation to incorporate the latest guidelines. Of 17,312 patients provided screening colonoscopies by 59 endoscopists in South Carolina, USA from September 2001 through December 2008, 997 were excluded using accepted exclusion criteria. Data on 16,315 patients were merged with the South Carolina Central Cancer Registry and Vital Records Registry data from January 1996 to December 2009 to identify incident CRC cases and deaths, incident lung cancers and brain cancer deaths (comparison control cancers). The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) relative to South Carolina and US SEER-18 population rates were calculated. Over 78,375 person-years of observation, 18 patients developed CRC versus 104.11 expected for an SIR of 0.17, or 83% CRC protection, the rates being 68% and 91%, respectively among the adenoma- and adenoma-free subgroups (all p < 0.001). Restricting the cohort to ensure minimum 5-year follow-up (mean follow-up 6.64 years) did not change the results. The CRC mortality reduction was 89% (p < 0.001; four CRC deaths vs. 35.95 expected). The lung cancer SIR was 0.96 (p = 0.67), and brain cancer SMR was 0.92 (p = 0.35). Over 80% reduction in CRC incidence and mortality is achievable in routine practice by implementing key colonoscopy principles targeting near-complete polyp clearance.

Endogenous p53 inhibitor TIRR dissociates systemic metabolic health from oncogenic activity.

It is unclear whether metabolic health corresponds to reduced oncogenesis or vice versa. We study Tudor-interacting repair regulator (TIRR), an inhibitor of p53 binding protein 1 (53BP1)-mediated p53 activation, and the physiological consequences of enhancing tumor suppressor activity. Deleting TIRR selectively activates p53, significantly protecting against cancer but leading to a systemic metabolic imbalance in mice. TIRR-deficient mice are overweight and insulin resistant, even under normal chow diet. Similarly, reduced TIRR expression in human adipose tissue correlates with higher BMI and insulin resistance. Despite the metabolic challenges, TIRR loss improves p53 heterozygous (p53HET) mouse survival and correlates with enhanced progression-free survival in patients with various p53HET carcinomas. Finally, TIRR's oncoprotective and metabolic effects are dependent on p53 and lost upon p53 deletion in TIRR-deficient mice, with glucose homeostasis and orexigenesis being primarily regulated by TIRR expression in the adipose tissue and the CNS, respectively, as evidenced by tissue-specific models. In summary, TIRR deletion provides a paradigm of metabolic deregulation accompanied by reduced oncogenesis.

Cancer in growth hormone excess and growth hormone deficit.

The relationship between growth hormone (GH) excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and insulin-like growth facto-I deficits exist are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated with increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated with augmented cancer risk. In a study performed in Ecuador, it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in the benign and malignant neoplasms. Notably, and despite their obesity, subjects with the ELS display normoglycemia and hypo-insulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels are responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events.

Congenital IGF-1 deficiency protects from cancer: lessons from Laron syndrome.

Many clinical and experimental studies have implicated the growth hormone (GH)-insulin-like growth factor (IGF-1) axis with the progression of cancer. The epidemiological finding that patients with Laron syndrome (LS), the best-characterized disease under the spectrum of congenital IGF-1 deficiencies, do not develop cancer is of major scientific and translational relevance. The evasion of LS patients from cancer emphasizes the central role of the GH-IGF-1 system in cancer biology. To identify genes that are differentially expressed in LS and that might provide a biological foundation for cancer protection, we have recently conducted genome-wide profiling of LS patients and normal controls. Analyses were performed on immortalized lymphoblastoid cell lines derived from individual patients. Bioinformatic analyses identified a series of genes that are either over- or under-represented in LS. Differential expression was demonstrated in a number of gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT and PI3K-AKT signaling, etc. Major differences between LS and controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. The identification of novel downstream targets of the GH-IGF-1 network highlights the biological complexity of this hormonal system and sheds light on previously unrecognized mechanistic aspects associated with GH-IGF-1 action in the cancer cell.

Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine - comprehensive effects of phytochemicals in primary, secondary and tertiary care.

