Effect of a Low-Fat Diet on the Incidence of Actinic Keratosis

Black, Homer S.; Herd, J. Alan; Goldberg, Leonard Harry; Wolf, John E.; Thornby, John; Rosen, Theodore; Bruce, Suzanne; Tschen, Jaime A.; Foreyt, John P.; Scott, Lynne W.; Jaax, Suzanne; Andrews, Kelly

doi:10.1056/nejm199405053301804

Cited by 150 publications

(85 citation statements)

References 15 publications

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“…Subsequently, Black and his colleagues confirmed the stimulatory effect of a high fat diet on UV-induced formation of skin tumors in mice, and they provided evidence for an association of high-fat diets with actinic keratosis and skin cancer in humans (14)(15)(16)(17). Recently, prospective studies indicated that high-fat diets increased the risk of squamous cell carcinomas, and individuals with a high body mass index were at a higher risk of contracting skin cancer than individuals with a low body mass index (18,19).…”

Section: Discussionmentioning

confidence: 99%

Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet

Lü

Lou

Bernard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Removal of the parametrial fat pads (partial lipectomy) from female SKH-1 mice fed a high-fat diet inhibited UVB-induced carcinogenesis, but this was not observed in mice fed a low-fat chow diet. Partial lipectomy in high-fat-fed mice decreased the number of keratoacanthomas and squamous cell carcinomas per mouse by 76 and 79%, respectively, compared with sham-operated control mice irradiated with UVB for 33 wk. Immunohistochemical analysis indicated that partial lipectomy increased caspase 3 (active form) positive cells by 48% in precancerous epidermis away from tumors, by 68% in keratoacanthomas, and by 224% in squamous cell carcinomas compared with sham-operated control mice. In addition, partial lipectomy decreased cell proliferation away from tumors and in tumors. RT-PCR analysis for adipokines revealed that mRNAs for TIMP1, MCP1, and SerpinE1 (proinflammatory/antiapoptotic cytokines) in the parametrial fat pads of sham-operated control mice were 54-to 83-fold higher than levels in compensatory fat that returned after surgery in partially lipectomized mice at the end of the tumor study. Feeding mice high-fat diets for 2 wk increased levels of TIMP1 and other adipokines in serum and epidermis, and these increases were inhibited by removal of the parametrial fat pads. Our results are a unique demonstration that surgical removal of a specific tissue fat results in inhibition of carcinogenesis in obese mice. This inhibition was associated with an increase in apoptosis and a decrease in proliferation in tumors and in precancerous areas away from tumors.obesity | skin cancer S unlight-induced nonmelanoma skin cancer is a major cancer in the United States (1-4), and rates of obesity are also dramatically increasing, leading to an alarming rise in morbidity and mortality caused by heart disease, diabetes, and cancer. How obesity contributes to skin cancer and the molecular changes induced by obesity that promote skin cancer development remain poorly understood. Therefore, approaches for preventing these cancers are of considerable importance. Early studies in our laboratory indicated that orally administered caffeine to UVB-pretreated "high-risk" SKH-1 mice decreased tissue fat as measured by the size of the parametrial fat pads and the thickness of the dermal fat layer (5), and this treatment also decreased tumor formation (6). Mechanistic studies suggested that the stimulatory effect of caffeine administration on locomotor activity contributed to the effect of caffeine on tissue fat (7). Our results also showed that voluntary running wheel exercise decreased the weight of the parametrial fat pads, which was associated with decreased UVB-induced formation of skin tumors as well as the size of the tumors (8). Additional observations indicated that a combination of caffeine administration and running wheel exercise was more effective than either treatment alone at decreasing tissue fat and enhancing UVB-induced apoptosis (9). In a recent study, we found that running wheel exercise together with oral administration o...

