Pre-Diagnostic Circulating Resistin Concentrations Are Not Associated with Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. The European Prospective Investigation into Cancer and Nutrition Study
2.1.1. Study Population
2.1.2. Assessments of Anthropometry, Lifestyle Factors, and Dietary Exposure
2.1.3. Blood Collection
2.1.4. Follow-Up for Cancer Incidence
2.2. The Nested Case-Control Study
2.2.1. Study Design
2.2.2. Laboratory Analysis
2.2.3. Final Dataset, Handling of Missing Data
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Disclaimer
References
- Steppan, C.M.; Bailey, S.T.; Bhat, S.; Brown, E.J.; Banerjee, R.R.; Wright, C.M.; Patel, H.R.; Ahima, R.S.; Lazar, M.A. The hormone resistin links obesity to diabetes. Nature 2001, 409, 307–312. [Google Scholar] [CrossRef]
- Savage, D.B.; Sewter, C.P.; Klenk, E.S.; Segal, D.G.; Vidal-Puig, A.; Considine, R.V.; O’Rahilly, S. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator–activated receptor-γ action in humans. Diabetes 2001, 50, 2199–2202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Patel, L.; Buckels, A.C.; Kinghorn, I.J.; Murdock, P.R.; Holbrook, J.D.; Plumpton, C.; Macphee, C.H.; Smith, S.A. Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem. Biophys. Res. Commun. 2003, 300, 472–476. [Google Scholar] [CrossRef]
- Degawa-Yamauchi, M.; Bovenkerk, J.E.; Juliar, B.E.; Watson, W.; Kerr, K.; Jones, R.; Zhu, Q.; Considine, R.V. Serum resistin (FIZZ3) protein is increased in obese humans. J. Clin. Endocrinol. Metab. 2003, 88, 5452–5455. [Google Scholar] [CrossRef] [PubMed]
- Ho, G.Y.; Wang, T.; Gunter, M.J.; Strickler, H.D.; Cushman, M.; Kaplan, R.C.; Wassertheil-Smoller, S.; Xue, X.; Rajpathak, S.N.; Chlebowski, R.T. Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer Res. 2012, 72, 3029–3037. [Google Scholar] [CrossRef] [Green Version]
- Konigorski, S.; Janke, J.; Drogan, D.; Bergmann, M.M.; Hierholzer, J.; Kaaks, R.; Boeing, H.; Pischon, T. Prediction of circulating adipokine levels based on body fat compartments and adipose tissue gene expression. Obes. Facts 2019, 12, 590–605. [Google Scholar] [CrossRef]
- Zuniga, M.C.; Raghuraman, G.; Hitchner, E.; Weyand, C.; Robinson, W.; Zhou, W. PKC-epsilon and TLR4 synergistically regulate resistin-mediated inflammation in human macrophages. Atherosclerosis 2017, 259, 51–59. [Google Scholar] [CrossRef] [Green Version]
- Codoñer-Franch, P.; Alonso-Iglesias, E. Resistin: Insulin resistance to malignancy. Clin. Chim. Acta 2015, 438, 46–54. [Google Scholar] [CrossRef]
- Filková, M.; Haluzík, M.; Gay, S.; Šenolt, L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin. Immunol. 2009, 133, 157–170. [Google Scholar] [CrossRef] [Green Version]
- Bokarewa, M.; Nagaev, I.; Dahlberg, L.; Smith, U.; Tarkowski, A. Resistin, an adipokine with potent proinflammatory properties. J. Immunol. 2005, 174, 5789–5795. [Google Scholar] [CrossRef] [Green Version]
