The metabolic changes present in the metabolic syndrome (MetS) have been associated with increased risk of pancreatic and colon cancers; however, there is little information about the association between MetS and cervical cancer risk. We performed a case-control study using data from the National Health and Nutrition Examination Survey (NHANES) between 1999–2010. We identified women 21 years of age and older, of which an estimated 585,924 (2.3% of the sample) self-reported a history of cervical cancer (cases). About half (48.6%) of cases and 33.2% of controls met criteria for MetS. Logistic regression analysis showed increased odds of history of cervical cancer among women with MetS ( ; 95% CI 1.06, 3.42; value ≤ 0.05) for the risk of history of cervical cancer among women with MetS while adjusting for other known risk factors (high number of lifetime sexual partners, multiparty, history of hormonal contraceptive use, and history of smoking) ( ; 95% CI 1.02, 3.26; value ≤ 0.05). In this US surveyed population we found increased odds of history of cervical cancer among subjects with MetS. 1. Introduction Cervical cancer is the second most common cancer in women worldwide, killing approximately 274,000 women in 2008, most of them in developing countries [1]. In the USA, cervical cancer cases are declining [2], but every year there continue to be about 12,000 incident cases and 4,000 deaths from this disease [3]. The causal relationship between infection with the human Papilloma Virus (HPV) and the development of cervical cancer has been established in the last two decades [4]. Out of the approximately 150 identified genotypes of HPV, 12 have been classified as category 1 carcinogens, meaning that there is sufficient evidence to determine that they cause cancer in humans [5]. Some of those types are linked to cancers other than cervical, namely, vulvar, vaginal, perianal, penis, and oropharyngeal [5]. Serotypes 16 and 18 are responsible for about 70% of all the cervical cancer cases [6, 7], but HPV 16 alone causes at least half of all cervical cancers [8]. HPV 16 is also less associated with adenocarcinoma than with squamous cell carcinoma of the cervix, which makes up more than 95% of all cervical cancers [9, 10]. HPV infection is highly prevalent among sexually active young women [6, 11], but the large majority (more than 90%) of HPV infections will clear over a few years [12]. The transition from infection with one of the oncogenic types of HPV to the immediate precursor of cervical cancer (cervical intraepithelial neoplasia 3 (CIN 3)), to invasive
References
[1]
J. Ferlay, H. R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, “Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008,” International Journal of Cancer, vol. 127, no. 12, pp. 2893–2917, 2010.
[2]
P. A. Wingo, C. J. Cardinez, S. H. Landis, L. A. G. Ries, R. N. Anderson, and M. J. Thun, “Long-term trends in cancer mortality in the United States, 1930–1998,” Cancer, vol. 97, no. 12, supplement, pp. 3133–3275, 2003.
[3]
A. Jemal, R. Siegel, J. Xu, and E. Ward, “Cancer statistics, 2010,” CA Cancer Journal for Clinicians, vol. 60, no. 5, pp. 277–300, 2010.
[4]
F. X. Bosch, A. Lorincz, N. Mu？oz, C. J. L. M. Meijer, and K. V. Shah, “The causal relation between human papillomavirus and cervical cancer,” Journal of Clinical Pathology, vol. 55, no. 4, pp. 244–265, 2002.
[5]
V. Bouvard, R. Baan, K. Straif et al., “A review of human carcinogens—part B: biological agents,” The Lancet Oncology, vol. 10, no. 4, pp. 321–322, 2009.
[6]
M. Schiffman, N. Wentzensen, S. Wacholder, W. Kinney, J. C. Gage, and P. E. Castle, “Human papillomavirus testing in the prevention of cervical cancer,” Journal of the National Cancer Institute, vol. 103, no. 5, pp. 368–383, 2011.
[7]
N. Li, S. Franceschi, R. Howell-Jones, P. J. F. Snijders, and G. M. Clifford, “Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication,” International Journal of Cancer, vol. 128, no. 4, pp. 927–935, 2011.
[8]
I. W. G. o .t. E. o. C. R. t. Humans, “Human papillomaviruses,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 90, pp. 1–636, 2007.
[9]
S. de Sanjose, W. G. V. Quint, L. Alemany et al., “Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study,” The Lancet Oncology, vol. 11, no. 11, pp. 1048–1056, 2010.
[10]
H. O. Smith, M. F. Tiffany, C. R. Qualls, and C. R. Key, “The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States—a 24-year population-based study,” Gynecologic Oncology, vol. 78, no. 2, pp. 97–105, 2000.
[11]
K. A. Ault, “Epidemiology and natural history of human papillomavirus infections in the female genital tract,” Infectious Diseases in Obstetrics and Gynecology, vol. 2006, Article ID 40470, 5 pages, 2006.
[12]
J. Cuzick, A. Szarewski, H. Cubie et al., “Management of women who test positive for high-risk types of human papillomavirus: the HART study,” The Lancet, vol. 362, no. 9399, pp. 1871–1876, 2003.
