|CANCER EPIDEMIOLOGY: ORIGINAL ARTICLE
|Year : 2016 | Volume
| Issue : 4 | Page : 189-191
Modified metabolic syndrome and second cancers in women: A case control study
Carlos-Manuel Ortiz-Mendoza1, Ernesto Pérez-Chávez2, Tania-Angélica De-la Fuente-Vera2
1 Department of Surgery, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
2 Department of General Surgery, Hospital General Tacuba, ISSSTE, Mexico City, Mexico
|Date of Web Publication||8-Dec-2016|
Department of Surgery, School of Medicine, National Autonomous University of Mexico, Mexico City
Source of Support: None, Conflict of Interest: None
Background: According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. Aim: To find out the implication of the modified metabolic syndrome in women with second cancers. Materials and Methods: This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases) and age-matched women with only one neoplasm (controls). The analysis comprised: Tumor (s), anthropometric features, and body mass index (BMI); moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. Results: The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 ) was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1). Conclusion: Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.
Keywords: Adult; cancer, female, metabolic syndrome, Mexico, neoplasms, neoplasms, second primary/etiology, obesity
|How to cite this article:|
Ortiz-Mendoza CM, Pérez-Chávez E, Fuente-Vera TAD. Modified metabolic syndrome and second cancers in women: A case control study. South Asian J Cancer 2016;5:189-91
|How to cite this URL:|
Ortiz-Mendoza CM, Pérez-Chávez E, Fuente-Vera TAD. Modified metabolic syndrome and second cancers in women: A case control study. South Asian J Cancer [serial online] 2016 [cited 2019 Sep 15];5:189-91. Available from: http://journal.sajc.org/text.asp?2016/5/4/189/195341
| Introduction|| |
Worldwide the number of cancer survivors is raising; , for example, in the U.S. cancer survivors increased from 3 million in 1971 to over 12 million in 2011.  These survivors are at risk to develop life-threatening second malignancies. ,, Among the multiple sources behind the appearance of these new cancers are obesity, hypertension, and diabetes mellitus. ,,,,, Furthermore, those three diseases makeup elements of a pathologic condition common in cancer survivors: The metabolic syndrome. 
Metabolic syndrome is a cluster of disorders characterized by insulin resistance, hypertension, dyslipidemia, functional endothelial dysfunction, and obesity.  Some researchers have indicated that the metabolic syndrome causes certain malignancies.  Therefore, if this syndrome promotes several primary cancers, there are huge possibilities that in cancer survivors, it may cause second malignancies. However, to our knowledge, there are not studies approaching this issue.
The aim of this case-control study was to find out the plausible implication of the metabolic syndrome in women with second cancers.
| Materials and Methods|| |
Female cancer survivors (survival ≥2 years after completing oncologic treatment) with two or more different cancers were chosen as cases. And for each case three, randomly selected, age-matched female survivors with a neoplasm similar to the first neoplasm of cases, but without a second malignancy, were chosen.
Data collection and definitions
From medical files, recent data concerning: Age, blood pressure, weight and height, as well as, their malignant tumor(s), oncologic treatments, associated diseases (diabetes mellitus, hypertension, and dyslipidemia); medications used and fasting serum levels of glucose, triglycerides, and total cholesterol were obtained.
Recent data were registered from the last semester of clinical follow-up. Blood pressure was measured with a sphygmomanometer in the supine position after a 10-min rest. Weight was determined barefooted and in underwear on a mechanic scale, and recorded to the nearest 0.1 kg, and height was measured with a stadiometer to the closest 0.5 cm. Body mass index (BMI) was calculated: Weight in kilograms divided by the square of height in meters (kg/m 2 ).