- Lehrke, M.; Reilly, M.P.; Millington, S.C.; Iqbal, N.; Rader, D.J.; Lazar, M.A. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004, 1, e45. [Google Scholar] [CrossRef] [PubMed]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Arnold, M.; Sierra, M.S.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017, 66, 683–691. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sawicki, T.; Ruszkowska, M.; Danielewicz, A.; Niedźwiedzka, E.; Arłukowicz, T.; Przybyłowicz, K.E. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers 2021, 13, 2025. [Google Scholar] [CrossRef]
- Clinton, S.K.; Giovannucci, E.L.; Hursting, S.D. The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on diet, nutrition, physical activity, and cancer: Impact and future directions. J. Nutr. 2020, 150, 663–671. [Google Scholar] [CrossRef]
- Nimptsch, K.; Konigorski, S.; Pischon, T. Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine. Metabolism 2019, 92, 61–70. [Google Scholar] [CrossRef]
- Yang, G.; Fan, W.; Luo, B.; Xu, Z.; Wang, P.; Tang, S.; Xu, P.; Yu, M. Circulating resistin levels and risk of colorectal cancer: A meta-analysis. BioMed Res. Int. 2016, 2016. [Google Scholar] [CrossRef] [Green Version]
- Zhou, B.; Shu, B.; Yang, J.; Liu, J.; Xi, T.; Xing, Y. C-reactive protein, interleukin-6 and the risk of colorectal cancer: A meta-analysis. Cancer Causes Control. 2014, 25, 1397–1405. [Google Scholar] [CrossRef]
- Bernstein, C.N.; Blanchard, J.F.; Kliewer, E.; Wajda, A. Cancer risk in patients with inflammatory bowel disease: A population-based study. Cancer 2001, 91, 854–862. [Google Scholar] [CrossRef]
- Riboli, E.; Hunt, K.; Slimani, N.; Ferrari, P.; Norat, T.; Fahey, M.; Charrondiere, U.; Hemon, B.; Casagrande, C.; Vignat, J.; et al. European Prospective Investigation into Cancer and Nutrition (EPIC): Study populations and data collection. Public Health Nutr. 2002, 5, 1113–1124. [Google Scholar] [CrossRef] [Green Version]
- Haftenberger, M.; Lahmann, P.H.; Panico, S.; Gonzalez, C.A.; Seidell, J.C.; Boeing, H.; Giurdanella, M.C.; Krogh, V.; Bueno-de-Mesquita, H.B.; Peeters, P.H.M.; et al. Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr. 2002, 5, 1147–1162. [Google Scholar] [CrossRef] [PubMed]
- Wareham, N.J.; Jakes, R.W.; Rennie, K.L.; Schuit, J.; Mitchell, J.; Hennings, S.; Day, N.E. Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr. 2003, 6, 407–413. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aleksandrova, K.; Boeing, H.; Jenab, M.; Bueno-de-Mesquita, H.B.; Jansen, E.; van Duijnhoven, F.J.; Fedirko, V.; Rinaldi, S.; Romieu, I.; Riboli, E.; et al. Total and high-molecular weight adiponectin and risk of colorectal cancer: The European Prospective Investigation into Cancer and Nutrition Study. Carcinogenesis 2012, 33, 1211–1218. [Google Scholar] [CrossRef] [PubMed]