[13]
A. C. Rodriguez, M. Schiffman, R. Herrero et al., “Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection,” Journal of the National Cancer Institute, vol. 102, no. 5, pp. 315–324, 2010.
[14]
M. R. McCredie, K. J. Sharples, C. Paul et al., “Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study,” The Lancet Oncology, vol. 9, no. 5, pp. 425–434, 2008.
[15]
P. Appleby, V. Beral, A. Berrington De González et al., “Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies,” International Journal of Cancer, vol. 118, no. 6, pp. 1481–1495, 2006.
[16]
L. A. Brinton, R. F. Hamman, G. R. Huggins, et al., “Sexual and reproductive risk factors for invasive squamous cell cervical cancer,” Journal of the National Cancer Institute, vol. 79, no. 1, pp. 23–30, 1987.
[17]
J. S. Smith, J. Green, A. Berrington De Gonzalez et al., “Cervical cancer and use of hormonal contraceptives: a systematic review,” The Lancet, vol. 361, no. 9364, pp. 1159–1167, 2003.
[18]
K. G. M. M. Alberti, R. H. Eckel, S. M. Grundy et al., “Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; And international association for the study of obesity,” Circulation, vol. 120, no. 16, pp. 1640–1645, 2009.
[19]
E. Giovannucci, D. M. Harlan, M. C. Archer et al., “Diabetes and cancer: a consensus report,” CA Cancer Journal for Clinicians, vol. 60, no. 4, pp. 207–221, 2010.
[20]
E. Giovannucci and D. Michaud, “The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas,” Gastroenterology, vol. 132, no. 6, pp. 2208–2225, 2007.
[21]
S. Cowey and R. W. Hardy, “The metabolic syndrome: a high-risk state for cancer?” American Journal of Pathology, vol. 169, no. 5, pp. 1505–1522, 2006.
[22]
J. A. Laukkanen, D. E. Laaksonen, L. Niskanen, E. Pukkala, A. Hakkarainen, and J. T. Salonen, “Metabolic syndrome and the risk of prostate cancer in finnish men: a population-based study,” Cancer Epidemiology Biomarkers and Prevention, vol. 13, no. 10, pp. 1646–1650, 2004.
[23]
T. Stocks, A. Lukanova, M. Johansson et al., “Components of the metabolic syndrome and colorectal cancer risk; a prospective study,” International Journal of Obesity, vol. 32, no. 2, pp. 304–314, 2008.
[24]
Centers for Disease Control and Prevention, National Center for Health Statistics, National Health and Nutrition Examination Survey 1999-2000, 2001-2002, 2003-2004, 2005-2006, and 2007-2008 documentation files, vol. 2011.
[25]
“Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—the Evidence Report. National Institutes of Health,” Obesity Research, vol. 6, supplement 2, pp. 51S–209S, 1998.
[26]
J. Green, A. Berrington De Gonzalez, S. Sweetland et al., “Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National Case—Control Study of Cervical Cancer,” British Journal of Cancer, vol. 89, no. 11, pp. 2078–2086, 2003.
[27]
H. Ulmer, T. Bj？rge, H. Concin et al., “Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me-Can),” Gynecologic Oncology, vol. 125, no. 2, pp. 330–335, 2012.
[28]
L. A. Colangelo, S. M. Gapstur, P. H. Gann, A. R. Dyer, and K. Liu, “Colorectal cancer mortality and factors related to the insulin resistance syndrome,” Cancer Epidemiology Biomarkers and Prevention, vol. 11, no. 4, pp. 385–391, 2002.
[29]
M. Trevisan, J. Liu, P. Muti, G. Misciagna, A. Menotti, and F. Fucci, “Markers of insulin resistance and colorectal cancer mortality,” Cancer Epidemiology Biomarkers and Prevention, vol. 10, no. 9, pp. 937–941, 2001.
[30]
H. Tulinius, N. Sigfússon, H. Sigvaldason, K. Bjarnadóttir, and L. Tryggvadóttir, “Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders,” Cancer Epidemiology Biomarkers and Prevention, vol. 6, no. 11, pp. 863–873, 1997.
[31]
G. Ursin, M. C. Pike, S. Preston-Martin, G. D'Ablaing, and R. K. Peters, “Sexual, reproductive, and other risk factors for adenocarcinoma of the cervix: results from a population-based case-control study (California, United States),” Cancer Causes and Control, vol. 7, no. 3, pp. 391–401, 1996.
[32]
S. H. Jee,, H. Ohrr, W. S. Jae, E. Y. Ji, M. Ji, and J. M. Samet, “Fasting serum glucose level and cancer risk in Korean men and women,” Journal of the American Medical Association, vol. 293, no. 2, pp. 194–202, 2005.
[33]
K. Zendehdel, O. Nyren, C. G. ？Stenson, H. O. Adami, A. Ekbom, and W. Ye, “Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden,” Journal of the National Cancer Institute, vol. 95, no. 23, pp. 1797–1800, 2003.