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Section: Discussionmentioning

confidence: 99%

Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet

Lü

Lou

Bernard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…In a randomized clinical trial, one hundred patients who had already developed one non-melanoma skin cancer were placed on either a normal or a low-fat diet, and followed for 2 years for the development of skin cancer (Black et al, 1995). A low-fat diet was found to reduce significantly the occurrence of BCCs in this randomized, cohort study (Black et al, 1994;Black et al, 1995). However, subsequent observational studies using questionnaires to assess diet failed to find a protective effect of a low fat diet against BCC carcinogenesis (McNaughton et al, 2005).…”

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confidence: 90%

Novel Hedgehog pathway targets against basal cell carcinoma

Tang

Epstein

2007

Toxicology and Applied Pharmacology

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The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastro-intestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence. Epidemiology of Basal cell carcinoma (BCC)Basal cell carcinoma (BCC), the most common of all human cancers, affects close to 1 million Americans a year. Over the past 40 years there has been a dramatic increase in the incidence of BCC, and it is estimated that nearly 30% of Caucasians living in areas of high ambient sun exposure will develop a BCC (Miller and Weinstock, 1994). Furthermore, the incidence of BCC is rising in younger populations, especially among women (Christenson et al., 2005). Although the case fatality rate of BCCs is low, the high incidence and frequent occurrence of multiple primary tumors in affected individuals leads to significant morbidity. BCCs characteristically arise in sun-exposed body areas, most commonly on the head and neck, but also occur on the trunk and extremities. There are three accepted environmental insults for BCC development: ultraviolet radiation (UV), ionizing radiation (IR), and arsenic. Interindividual differences in the susceptibility to BCC development have been recognized for many years. Epidemiologic studies have identified phenotypic features such as fair skin and freckling tendency that are associated with an increased susceptibility to BCCs (Rubin et al., 2005).It is generally accepted that BCC can be caused by UV exposure from the sun. While the risk of squamous cell carcinoma is strongly related to cumulative sun exposure, sunlight's exact role in BCC development remains less clear (Armstrong and Kricker, 2001). Thus, epidemiologic studies have shown that BCC risk correlates better with intermittent sun exposure (i.e. childhood sunburns, weekend sun exposure) than with cumulative lifetime sun exposure (Corona et al., 2001). Hence, the timing, dose, and duration of UV exposure are critical to carcinogenesis, but UV seems to have a different role in SCC versus BCC carcinogenesis development. Consistent with this, a randomized clinical trial of daily sunscreen use showed that sunscreen reduced the incidence of SCC but not BCC. The daily application of an SPF 15 sunscreen to the head, neck, arms, and hands over a 4-5 year period had no e...

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“…These variables include the ingestion of fat with different compositions in different individuals, differences in caloric intake among different individuals, and differences in gene͞environment͞lifestyle interactions among different individuals. A carefully controlled randomized intervention trial in human subjects indicated that reducing the percentage of fat calories from 39% to 21% of total calories caused a marked reduction in the number of actinic keratoses (precancerous lesions) and nonmelanoma skin cancers (47)(48)(49). Although the latter intervention trial indicates that decreasing the level of dietary fat can inhibit the formation of UV-induced skin tumors in humans (possibly by enhancing apoptosis), even this carefully done study may also be affected by confounding variables such as substances that were added to the diet to replace fat.…”

Section: Table 4 Effects Of Partial Lipectomy (Surgical Removal Of Tmentioning

confidence: 99%

Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice

Lou

Nolan³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Earlier studies indicated that high dietary fat and obesity are associated with an increased risk of cancer at several organ sites in experimental animals and in humans. In a recent study we found that voluntary running wheel exercise decreased body fat and inhibited ultraviolet B light (UVB)-induced carcinogenesis in the epidermis of SKH-1 mice. In the present study we demonstrate that voluntary running wheel exercise stimulated UVB-induced apoptosis in the epidermis by a p53-independent mechanism, and voluntary exercise also stimulated apoptosis in UVB-induced tumors in tumor-bearing mice. Exercise had no effect in non-UVB-treated epidermis or in areas of the epidermis away from tumors in tumor-bearing mice. In addition, we found that removal of the parametrial fat pads (partial lipectomy) 2 weeks before UVB irradiation enhanced UVB-induced apoptosis. The results of our studies suggest that fat cells secrete substances that inhibit apoptosis in cells with DNA damage and possibly also in tumors. Our results help explain why exercise or various dietary regimens that decrease tissue fat inhibit carcinogenesis.carcinogenesis ͉ sunburn ͉ cancer prevention ͉ sun-induced skin cancer

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Effect of a Low-Fat Diet on the Incidence of Actinic Keratosis

Abstract: In patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the incidence of actinic keratosis.

Cited by 150 publications

References 15 publications

Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet

Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet

Novel Hedgehog pathway targets against basal cell carcinoma

Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice

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