- Email: [email protected]
Statins and cancer: Harmful or helpful?
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Letters to the Editor / Maturitas 68 (2011) 197–199
Statins and cancer: Harmful or helpful? HMG-CoA inhibitors also known as statins are one of the most prescribed therapeutic drug class in developed countries after analgesics. Although these drugs are used primarily to decrease cholesterol levels in patients with dyslipidemia, numerous studies have investigated the pleiotropic effects of statins and their potential role in the prevention or origin of other diseases, including cancer. Several theories have been suggested to explain how statins may affect the risk or development of malignancies. Studies have revealed statins to be associated with both increased and decreased cancer risk; however, most of the published studies have been observational and retrospective, and most prospective trials evaluated cancer as a secondary end point or adverse event, making it difficult to assess causality. Few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed have been detected [1]. Data related to effects of statins on cancer prognosis and secondary prevention are scant; with the sole exception of consistent evidence that statins are associated with reduced risk of prostate cancer [2] and that like estrogens, may have a potential role as preventive agents in colon adenocarcinoma [3,4]. Conversely, much has been discussed on the use and effects of statins and breast cancer risk, and opposite to Mascitelli comment [5], evidence suggesting that statins inhibited the proliferation of breast cancer cells both in vitro, in animal models and in preclinical studies with humans have been found and therefore, interest in whether the use of statins might decrease in woman the risk of developing breast cancer have raised [6]. However, Goldstein and Mascitelli have recently published a report suggesting that statins increase cancer risk at the expense of decreasing cardiovascular diseases, therefore, reopening the question between statin use and cancer [7]. On the other hand a meta-analyses by Browing and Martin [8] reported that statins were not associated with a significantly increased or decreased overall risk of several tumors including lung, breast, colorectal, prostate, genitourinary, melanoma, and haematological malignancies. Many studies have demonstrated the possible antitumor effects of statins through pro-apoptotic, growth inhibitory, and prodifferentiation responses of neoplastic cells. Moreover, several cellular pathways, e.g., activation of JNK kinase and inhibition of MEK/Erk pathways, leading to induction of apoptosis and/or cell cycle arrest that are triggered by statins have been identified [9,10]. Likewise, Sanchez et al. have reported that statin-induced inhibition of MCF7 breast cancer cell proliferation, and that this action is related to cell cycle arrest and apoptotic cell death mediated by an enhanced oxidative stress [9]. In summary, statins appear to be safe in relation to cancer risk but any chemopreventive effect or any risk increase effect in human remains to be confirmed; thus, its use with other indications than lowering cholesterol should not be recommended outside the context of clinical trials.
Competing interest No competing interests. References [1] Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 2010;9(4):603–21. Jul. [2] Hamilton RJ, Freedland SJ. Rationale for statins in the chemoprevention of prostate cancer. Curr Urol Rep 2008;9(3):189–96. May. [3] Baron JA. Statins and the colorectum: hope for chemoprevention? Cancer Prev Res (Phila) 2010;3(May (5)):573–5.
[4] Lipkin SM, Chao EC, Moreno V, et al. Genetic variation in 3-hydroxy-3methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. Cancer Prev Res (Phila) 2010;3(May (5)):597–603 [Epub 2010 April 19]. [5] Mascitelli L, Goldstein MR. Menopause, estrogen, statins, and the immune system. Maturitas 2010. [6] Mannello F, Tonti GA. Statins and breast cancer: may matrix metalloproteinase be the missing link. Cancer Invest 2009;27(May (4)):466–70 [Review]. [7] Goldstein MR, Mascitelli L, Pezzetta F. Cholesterol, statins, and mortality. Lancet 2008;371:1161. [8] Browing DR, Martin RM. Statins and risk of cancer: a systematic review and meta-analysis. Int J Cancer 2008;120:833–43. [9] Sanchez CA, Rodriguez E, Varela E, et al. Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest 2008;26:698–707. [10] Sassano A, Platanias LC. Statins in tumor suppression. Cancer Lett 2008;260:11–9.
Camil Castelo-Branco Department Obstetrics & Gynecology, University of Barcelona, Clinic Institute of Gynecology, Obstetrics & Neonatology, Hospital Clínic, Villarroel 170, 08036-Barcelona, Spain E-mail address: [email protected] 5 November 2010 doi:10.1016/j.maturitas.2010.11.004
Chocolate in health & disease: Not so sweet Keywords: Cardiovascular Chocolate Isoflavones
Dear Editor, We read your article with interest [1]. From your wellresearched piece, it is clear that there is lots of evidence to suggest that chocolate is useful in the protection against many diseases. However, there are a number of points that we feel need to be addressed. It may be slightly misleading to quote all of these positives without proper clarification. A recent study by Mostofsky et al. [2] suggests that habitual chocolate intake in middle and old-aged females was associated with a lower risk of heart failure hospitalisation and death, but chocolate intake was not protective when intake was >1 serving per day. Also, critical attention must be paid to the manufacturing process of chocolate, which significantly reduces isoflavone concentration, and one must take into account the high fat and sugar content in chocolate snacks. It is clear that these questions need to be addressed. Perhaps the development of new low-calorie snacks and beverages will be the future. It is also clear that the studies on cocoa at present are few and have small sample sizes. Thus it is important that cocoacontaining products are not recommended until large long-term clinical trials looking at isoflavone intake are performed. Importance must be attributed to the pharmacological viewpoint and the assessment of the long-term side-effect profiles, especially of high-dose regimens [3]. One must also clarify whether there are any age and gender differences when analysing response to cocoa products. Competing interest No competing interest.