[34]
G. D. Smith, D. Gunnell, and J. Holly, “Cancer and insulin-like growth factor-I. A potential mechanism linking the environment with cancer risk,” British Medical Journal, vol. 321, no. 7265, pp. 847–848, 2000.
[35]
J. M. P. Holly, D. J. Gunnell, and G. D. Smith, “Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer?” Journal of Endocrinology, vol. 162, no. 3, pp. 321–330, 1999.
[36]
H. Zhang, A. M. Pelzer, D. T. Kiang, and D. Yee, “Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin,” Cancer Research, vol. 67, no. 1, pp. 391–397, 2007.
[37]
K. Mardilovich, S. L. Pankratz, and L. M. Shaw, “Expression and function of the insulin receptor substrate proteins in cancer,” Cell Communication and Signaling, vol. 7, article 14, 2009.
[38]
M. R. Shen, Y. M. Hsu, K. F. Hsu, Y. F. Chen, M. J. Tang, and C. Y. Chou, “Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by αvβ3 integrin signaling,” Carcinogenesis, vol. 27, no. 5, pp. 962–971, 2006.
[39]
M. L. Macheda, S. Rogers, and J. D. Best, “Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer,” Journal of Cellular Physiology, vol. 202, no. 3, pp. 654–662, 2005.
[40]
H. Ulmer, W. Borena, K. Rapp et al., “Serum triglyceride concentrations and cancer risk in a large cohort study in Austria,” British Journal of Cancer, vol. 101, no. 7, pp. 1202–1206, 2009.
[41]
W. Borena, T. Stocks, H. Jonsson et al., “Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study,” Cancer Causes and Control, vol. 22, no. 2, pp. 291–299, 2011.
[42]
H. Iso, A. Ikeda, M. Inoue, S. Sato, and S. Tsugane, “Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts,” International Journal of Cancer, vol. 125, no. 11, pp. 2679–2686, 2009.
[43]
G. K. Reeves, K. Pirie, V. Beral, J. Green, E. Spencer, and D. Bull, “Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study,” British Medical Journal, vol. 335, no. 7630, pp. 1134–1139, 2007.
[44]
A. G. Renehan, M. Tyson, M. Egger, R. F. Heller, and M. Zwahlen, “Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies,” The Lancet, vol. 371, no. 9612, pp. 569–578, 2008.
[45]
E. E. Calle, C. Rodriguez, K. Walker-Thurmond, and M. J. Thun, “Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults,” New England Journal of Medicine, vol. 348, no. 17, pp. 1625–1638, 2003.
[46]
E. A. Lew and L. Garfinkel, “Variations in mortality by weight among 750,000 men and women,” Journal of Chronic Diseases, vol. 32, no. 8, pp. 563–576, 1979.
[47]
A. Wolk, G. Gridley, M. Svensson et al., “A prospective study of obesity and cancer risk (Sweden),” Cancer Causes and Control, vol. 12, no. 1, pp. 13–21, 2001.
[48]
H. Moller, A. Mellemgaard, K. Lindvig, and J. H. Olsen, “Obesity and cancer risk: a Danish record-linkage study,” European Journal of Cancer A, vol. 30, no. 3, pp. 344–350, 1994.
[49]
E. J. B. Ramos, Y. Xu, I. Romanova et al., “Is obesity an inflammatory disease?” Surgery, vol. 134, no. 2, pp. 329–335, 2003.
[50]
R. C. M. Van Kruijsdijk, E. Van Der Wall, and F. L. J. Visseren, “Obesity and cancer: the role of dysfunctional adipose tissue,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 10, pp. 2569–2578, 2009.
[51]
R. Baker, J. G. Dauner, A. C. Rodriguez et al., “Increased plasma levels of adipokines and inflammatory markers in older women with persistent HPV infection,” Cytokine, vol. 53, no. 3, pp. 282–285, 2011.
[52]
T. J. Kemp, A. Hildesheim, A. García-Pi？eres et al., “Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 8, pp. 1954–1959, 2010.
[53]
S. J. Bondy, J. C. Victor, and L. M. Diemert, “Origin and use of the 100 cigarette criterion in tobacco surveys,” Tobacco Control, vol. 18, no. 4, pp. 317–323, 2009.
[54]
S. M. Grundy, “Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy,” Nature Reviews Drug Discovery, vol. 5, no. 4, pp. 295–309, 2006.
[55]
D. T. Villareal, C. M. Apovian, R. F. Kushner, and S. Klein, “Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, the Obesity Society,” Obesity Research, vol. 13, no. 11, pp. 1849–1863, 2005.
[56]
S. J. McPhee, T. T. Nguyen, S. J. Shema et al., “Validation of recall of breast and cervical cancer screening by women in an ethnically diverse population,” Preventive Medicine, vol. 35, no. 5, pp. 463–473, 2002.