- Aleksandrova, K.; Boeing, H.; Jenab, M.; Bueno-de-Mesquita, H.B.; Jansen, E.; Van Duijnhoven, F.J.; Rinaldi, S.; Fedirko, V.; Romieu, I.; Riboli, E.; et al. Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Cancer Res. 2012, 72, 5328–5337. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leufkens, A.M.; Van Duijnhoven, F.J.; Woudt, S.H.; Siersema, P.D.; Jenab, M.; Jansen, E.H.; Pischon, T.; Tjønneland, A.; Olsen, A.; Overvad, K.; et al. Biomarkers of oxidative stress and risk of developing colorectal cancer: A cohort-nested case-control study in the European Prospective Investigation into Cancer and Nutrition. Am. J. Epidemiol. 2012, 175, 653–663. [Google Scholar] [CrossRef] [Green Version]
- Jenab, M.; Riboli, E.; Cleveland, R.J.; Norat, T.; Rinaldi, S.; Nieters, A.; Biessy, C.; Tjønneland, A.; Olsen, A.; Overvad, K.; et al. Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition. Int. J. Cancer 2007, 121, 368–376. [Google Scholar] [CrossRef]
- Aleksandrova, K.; Jenab, M.; Boeing, H.; Jansen, E.; Bueno-de-Mesquita, H.B.; Rinaldi, S.; Riboli, E.; Overvad, K.; Dahm, C.C.; Olsen, A.; et al. Circulating C-reactive protein concentrations and risks of colon and rectal cancer: A nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Am. J. Epidemiol. 2010, 172, 407–418. [Google Scholar] [CrossRef]
- Rinaldi, S.; Rohrmann, S.; Jenab, M.; Biessy, C.; Sieri, S.; Palli, D.; Tumino, R.; Mattiello, A.; Vineis, P.; Nieters, A.; et al. Glycosylated hemoglobin and risk of colorectal cancer in men and women, the European prospective investigation into cancer and nutrition. Cancer Epidemiol. Prev. Biomark. 2008, 17, 3108–3115. [Google Scholar] [CrossRef] [Green Version]
- Asuero, A.G.; Sayago, A.; Gonzalez, A. The correlation coefficient: An overview. Crit. Rev. Anal. Chem. 2006, 36, 41–59. [Google Scholar] [CrossRef]
- Fargnoli, J.L.; Fung, T.T.; Olenczuk, D.M.; Chamberland, J.P.; Hu, F.B.; Mantzoros, C.S. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses’ Health Study. Am. J. Clin. Nutr. 2008, 88, 1213–1224. [Google Scholar] [CrossRef]
- Iqbal, N.; Seshadri, P.; Stern, L.; Loh, J.; Kundu, S.; Jafar, T.; Samaha, F. Serum resistin is not associated with obesity or insulin resistance in humans. Eur. Rev. Med. Pharmacol. Sci. 2005, 9, 161–165. [Google Scholar] [PubMed]
- Grund, B.; Sabin, C. Analysis of biomarker data: Logs, odds ratios and ROC curves. Curr. Opin. HIV AIDS 2010, 5, 473–479. [Google Scholar] [CrossRef] [PubMed]
- Shannon, D. Box-and-whisker plots with the SAS System®, 2003. Pharm. Stat. 2003, 2, 291–294. [Google Scholar] [CrossRef]
- Dupont, W.D. Power calculations for matched case-control studies. Biometrics 1988, 44, 1157–1168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, J.H.; Chan, J.L.; Yiannakouris, N.; Kontogianni, M.; Estrada, E.; Seip, R.; Orlova, C.; Mantzoros, C.S. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: Cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J. Clin. Endocrinol. Metab. 2003, 88, 4848–4856. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weikert, C.; Westphal, S.; Luley, C.; Willich, S.N.; Boeing, H.; Pischon, T. Within-subject variation of plasma resistin levels over a 1-year period. Clin. Chem. Lab. Med. 2007, 45, 899–902. [Google Scholar] [CrossRef]
