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  2. Vol 4, No 2 (2022)
  3. Gitimu

CLSI Guided Reference Interval Limits for Cancer Biomarkers for Adults and Geriatrics

Richard M. Gitimu, Stanley K. Waithaka, Joseph K. Gikunju, Eliud N. M. Njagi

Abstract


Reference interval limits for cancer biomarkers in geriatrics are rare because priority is given to the development of reference interval limits for those in the age range of 18–60 years, which are normally used for clinical trials study. The aim of this study was therefore to develop gender and age-specific reference interval limits for cancer markers CA19-9, CEA, CA 15-3, CA 125, and PSA for adults and geriatrics in Taita-Taveta County, Kenya, using the CLSI CA28-A3 guideline. This prospective cross-sectional study involved 244 healthy referents, including 124 females and 120 males of ages 50–95, between May 2015 and December 2017 at the Department of Clinical Chemistry of Moi Subcounty Hospital, Voi, Kenya. Serum CA 19-9, CEA, CA 15-3, CA 125, and PSA of the 244 referents were measured using a well-calibrated, quality controlled Clinical Chemistry AutoAnalyzer. Gender differences in the measured values of the biomarkers were assessed using the Mann-Whitney U test, while age differences were assessed using the Kruskal-Wallis H test followed by the Mann-Whitney U test with an adjusted significant ρ-value of less than 0.0167. Reference interval limits for the measured cancer biomarkers were expressed in terms of medians and ranged between 2.5 and 97.5 percentiles. The established 95% reference interval limits were: 0-58 U/mL males and 0-42.8 U/mL females for CA 19–9, 0–7 ng/mL for CEA, 0-56.9 U/mL for CA 15–3, 0–25 ng/mL for CA 125, and 0–6.8 ng/mL for PSA. Gender-related biomarker values were developed for CA 19-9 adults and geriatrics (60–70 years), CEA for geriatrics (60–70 years), and CA 15-3 for adults. Age-related biomarker values were developed for CA 19–9 males and not for females. In conclusion, gender-related 95% reference interval limits were developed for CA 19-9, CEA, CA 15-3, CA 125, and PSA, and age-related 95% reference interval limits were established for CA 19-9. CA 19-9 decreased from adulthood to the early elderly and increased in the more elderly population. These developed reference interval limits for these biomarkers, which differed from those reported in previous literature, could be adopted for use in Taita-Taveta County, Kenya, for better medical care.

 

Doi: 10.28991/SciMedJ-2022-04-02-04

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Keywords


Geriatric; Cancer Markers; Reference Intervals; Taita Taveta; Kenya.

References


EP28-A3C. (2008). Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline (3rd Ed.). Clinical and Laboratory Standards Institute, Wayne, United States.

Chen, F., Shen, J., Wang, J., Cai, P., & Huang, Y. (2018). Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors. Cancer Management and Research, 10, 1313. doi:10.2147/CMAR.S155693.

Vestergaard, E. M., Hein, H. O., Meyer, H., Grunnet, N., Jørgensen, J., Wolf, H., & Ørntoft, T. F. (1999). Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clinical Chemistry, 45(1), 54–61.

Bjerner, J., Høgetveit, A., Wold Akselberg, K., Vangsnes, K., Paus, E., Bjøro, T., Børmer, O. P., & Nustad, K. (2008). Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, Alfa‐foeto‐protein (AFP), neuron‐specific enolase (NSE) and CA19.9 from the NORIP study. Scandinavian Journal of Clinical and Laboratory Investigation, 68(8), 703–713. doi:10.1080/00365510802126836.

Qin, X., Lin, L., Mo, Z., Lv, H., Gao, Y., Tan, A., Yang, X., Li, S., & Zhao, J. (2011). Reference Intervals for Serum Alpha-Fetoprotein and Carcinoembryonic Antigen in Chinese Han Ethnic Males from the Fangchenggang Area Male Health and Examination Survey. The International Journal of Biological Markers, 26(1), 65–71. doi:10.5301/jbm.2011.6364.