Second malignancies were diagnosed when a woman developed distinct cancers (histologically different), in different organs, more than 6 months after diagnosis of the first neoplasia. Diabetes mellitus was diagnosed if the subject used insulin or oral hypoglycemic agents or by fasting serum glucose ≥ 126 mg/dL. Hypertension was diagnosed by use of antihypertensive or blood pressure values ≥ 135/85 mm Hg. Dyslipidemia was diagnosed by use of fibrates, statins or total cholesterol > 199 mg/dL or triglycerides > 149 mg/dL. The modified metabolic syndrome was diagnosed when three of the following parameters appeared simultaneously: Obesity (BMI ≥ 30 kg/m 2 ), previous diagnosis of diabetes mellitus or fasting serum glucose levels > 99 mg/dL, previous diagnosis of hypertriglyceridemia or triglycerides > 149 mg/dL, or previous diagnosis of hypertension or blood pressure ≥ 135/85 mm Hg.
The sample size was calculated using the formula: n = [EDFF × Np (1 − p)]/[(d2/Z21− α/2× (N − 1) + P × (1 − p)], with a 0.05 alpha and a 0.8 beta, with 6% of controls and 54% of cases exposed. All values were expressed either in absolute numbers or percentages. Data were analyzed with the Pearson's "χ2" or exact Fischer's test; the latter when any value was ≤5 in any cell of the 2 × 2 table. Association strength between variables was studied with odds ratio, with a 95% confidence interval. For all analyses, the statistic program OpenEpi version 2 (www.openepi.com) was used, all value of P < 0.05 were considered statistically significant.
| Results|| |
The calculated sample was of 7 cases and 19 controls; however, we increased it to 9 cases and 27 controls. In the cases, the most frequent primary or secondary tumor was breast cancer (11/19, 58%), [Table 1].
Cases were on average heavier than controls; nevertheless, both groups had similar mean high-levels of glucose, cholesterol, and triglycerides [Table 2].
Finally, the data analysis revealed that the modified metabolic syndrome was the most significant risk factor [Table 3].
| Discussion|| |
In this case-control study, at a second-level general hospital, the modified metabolic syndrome was the most significant risk factor in Mexican women with second cancers. This is relevant because world-wide the metabolic syndrome is extremely frequent due to obesity's pandemia.  Particularly, Mexico is facing the greatest incidence of obesity  and so, diseases associated to it have increased, including cancer and the metabolic syndrome.  However, there are no studies regarding the influence of the metabolic syndrome on women's second cancers.
There is, however, ample evidence supporting that the metabolic syndrome is a risk factor for many primary malignancies. It increases the risk for: Breast, ,,,,, endometrial, ,, cervical,  and colorectal cancers. 
Moreover, there are studies documenting that even some of metabolic syndrome's single components increase the risk for some second cancers. Such is the case for obesity (in breast, renal and colorectal cancers), ,, insulin resistance (in breast, renal and colorectal cancers), ,,, hypertension (in breast and renal cancers), , and hypertriglyceridemia (in renal and cervical cancers). , There is also evidence that when these components are associated, but without integrating the syndrome, they considerably increase the risk for some second cancers. ,,
The different impact of individual components and of the full syndrome has also been observed in nononcological areas. Glance et al., for example, showed that individuals with the modified metabolic syndrome are at a significant greater risk of surgical complications than obese subjects without the syndrome. 
The predominance of second breast cancers we found [Table 1] is consistent with different reports of Africa,  America, , Asia,  and Europe.  This is particularly relevant, considering that world-wide breast cancer is one of the main tumors. For example, breast cancer survivors are the most numerous in the U.S. 
The mechanisms involved in the induction of cancer by metabolic syndrome may be multiple, acts synergistically, and are yet poorly understood. The most studied are: Hyperinsulinemia, secondary to insulin resistance, high-levels of glucose and insulin-like growth factor, reduced levels of sex hormone binding-globulin with high free estrogen levels, and high-levels of leptin and fatty acids. ,,,,,,
Often, second malignancies are lethal in cancer survivors because they are detected in advanced stages; ,, perhaps, due to low use of screening studies.  If other researchers corroborate our findings, probably, there is a major need to establish cancer screening studies in survivors with modified metabolic syndrome. In addition, future studies should address whether or not metabolic syndrome's treatment may decrease the incidence of second malignancies in cancer survivors; particularly, that of its key etiological component: The obesity.