Letters to the Editor / Maturitas 68 (2011) 197–199
Statins and cancer: Harmful or helpful? HMG-CoA inhibitors also known as statins are one of the most prescribed therapeutic drug class in developed countries after analgesics. Although these drugs are used primarily to decrease cholesterol levels in patients with dyslipidemia, numerous studies have investigated the pleiotropic effects of statins and their potential role in the prevention or origin of other diseases, including cancer. Several theories have been suggested to explain how statins may affect the risk or development of malignancies. Studies have revealed statins to be associated with both increased and decreased cancer risk; however, most of the published studies have been observational and retrospective, and most prospective trials evaluated cancer as a secondary end point or adverse event, making it difficult to assess causality. Few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed have been detected [1]. Data related to effects of statins on cancer prognosis and secondary prevention are scant; with the sole exception of consistent evidence that statins are associated with reduced risk of prostate cancer [2] and that like estrogens, may have a potential role as preventive agents in colon adenocarcinoma [3,4]. Conversely, much has been discussed on the use and effects of statins and breast cancer risk, and opposite to Mascitelli comment [5], evidence suggesting that statins inhibited the proliferation of breast cancer cells both in vitro, in animal models and in preclinical studies with humans have been found and therefore, interest in whether the use of statins might decrease in woman the risk of developing breast cancer have raised [6]. However, Goldstein and Mascitelli have recently published a report suggesting that statins increase cancer risk at the expense of decreasing cardiovascular diseases, therefore, reopening the question between statin use and cancer [7]. On the other hand a meta-analyses by Browing and Martin [8] reported that statins were not associated with a significantly increased or decreased overall risk of several tumors including lung, breast, colorectal, prostate, genitourinary, melanoma, and haematological malignancies. Many studies have demonstrated the possible antitumor effects of statins through pro-apoptotic, growth inhibitory, and prodifferentiation responses of neoplastic cells. Moreover, several cellular pathways, e.g., activation of JNK kinase and inhibition of MEK/Erk pathways, leading to induction of apoptosis and/or cell cycle arrest that are triggered by statins have been identified [9,10]. Likewise, Sanchez et al. have reported that statin-induced inhibition of MCF7 breast cancer cell proliferation, and that this action is related to cell cycle arrest and apoptotic cell death mediated by an enhanced oxidative stress [9]. In summary, statins appear to be safe in relation to cancer risk but any chemopreventive effect or any risk increase effect in human remains to be confirmed; thus, its use with other indications than lowering cholesterol should not be recommended outside the context of clinical trials.
Competing interest No competing interests. References [1] Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 2010;9(4):603–21. Jul. [2] Hamilton RJ, Freedland SJ. Rationale for statins in the chemoprevention of prostate cancer. Curr Urol Rep 2008;9(3):189–96. May. [3] Baron JA. Statins and the colorectum: hope for chemoprevention? Cancer Prev Res (Phila) 2010;3(May (5)):573–5.
[4] Lipkin SM, Chao EC, Moreno V, et al. Genetic variation in 3-hydroxy-3methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. Cancer Prev Res (Phila) 2010;3(May (5)):597–603 [Epub 2010 April 19]. [5] Mascitelli L, Goldstein MR. Menopause, estrogen, statins, and the immune system. Maturitas 2010. [6] Mannello F, Tonti GA. Statins and breast cancer: may matrix metalloproteinase be the missing link. Cancer Invest 2009;27(May (4)):466–70 [Review]. [7] Goldstein MR, Mascitelli L, Pezzetta F. Cholesterol, statins, and mortality. Lancet 2008;371:1161. [8] Browing DR, Martin RM. Statins and risk of cancer: a systematic review and meta-analysis. Int J Cancer 2008;120:833–43. [9] Sanchez CA, Rodriguez E, Varela E, et al. Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest 2008;26:698–707. [10] Sassano A, Platanias LC. Statins in tumor suppression. Cancer Lett 2008;260:11–9.
Camil Castelo-Branco Department Obstetrics & Gynecology, University of Barcelona, Clinic Institute of Gynecology, Obstetrics & Neonatology, Hospital Clínic, Villarroel 170, 08036-Barcelona, Spain E-mail address: [email protected] 5 November 2010 doi:10.1016/j.maturitas.2010.11.004
Chocolate in health & disease: Not so sweet Keywords: Cardiovascular Chocolate Isoflavones
Dear Editor, We read your article with interest [1]. From your wellresearched piece, it is clear that there is lots of evidence to suggest that chocolate is useful in the protection against many diseases. However, there are a number of points that we feel need to be addressed. It may be slightly misleading to quote all of these positives without proper clarification. A recent study by Mostofsky et al. [2] suggests that habitual chocolate intake in middle and old-aged females was associated with a lower risk of heart failure hospitalisation and death, but chocolate intake was not protective when intake was >1 serving per day. Also, critical attention must be paid to the manufacturing process of chocolate, which significantly reduces isoflavone concentration, and one must take into account the high fat and sugar content in chocolate snacks. It is clear that these questions need to be addressed. Perhaps the development of new low-calorie snacks and beverages will be the future. It is also clear that the studies on cocoa at present are few and have small sample sizes. Thus it is important that cocoacontaining products are not recommended until large long-term clinical trials looking at isoflavone intake are performed. Importance must be attributed to the pharmacological viewpoint and the assessment of the long-term side-effect profiles, especially of high-dose regimens [3]. One must also clarify whether there are any age and gender differences when analysing response to cocoa products. Competing interest No competing interest.