- Mihajlovic, M.; Ninic, A.; Sopic, M.; Miljkovic, M.; Stefanovic, A.; Vekic, J.; Spasojevic-Kalimanovska, V.; Zeljkovic, D.; Trifunovic, B.; Stjepanovic, Z.; et al. Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: A multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine. EPMA J. 2019, 10, 307–316. [Google Scholar] [CrossRef] [Green Version]
- Otake, S.; Takeda, H.; Fujishima, S.; Fukui, T.; Orii, T.; Sato, T.; Sasaki, Y.; Nishise, S.; Kawata, S. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer. World J. Gastroenterol. 2010, 16, 1252–1257. [Google Scholar] [CrossRef]
- Joshi, R.K.; Kim, W.J.; Lee, S.-A. Association between obesity-related adipokines and colorectal cancer: A case-control study and meta-analysis. World J. Gastroenterol. 2014, 20, 7941–7949. [Google Scholar] [CrossRef]
- Danese, E.; Montagnana, M.; Minicozzi, A.M.; Bonafini, S.; Ruzzenente, O.; Gelati, M.; De Manzoni, G.; Lippi, G.; Guidi, G.C. The role of resistin in colorectal cancer. Clin. Chim. Acta 2012, 413, 760–764. [Google Scholar] [CrossRef]
- Nakajima, T.E.; Yamada, Y.; Hamano, T.; Furuta, K.; Matsuda, T.; Fujita, S.; Kato, K.; Hamaguchi, T.; Shimada, Y. Adipocytokines as new promising markers of colorectal tumors: Adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer. Cancer Sci. 2010, 101, 1286–1291. [Google Scholar] [CrossRef] [PubMed]
- Wågsäter, D.; Mumtaz, M.; Löfgren, S.; Hugander, A.; Dimberg, J. Resistin in human colorectal cancer: Increased expression independently of resistin promoter −420C> G genotype. Cancer Investig. 2008, 26, 1008–1014. [Google Scholar] [CrossRef] [PubMed]
- Weikert, C.; Westphal, S.; Berger, K.; Dierkes, J.; Möhlig, M.; Spranger, J.; Rimm, E.B.; Willich, S.N.; Boeing, H.; Pischon, T. Plasma resistin levels and risk of myocardial infarction and ischemic stroke. J. Clin. Endocrinol. Metab. 2008, 93, 2647–2653. [Google Scholar] [CrossRef]
- Malo, E.; Ukkola, O.; Jokela, M.; Moilanen, L.; Kähönen, M.; Nieminen, M.S.; Salomaa, V.; Jula, A.; Kesäniemi, Y.A. Resistin is an indicator of the metabolic syndrome according to five different definitions in the Finnish Health 2000 survey. Metab. Syndr. Relat. Disord. 2011, 9, 203–210. [Google Scholar] [CrossRef] [PubMed]
- Fargnoli, J.L.; Sun, Q.; Olenczuk, D.; Qi, L.; Zhu, Y.; Hu, F.B.; Mantzoros, C.S. Resistin is associated with biomarkers of inflammation while total and HMW adiponectin are associated with biomarkers of inflammation, insulin resistance, and endothelial function. Eur. J. Endocrinol. 2010, 162, 281–288. [Google Scholar] [CrossRef] [Green Version]