We are quite aware of the limitations of this study, which include a rather small sample size a population of a single hospital, a heterogeneous group of cancers, and the lack of waist circumference data. Our findings are, nonetheless, in line with those reported by most other studies of the relationship between the metabolic syndrome and cancer.
| Conclusion|| |
We suggest that the modified metabolic syndrome in women survivors of cancer may be a risk factor for second neoplasms. If others corroborate our findings, there is a greater need to launch screening studies in cancer survivors with the metabolic syndrome.
| Acknowledgments|| |
We thank to Dr. Dieter Mascher Gramlich, for his invaluable opinions about the final draft of the manuscript and contributed immensely to its improvement.
| References|| |
Edgington A, Morgan MA. Looking beyond recurrence: Comorbidities in cancer survivors. Clin J Oncol Nurs 2011;15:E3-12.
Valdivieso M, Kujawa AM, Jones T, Baker LH. Cancer survivors in the United States: A review of the literature and a call to action. Int J Med Sci 2012;9:163-73.
Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple primary malignancies- Epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.
VanderWalde AM, Hurria A. Second malignancies among elderly survivors of cancer. Oncologist 2011;16:1572-81.
Youlden DR, Baade PD. The relative risk of second primary cancers in Queensland, Australia: A retrospective cohort study. BMC Cancer 2011;11:83.
Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, et al
. Cancer incidence and mortality in relation to body mass index in the Million Women Study: Cohort study. BMJ 2007;335:1134.
Li CI, Daling JR, Porter PL, Tang MT, Malone KE. Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. J Clin Oncol 2009;27:5312-8.
Pi-Sunyer X. The medical risks of obesity. Postgrad Med 2009;121:21-33.
Maskarinec G, Pagano I, Lurie G, Bantum E, Gotay CC, Issell BF. Factors affecting survival among women with breast cancer in Hawaii. J Womens Health (Larchmt) 2011;20:231-7.
Brooks JD, John EM, Mellemkjær L, Reiner AS, Malone KE, Lynch CF, et al.
Body mass index and risk of second primary breast cancer: The WECARE Study. Breast Cancer Res Treat 2012;131:571-80.
De Haas EC, Oosting SF, Lefrandt JD, Wolffenbuttel BH, Sleijfer DT, Gietema JA. The metabolic Syndrome in cancer survivors. Lancet Oncol 2010;11:193-203.
Russo A, Autelitano M, Bisanti L. Metabolic syndrome and cancer risk. Eur J Cancer 2008;44:293-7.
Elder JP. Mexico and the USA: The world's leaders in the obesity epidemic. Salud Publica Mex 2013;55 Suppl 3:355.
Cárdenas-Sánchez J, Erazo-Valle A, Maafs E, Poitevin A. National consensus on diagnosis and treatment of breast cancer. Fourth revision. Colima, Mexico. GAMO 2011;10:1-58.
Agnoli C, Berrino F, Abagnato CA, Muti P, Panico S, Crosignani P, et al.
Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: A nested case-control study. Nutr Metab Cardiovasc Dis 2010;20:41-8.
Bjørge T, Lukanova A, Jonsson H, Tretli S, Ulmer H, Manjer J, et al.
Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project. Cancer Epidemiol Biomarkers Prev 2010;19:1737-45.
Capasso I, Esposito E, Pentimalli F, Crispo A, Montella M, Grimaldi M, et al.
Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience. Cancer Biol Ther 2010;10:1240-3.
Healy LA, Ryan AM, Carroll P, Ennis D, Crowley V, Boyle T, et al.
Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer. Clin Oncol (R Coll Radiol) 2010;22:281-8.
Porto LA, Lora KJ, Soares JC, Costa LO. Metabolic syndrome is an independent risk factor for breast cancer. Arch Gynecol Obstet 2011;284:1271-6.