According to the GLOBOCAN 2020, prostate cancer (PCa) is the most often diagnosed male cancer in 112 countries and the leading cancer-related death in 48 countries. Moreover, PCa incidence permanently increases in adolescents and young adults. Also, the rates of metastasising PCa continuously grow up in young populations. Corresponding socio-economic burden is enormous: PCa treatment costs increase more rapidly than for any other cancer. In order to reverse current trends in exploding PCa cases and treatment costs, pragmatic decisions should be made, in favour of advanced populational screening programmes and effective anti-PCa protection at the level of the health-to-disease transition (sub-optimal health conditions) demonstrating the highest cost-efficacy of treatments. For doing this, the paradigm change from reactive treatments of the clinically manifested PCa to the predictive approach and personalised prevention is essential. Phytochemicals are associated with potent anti-cancer activity targeting each stage of carcinogenesis including cell apoptosis and proliferation, cancer invasiveness and metastatic disease. For example, their positive effects are demonstrated for stabilising and restoring mitochondrial health quality, which if compromised is strongly associated with sub-optimal health conditions and strong predisposition to aggressive PCa sub-types. Further, phytochemicals significantly enhance response of cancer cells to anti-cancer therapies including radio- and chemotherapy. Evident plant-based mitigation of negative side-effects frequently observed for conventional anti-cancer therapies has been reported. Finally, dual anti-cancer and anti-viral effects of phytochemicals such as these of silibinin have been demonstrated as being highly relevant for improved PCa management at the level of secondary and tertiary care, for example, under pandemic conditions, since PCa-affected individuals per evidence are highly vulnerable towards COVID-19 infection. Here, we present a comprehensive data analysis towards clinically relevant anti-cancer effects of phytochemicals to be considered for personalised anti-PCa protection in primary care as well as for an advanced disease management at the level of secondary and tertiary care in the framework of predictive, preventive and personalised medicine.

Marjolin's Ulcer in Laron Syndrome - an Unexpected Combination: A Case Report.

Marjolin's ulcer is an atypical malignancy that develops from deep scars of chronically traumatised skin. Laron syndrome (LS) is a rare autosomal recessive growth retardation from a mutation in the growth hormone receptor (GHR) gene leading to defective GHR, growth hormone insensitivity and eventual low levels of insulin-like growth factor type 1 (IGF-1). Affected individuals present with proportionate dwarfism and other characteristic physical defects, but at the same time are conferred protection against cancer due to low serum levels of IGF-1. We report an exceptional case of Marjolin's ulcer in the foot of a female LS patient 30 years after she sustained flame burns as a 6-month-old baby. Three months before coming to us, she had a 2x3cm ulcer that turned into a rapidly enlarging fungating mass involving the leg, ankle, and foot. Histopathologic analysis of an incision biopsy showed well-differentiated squamous cell carcinoma. The extent of her lesion precluded wide excision. Below knee amputation was done. A second biopsy confirmed the histopathologic diagnosis. This is the first reported case in the literature of Marjolin's ulcer in LS which raises the possibility that IGF-1 deficiency does not completely protect against squamous cell cancer.

Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation.

Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by 'mining' genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines.

Identification of nephronectin as a new target for IGF1 action.

INTRODUCTION: The growth hormone (GH)-insulin-like growth factor-1 (IGF1) endocrine axis has a key role in normal growth and development. Laron syndrome (LS) is a type of dwarfism that results from mutation of the GH receptor, leading to congenital IGF1 deficiency. Epidemiological studies have shown that LS patients are protected from cancer. Genome-wide profiling led to the identification of a series of metabolic genes whose differential expression in LS might be linked to cancer protection. Nephronectin (NPNT) is an intracellular and secreted extracellular matrix protein with important roles in kidney development. NPNT was identified as the top-downregulated gene in LS-derived cells in comparison with ethnic-, age- and gender-matched controls (p-value = 0.0148; fold-change = -3.12 versus controls). NPNT has not been previously linked to the IGF1 signaling pathway. The present study was aimed at evaluating the hypothesis that NPNT is a new target for IGF1 action and that decreased expression of NPNT in LS is correlated with cancer protection. METHODS: Basal and IGF1-stimulated NPNT expression were assessed in LS lymphoblastoid cells as well as in human breast and prostate cancer cells. NPNT silencing experiments were conducted using siRNA methodology. RESULTS: We provide evidence that IGF1 stimulates NPNT expression in LS-derived lymphoblastoids and various cancer cell lines. In addition, we demonstrate that NPNT silencing results in diminished activation of the AKT and ERK1/2 pathways, with ensuing decreases in cellular proliferation. CONCLUSIONS: Our data identified the NPNT gene as a target for IGF1 action. The clinical implications of the functional and physical interactions between NPNT and the IGF1 pathway merit further investigation.

Role of the GH-IGF1 system in progression of cancer.