- Su, K.-Z.; Li, Y.-R.; Zhang, D.; Yuan, J.-H.; Zhang, C.-S.; Liu, Y.; Song, L.-M.; Lin, Q.; Li, M.-W.; Dong, J. Relation of circulating resistin to insulin resistance in type 2 diabetes and obesity: A systematic review and meta-analysis. Front. Physiol. 2019, 10, 1399. [Google Scholar] [CrossRef] [Green Version]
- Kaplan, R.C.; Ho, G.Y.; Xue, X.; Rajpathak, S.; Cushman, M.; Rohan, T.E.; Strickler, H.D.; Scherer, P.E.; Anastos, K. Within-individual stability of obesity-related biomarkers among women. Cancer Epidemiol. Biomark. Prev. 2007, 16, 1291–1293. [Google Scholar] [CrossRef] [Green Version]
- Bergmann, M.M.; Calle, E.E.; Mervis, C.A.; Miracle-McMahill, H.L.; Thun, M.J.; Health, C.W. Validity of self-reported cancers in a propsective cohort study in comparison with data from state cancer registries. Am. J. Epidemiol. 1998, 147, 556–562. [Google Scholar] [CrossRef]
Quartiles of Resistin Concentration | ||||
---|---|---|---|---|
Q1 (N = 324) | Q2 (N = 325) | Q3 (N = 321) | Q4 (N = 323) | |
Resistin quartile ranges (ng/mL) | 3.47 | 3.47< to 4.28 | 4.28< to 5.42 | 5.42< to 34.41 |
Age at blood collection, years, mean (SD) a | 57.6 (6.9) | 57.5 (7.2) | 58.1 (6.7) | 59 (7.1) |
Women, n (%) a | 154 (47.5) | 183 (56.3) | 157 (48.9) | 187 (57.9) |
Postmenopausal women, baseline, n (%) a | 123 (38.0) | 135 (41.5) | 116 (36.1) | 141 (43.7) |
Fasting (>6 h), n (%) a | 98 (30.2) | 98 (30.2) | 74 (23.1) | 80 (24.8) |
BMI, kg/m2, mean (SD) | 26.2 (3.5) | 26.6 (4.1) | 26.3 (3.8) | 26.2 (3.7) |
Waist circumference, cm, mean (SD) b | 89.2 (12.5) | 88.4 (12.2) | 88.8 (11.8) | 87.7 (12.6) |
Diagnosed diabetes at baseline (self-reported or HbA1C ≥ 6.5%), n (%) | 19 (5.9) | 18 (5.5) | 13 (4.0) | 14 (4.3) |
Current smoker, n (%) | 84 (25.9) | 86 (26.5) | 68 (21.2) | 85 (26.3) |
University degree or higher education level, n (%) | 68 (21) | 52 (16) | 51 (15.9) | 58 (18) |
Physically moderately active, or active, sex-specific, n (%) | 178 (54.9) | 176 (54.2) | 168 (52.3) | 195 (60.4) |
Alcohol abstainers (<0.3 g/day), n (%) | 38 (11.7) | 45 (13.8) | 43 (13.4) | 51 (15.8) |
Alcohol consumption, g/day, median (Q1–Q3) b | 10.6 (3.2–28.1) | 8.5 (1.6–23.5) | 7.7 (1.7–19.9) | 6.0 (1.0–16.8) |
Energy intake, Kcal/day, median (Q1–Q3) b | 2084 (1608–2478) | 2010 (1638–2404) | 2052 (1719–2511) | 1997 (1590–2464) |
Red meat, g/day, median (Q1–Q3) b | 43.4 (24.4–75.3) | 43.0 (25.3–69.9) | 49.6 (27.4–76.5) | 47.7 (24.2–74.9) |
Processed meat, g/day, median (Q1–Q3) b | 24.6 (13.0–42.6) | 23.3 (12.5–45.9) | 28.4 (16.8–44.3) | 23.2 (12.9–42.6) |
Dietary fiber, g/day, median (Q1–Q3) b | 23.6 (18.0–28.6) | 22.8 (18.0–27.5) | 23.2 (18.0–27.8) | 22.1 (17.9–26.7) |
Fruit intake, g/day, median (Q1–Q3) b | 191.5 (106.4–314.3) | 195.2 (108.2–330.2) | 176.9 (98.2–279.8) | 191.5 (109.3–318.4) |
Vegetable intake, g/day, median (Q1–Q3) b | 160.9 (104.3–230.8) | 166.8 (103.8–248.1) | 148.1 (96.0–221.6) | 157.9 (97.4–241.5) |
Dairy intake, g/day, median (Q1–Q3) b | 278.9 (155.2–435.3) | 310.6 (175.0–451.0) | 318.2 (171.2–495.9) | 305.9 (161.5–484.5) |