Osaki Y, Taniguchi S, Tahara A, Okamoto M, Kishimoto T. Metabolic syndrome and incidence of liver and breast cancers in Japan. Cancer Epidemiol 2012;36:141-7.
Bjørge T, Stocks T, Lukanova A, Tretli S, Selmer R, Manjer J, et al
. Metabolic syndrome and endometrial carcinoma. Am J Epidemiol 2010;171:892-902.
Rosato V, Zucchetto A, Bosetti C, Dal Maso L, Montella M, Pelucchi C, et al.
Metabolic syndrome and endometrial cancer risk. Ann Oncol 2011;22:884-9.
Friedenreich CM, Biel RK, Lau DC, Csizmadi I, Courneya KS, Magliocco AM, et al.
Case-control study of the metabolic syndrome and metabolic risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev 2011;20:2384-95.
Stocks T, Rapp K, Bjørge T, Manjer J, Ulmer H, Selmer R, et al.
Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): Analysis of six prospective cohorts. PLoS Med 2009;6:E1000201.
Häggström C, Rapp K, Stocks T, Manjer J, Bjørge T, Ulmer H, et al.
Metabolic factors associated with risk of renal cell carcinoma. PLoS One 2013;8:E57475.
Oh SW, Park CY, Lee ES, Yoon YS, Lee ES, Park SS, et al.
Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: A cohort study. Breast Cancer Res 2011;13:R34.
Pais R, Silaghi H, Silaghi AC, Rusu ML, Dumitrascu DL. Metabolic syndrome and risk of subsequent colorectal cancer. World J Gastroenterol 2009;15:5141-8.
Goodwin PJ, Ennis M, Bahl M, Fantus IG, Pritchard KI, Trudeau ME, et al.
High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome. Breast Cancer Res Treat 2009;114:517-25.
Sánchez L, Lana A, Hidalgo A, Rodríguez JM, Del Valle M del O, Cueto A, et al
. Risk factors for second primary tumours in breast cancer survivors. Eur J Cancer Prev 2008;17:406-13.
Borena W, Stocks T, Jonsson H, Strohmaier S, Nagel G, Bjørge T, et al.
Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study. Cancer Causes Control 2011;22:291-9.
Ortiz-Mendoza CM, Velasco-Navarro C. Obesity, a main risk factor for endometrial cancer. Rev Med Inst Mex Seguro Soc 2013;51:260-3.
Glance LG, Wissler R, Mukamel DB, Li Y, Diachun CA, Salloum R, et al.
Perioperative outcomes among patients with the modified metabolic syndrome who are undergoing noncardiac surgery. Anesthesiology 2010;113:859-72.
Mehdi I, Shah AH, Moona MS, Verma K, Abussa A, Elramih R, et al.
Synchronous and metachronous malignant tumours expect the unexpected. J Pak Med Assoc 2010;60:905-9.
Vidal-Millan S, Zeichner-Gancz I, Flores-Estrada D, Vela-Rodríguez BE, Vazquez-López MI, Robles-Vidal CD, et al
. A descriptive study of second primary malignancies associated to breast cancer in a mexican Hispanic population. Med Oncol 2005;22:17-22.
Lee KD, Chen SC, Chan CH, Lu CH, Chen CC, Lin JT, et al.
Increased risk for second primary malignancies in women with breast cancer diagnosed at young age: A population-based study in Taiwan. Cancer Epidemiol Biomarkers Prev 2008;17:2647-55.
Lana Pérez A, Folgueras Sánchez MV, Díaz Rodríguez S, del Olivo del Valle Gómez M, Cueto Espinar A, López González ML. Survival analysis in multiple cancer patients in Asturias, Spain, 1975-2004. Rev Esp Salud Publica 2008;82:167-77.
Grunfeld E, Moineddin R, Gunraj N, Del Giudice ME, Hodgson DC, Kwon JS, et al.
Cancer screening practices of cancer survivors: Population-based, longitudinal study. Can Fam Physician 2012;58:980-6.
[Table 1], [Table 2], [Table 3]