Emerging evidence links the growth hormone (GH)-insulin-like growth factor-1 (IGF1) endocrine axis to cancer development. While this putative correlation is of major translational relevance, most clinical and epidemiological reports to date found no causal linkage between GH therapy and enhanced cancer risk. Thus, it is generally agreed that GH therapy constitutes a safe pharmacological intervention. The present review focuses on a number of issues in the area of GH-IGF1 action in cancer development. Emphasis is given to the idea that GH and IGF1 do not conform to the definition of oncogenic factors. Specifically, these hormones, even at high pharmacological doses, are unable to induce malignant transformation. However, the GH-IGF1 axis is capable of 'pushing' already transformed cells through the various phases of the cell cycle. Viral and cellular oncogenes require an intact IGF1 signaling pathway in order to elicit transformation; in other words, oncogenic agents adopt the IGF1 pathway. This universal mechanism of action of oncogenes has broad implications in oncology. Our review provides an in-depth analysis of the interplay between the GH-IGF1 axis and cancer genes, including tumor suppressors p53 and BRCA1. Finally, the safety of GH therapy in both children and adults needs further long-term follow-up studies.

Citral prevents UVB-induced skin carcinogenesis in hairless mice.

The incidence of skin cancers has increased worldwide, requiring more prevention of this type of cancer. The use of sunscreen and the control of the time of exposure to sunlight are the recognized forms of prevention. However, new substances have been researched in order to develop formulations with more efficient protective activity. Citral is a natural compound with lemon scent that is used in food and cosmetic industries. The present work evaluated the chemoprotective effect of citral during UVB-induced skin carcinogenesis. Male hairless mice HRS/J, 8-12 weeks old, were exposed to UVB irradiation for 24 weeks, with a cumulative radiation dose of 13.875 J/cm2. Citral (0.1, 0.5 and 1%) was applied to the skin at a dosage of 0.1 g/animal, 5 min after UVB exposure. At the end of the experiment, the number of lesion/animal, and size of lesions were measured. The histological sections of the skin were evaluated for the presence and intensity of actinic keratosis and squamous cell carcinoma. TUNEL assay was performed for apoptosis evaluation. Skin samples were used for the measurement of oxidative stress parameters (total radical-trapping antioxidant parameter of skin, glutathione, catalase activity and malondialdehyde), and cytokines levels (IL-1ß, IL-4, IL-10, IL-23, TNF-α, and IFNγ). Citral 1% completely inhibited UVB-induced skin carcinogenesis by reducing levels of oxidative stress and pro-inflammatory cytokines, increasing apoptotic rate in the skin.

Genome-Wide Profiling of Laron Syndrome Patients Identifies Novel Cancer Protection Pathways.

Laron syndrome (LS), or primary growth hormone resistance, is a prototypical congenital insulin-like growth factor 1 (IGF1) deficiency. The recent epidemiological finding that LS patients do not develop cancer is of major scientific and clinical relevance. Epidemiological data suggest that congenital IGF1 deficiency confers protection against the development of malignancies. This 'experiment of nature' reflects the critical role of IGF1 in tumor biology. The present review article provides an overview of recently conducted genome-wide profiling analyses aimed at identifying mechanisms and signaling pathways that are directly responsible for the link between life-time low IGF1 levels and protection from tumor development. The review underscores the concept that 'data mining' an orphan disease might translate into new developments in oncology.

USA dental health providers' role in HPV vaccine communication and HPV-OPC protection: a systematic review.

Background. Improving human papilloma virus (HPV) vaccination coverage in the US will require healthcare providers to recommend the vaccine more effectively. To inform quality improvement efforts, we systematically reviewed studies of dental provider communication about HPV vaccination. Methods. We searched MEDLINE, CINAHL, ScienceDirect, PsycINFO and JSTOR in August 2018 to identify studies of dental provider knowledge, perceived role and communication about HPV, HPV vaccination and HPV-associated oropharyngeal cancer (HPV-OPC). Results. We identified 10 qualitative and quantitative studies. Results of the primarily descriptive studies showed that although there were some deficiencies in knowledge about HPV-related outcomes and its effect on the male population, most providers understand HPV as a sexually transmitted infection and know the HPV vaccine is available, yet many are not discussing the HPV-OPC link or recommending vaccination. Providers were less often to recommend HPV vaccination if they were uncomfortable discussing sex, perceived parents as hesitant, or believed patients to be low risk. Studies reported mixed results on providers' perceived role in expanded HPV vaccination and HPV-OPC education, but indicated support for the role of professional organizations in promoting awareness. Conclusion. Interventions are needed to help dental providers perceive their role to deliver effective recommendations within the complex communication environment surrounding HPV vaccination and HPV-OPC education.

The Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression.

Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a Cdkn1aSUPER mouse, which harbors an additional Cdkn1a allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous Kras-driven lung adenocarcinoma model, we show that Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1aSUPER allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.

The Pattern of Malignancies in Down Syndrome and Its Potential Context With the Immune System.

The immune surveillance theory of cancer posits that the body's immune system detects and destroys randomly occurring malignant cells. This theory is based on the observation of the increased frequency of malignancies in primary and secondary immunodeficiencies, and is supported by the successful demonstration of immune augmentation in current oncological immune therapy approaches. We review this model in the context of Down syndrome (DS), a condition with a unique tumor profile and various immune defects. Children and adults with DS are more prone to infections due to anatomical reasons and a varying degree of T- and B-cell maturation defects, NK cell dysfunction, and chemotactic or phagocytic abnormalities. However, despite an increased incidence of lymphoblastic and myeloblastic leukemia of infants and children with DS, individuals with DS have a globally decreased incidence of solid tumors as compared to age-adjusted non-DS controls. Additionally, cancers that have been considered "proof of immune therapy principles," such as renal carcinoma, small cell lung carcinoma, and malignant melanoma, are less frequent in adults with DS compared to the general population. Thus, despite the combination of an increased risk of leukemia with detectable immune biological abnormalities and a clinical immunodeficiency, people with DS appear to be protected against many cancers. This observation does not support the immune surveillance theory in the context of DS and indicates a potential tumor-suppressive role for trisomy 21 in non-hematological malignancies.

Differential expression of IGFBPs in Laron syndrome-derived lymphoblastoid cell lines: Potential correlation with reduced cancer incidence.

Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is a growth disorder that results from mutation of the GH-receptor (GHR) gene leading to congenital insulin-like growth factor-1 (IGF-1) deficiency. Recent epidemiological studies have shown that LS patients are protected from cancer development. Genome-wide profiling identified genes and signaling pathways that are differentially represented in LS patients, and that may contribute to cancer protection. The present study was aimed at evaluating the hypothesis that IGF binding proteins (IGFBPs) are differentially expressed in LS, most probably as a result of low circulating levels of IGF-1. Furthermore, we postulated that IGFBPs might be differentially regulated by oxidative stress in this condition and, therefore, may contribute to cancer evasion. Our results show that IGFBP-3, which is predominantly protective, was highly expressed in LS-derived lymphoblastoid cells in comparison to control cells from the same ethnic group. On the other hand, levels of IGFBP-2, -4, -5, and -6 were diminished in LS patients, as demonstrated by RQ-PCR, Western immunoblots and confocal immunofluorescence. In addition, our data provide evidence for a pattern of IGFBP response to H2O2 treatment that might be associated with distinct expression of apoptosis markers (BCL2, pro-caspase-9, pro-caspase-3) in LS. In summary, differential expression of specific IGFBPs in LS might be correlated with cellular mechanisms underlying cancer protection and, probably, additional phenotypes due to congenital IGF-1 deficiency.

Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the APCMIN Mouse Model.

BACKGROUND: Anthocyanin-rich foods and preparations have been reported to reduce the risk of life-style related diseases, including cancer. The SL222 sweet potato, a purple-fleshed cultivar developed in New Zealand, accumulates high levels of anthocyanins in its storage root. METHODS: We examined the chemopreventative properties of the SL222 sweet potato in the C57BL/6J-APC MIN/+ (APCMIN) mouse, a genetic model of colorectal cancer. APCMIN and C57BL/6J wild-type mice (n=160) were divided into four feeding groups consuming diets containing 10% SL222 sweet potato flesh, 10% SL222 sweet potato skin, or 0.12% ARE (Anthocyanin rich-extract prepared from SL222 sweet potato at a concentration equivalent to the flesh-supplemented diet) or a control diet (AIN-76A) for 18 weeks. At 120 days of age, the mice were anaesthetised, and blood samples were collected before the mice were sacrificed. The intestines were used for adenoma enumeration. RESULTS: The SL222 sweet potato-supplemented diets reduced the adenoma number in the APCMIN mice. CONCLUSIONS: These data have significant implications for the use of this sweet potato variant in protection against colorectal cancer.