Fish and shellfish, g/day, median (Q1–Q3) b | 29.0 (13.4–52.3) | 29.7 (16.4–51.8) | 29.4 (14.2–49.3) | 30.0 (13.6–52.4) |
Adiponectin, µg/mL, median (Q1–Q3) b | 7.3 (5.2–10.1) | 7.3 (5.5–9.7) | 6.9 (5.0–9.2) | 7.2 (5.3–9.6) |
HMW adiponectin, µg/mL (Q1–Q3) b | 3.7 (2.4–5.7) | 3.8 (2.4–5.4) | 3.6 (2.2–5.1) | 3.7 (2.4–5.2) |
Leptin, ng/mL (Q1–Q3) b | 6.3 (3.4–14.1) | 9.4 (5.1–19.2) | 7.7 (3.5–16.6) | 6.9 (3.6–17.0) |
Soluble leptin receptor, ng/mL, mean (SD) b | 23 (8.9) | 21.9 (7.9) | 22.7 (8.6) | 23.6 (15.8) |
ROM, Carratelli units, mean (SD) b | 381 (71.8) | 382.4 (69.4) | 379.1 (64.2) | 397.4 (71.7) |
hsCRP, mg/L, median (Q1–Q3) b | 1.9 (0.8–3.7) | 2.2 (0.9–4.0) | 2.1 (0.9–4.2) | 2.9 (1.3–5.8) |
C-peptide, ng/mL, median (Q1–Q3) b | 3.6 (2.5–5.9) | 3.7 (2.6–5.6) | 4.0 (2.9–6.3) | 4.3 (2.9–5.9) |
HDL-C, mmol/L, median (Q1–Q3) b | 1.5 (1.2–1.8) | 1.5 (1.2–1.7) | 1.4 (1.2–1.7) | 1.4 (1.1–1.7) |
HbA1c, %, mean (SD) b | 5.8 (0.6) | 5.8 (0.8) | 5.7 (0.6) | 5.7 (0.5) |
Number of Participants | Correlation Coefficient (r) | p-Value | |
---|---|---|---|
BMI, kg/m2 | 1293 | −0.02 | 0.52 |
Waist circumference, cm | 1216 | −0.03 | 0.28 |
Adiponectin, µg/mL | 651 | −0.08 | 0.04 |
HMW adiponectin, µg/mL | 650 | −0.07 | 0.08 |
Leptin, ng/mL | 651 | −0.002 | 0.96 |
Soluble leptin receptor, ng/mL | 651 | −0.02 | 0.56 |
ROM, Carratelli units | 723 | 0.07 | 0.05 |
CRP-hs, mg/L | 727 | 0.12 | <0.01 |
C-peptide, ng/mL | 622 | 0.09 | 0.02 |
HDL-C, mmol/L | 726 | −0.12 | <0.01 |
HbA1c, % | 606 | −0.05 | 0.24 |
Quartile Form | Continuous Form | ||||||
---|---|---|---|---|---|---|---|
Q1 | Q2 | Q3 | Q4 | p-Trend a | Doubling Resistin Concentrations b | p-Value | |
Resistin quartile ranges (ng/mL) | 3.47 | 3.47< to 4.28 | 4.28< to 5.42 | 5.42< to 34.41 | |||
Colorectal Cancer | |||||||
No. cases/controls | 297/324 | 317/325 | 348/321 | 331/323 | 1293/1293 | ||
Model 1 | ref | 1.06 (0.85–1.32) | 1.19 (0.95–1.49) | 1.13 (0.90–1.41) | 0.46 | 1.11 (0.95–1.30) | 0.19 |
Model 2 | ref | 1.10 (0.88–1.37) | 1.22 (0.97–1.53) | 1.15 (0.91–1.46) | 0.38 | 1.12 (0.95–1.31) | 0.18 |
Model 3 | ref | 1.11 (0.88–1.39) | 1.21 (0.97–1.53) | 1.15 (0.91–1.46) | 0.41 | 1.11 (0.94–1.30) | 0.22 |
Colon Cancer | |||||||
No. cases/controls | 165/174 | 178/193 | 203/188 | 211/202 | 757/757 | ||
Model 1 | ref | 0.97 (0.73–1.30) | 1.16 (0.86–1.56) | 1.11 (0.83–1.50) | 0.62 | 1.14 (0.94–1.40) | 0.19 |
Model 2 | ref | 1.01 (0.75–1.37) | 1.17 (0.86–1.59) | 1.15 (0.84–1.56) | 0.67 | 1.15 (0.93–1.42) | 0.19 |
Model 3 | ref | 1.04 (0.76–1.41) | 1.20 (0.88–1.65) | 1.20 (0.88–1.65) | 0.53 | 1.18 (0.95–1.47) | 0.13 |
Rectal Cancer | |||||||
No. cases/controls | 120/134 | 119/115 | 127/118 | 109/108 | 475/475 | ||
Model 1 | ref | 1.15 (0.81–1.64) | 1.20 (0.85–1.71) | 1.13 (0.78–1.64) | 0.76 | 1.07 (0.82–1.39) | 0.62 |
Model 2 | ref | 1.17 (0.81–1.68) | 1.26 (0.88–1.82) | 1.20 (0.81–1.76) | 0.64 | 1.09 (0.83–1.43) | 0.55 |
Model 3 | ref | 1.16 (0.80–1.68) | 1.25 (0.86–1.80) | 1.17 (0.79–1.73) | 0.69 | 1.06 (0.80–1.41) | 0.66 |
Quartile Form | Continuous Form | ||||||
---|---|---|---|---|---|---|---|
Q1 | Q2 | Q3 | Q4 | p-Trend a | Doubling Resistin Concentrations b | p-Value | |
Resistin quartile ranges (ng/mL) | 3.47 | 3.47< to 4.28 | 4.28< to 5.42 | 5.42< to 34.41 | |||
Sex | |||||||
Women | |||||||
No. cases/controls | 134/154 | 165/183 | 190/157 | 192/187 | 681/681 | ||
RR (95% CI) | ref | 1.02 (0.75–1.40) | 1.39 (1.00–1.94) | 1.21 (0.87–1.67) | 0.17 | 1.06 (0.85–1.33) | 0.59 |
Postmenopausal women | |||||||
No. cases/controls | 97/120 | 123/129 | 136/110 | 135/132 | 491/491 | ||
RR (95% CI) | ref | 1.14 (0.79–1.63) | 1.48 (1.01–2.18) | 1.25 (0.85–1.84) | 0.25 | 1.12 (0.86–1.47) | 0.38 |
Men | |||||||
No. cases/controls | 163/170 | 152/142 | 158/164 | 139/136 | 612/612 | ||
RR (95% CI) | ref | 1.20 (0.85–1.69) | 1.05 (0.76–1.47) | 1.08 (0.76–1.54) | 0.77 | 1.14 (0.89–1.46) | 0.29 |
Sex and Tumor subsite | |||||||
Colon cancer women | |||||||
No. cases/controls | 77/93 | 99/108 | 120/103 | 133/125 | 429/429 | ||
RR (95% CI) | ref | 1.11 (0.73–1.68) | 1.40 (0.91–2.16) | 1.37 (0.89–2.11) | 0.37 | 1.17 (0.88–1.57) | 0.28 |
Colon cancer men | |||||||
No. cases/controls | 88/81 | 79/85 | 83/85 | 78/77 | 328/328 | ||
RR (95% CI) | ref | 0.96 (0.59–1.55) | 0.97 (0.60–1.59) | 0.95 (0.58–1.57) | 1.00 | 1.13 (0.80–1.58) | 0.50 |
Rectal cancer women | |||||||
No. cases/controls | 54/53 | 55/65 | 62/50 | 53/56 | 224/224 | ||
RR (95% CI) | ref | 0.70 (0.41–1.19) | 1.11 (0.62–2.00) | 0.72 (0.40–1.31) | 0.29 | 0.71 (0.46–1.08) | 0.11 |
Rectal cancer men | |||||||
No. cases/controls | 66/81 | 64/50 | 65/68 | 56/52 | 251/251 | ||
RR (95% CI) | ref | 1.89 (1.06–3.36) | 1.43 (0.85–2.40) | 1.8 (0.99–3.24) | 0.12 | 1.53 (1.01–2.33) | 0.05 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Pham, T.-T.; Nimptsch, K.; Aleksandrova, K.; Jenab, M.; Reichmann, R.; Wu, K.; Tjønneland, A.; Kyrø, C.; Schulze, M.B.; Kaaks, R.; et al. Pre-Diagnostic Circulating Resistin Concentrations Are Not Associated with Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study. Cancers 2022, 14, 5499. https://doi.org/10.3390/cancers14225499
Pham T-T, Nimptsch K, Aleksandrova K, Jenab M, Reichmann R, Wu K, Tjønneland A, Kyrø C, Schulze MB, Kaaks R, et al. Pre-Diagnostic Circulating Resistin Concentrations Are Not Associated with Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study. Cancers. 2022; 14(22):5499. https://doi.org/10.3390/cancers14225499
Chicago/Turabian StylePham, Thu-Thi, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Robin Reichmann, Kana Wu, Anne Tjønneland, Cecilie Kyrø, Matthias B. Schulze, Rudolf Kaaks, and et al. 2022. "Pre-Diagnostic Circulating Resistin Concentrations Are Not Associated with Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study" Cancers 14, no. 22: 5499. https://doi.org/10.3390/cancers14225499