Zhang, G. M., Guo, X. X., Ma, X. B., & Zhang, G. M. (2016). Reference intervals of alpha-fetoprotein and carcinoembryonic antigen in the apparently healthy population. Medical Science Monitor, 22, 4875–4880. doi:10.12659/MSM.901861.

Cho, J. S., Kim, C. I., Do Hwan Seong, H. S. K., Kim, Y. S., Kim, S. J., Cho, I. R., ... & Chung, B. H.. (2005). Relationship between serum prostate-specific antigen and prostate volume in men with benign prostatic hyperplasia from multicenter study. Korean journal of urology, 46(8), 792-798.

Luboldt, H.-J., Schindler, J. F., & Rübben, H. (2007). Age-Specific Reference Ranges for Prostate-Specific Antigen as a Marker for Prostate Cancer. EAU-EBU Update Series, 5(1), 38–48. doi:10.1016/j.eeus.2006.10.003.

Khezri, A. A., Shirazi, M., Ayatollahi, S. M. T., Lotfi, M., Askarian, M., Ariafar, A., & Afrasiabi, M. A. (2009). Age specific reference levels of serum prostate-specific antigen, prostate volume and prostate specific antigen density in healthy Iranian men. Iranian Journal of Immunology, 6(1), 40–48.

Park, Y., Kim, Y., Lee, E. Y., Lee, J. H., & Kim, H. S. (2012). Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer. International Journal of Cancer, 130(5), 1136–1144. doi:10.1002/ijc.26129.

Liu, X., Wang, J., Zhang, S. X., & Lin, Q. (2013). Reference ranges of age-related prostate-specific antigen in men without cancer from Beijing area. Iranian Journal of Public Health, 42(11), 1216–1222.

Rahman, M. T., Sajani, T. T., Sultana, R., Choudhury, S. R., & Siddiqui, M. M. R. (2014). Prostate Specific Antigen (PSA): Normal Reference Value in Bangladeshi Male, a Retrospective PSA Analysis of 765 Male. Anwer Khan Modern Medical College Journal, 5(1), 19–22. doi:10.3329/akmmcj.v5i1.18766.

Slev, P. R., Rawlins, M. L., & Roberts, W. L. (2006). Performance Characteristics of Seven Automated CA 15-3 Assays. American Journal of Clinical Pathology, 125(5), 752–757. doi:10.1309/g6x6pr7526fakv0e.

Hayes, D. F., Zurawski, V. R., & Kufe, D. W. (1986). Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer. Journal of Clinical Oncology, 4(10), 1542–1550. doi:10.1200/JCO.1986.4.10.1542.

Duffy, M. J. (1999). CA 15-3 and related mucins as circulating markers in breast cancer. Annals of Clinical Biochemistry, 36(5), 579–586. doi:10.1177/000456329903600503.

Rubin, J. B., Lagas, J. S., Broestl, L., Sponagel, J., Rockwell, N., Rhee, G., Rosen, S. F., Chen, S., Klein, R. S., Imoukhuede, P., & Luo, J. (2020). Sex differences in cancer mechanisms. Biology of Sex Differences, 11(1). doi:10.1186/s13293-020-00291-x.

Zhang, G. M., Bai, S. M., Zhang, G. M., & Ma, X. B. (2018). Reference intervals of carbohydrate antigen 19-9 in the apparently healthy adult population. Journal of Clinical Laboratory Analysis, 32(5). doi:10.1002/jcla.22380.

La’ulu, S. L., & Roberts, W. L. (2007). Performance characteristics of five automated CA 19-9 assays. American Journal of Clinical Pathology, 127(3), 436–440. doi:10.1309/H52VET3M6P7GYWG1.

Pauler, D. K., Menon, U., McIntosh, M., Symecko, H. L., Skates, S. J., & Jacobs, I. J. (2001). Factors influencing serum ca125ii levels in healthy postmenopausal women. Cancer Epidemiology Biomarkers and Prevention, 10(5), 489–493.


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DOI: 10.28991/SciMedJ-2022-04-02-04

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Copyright (c) 2022 RICHARD GITIMU, DR LAWRENCE WAITHAKA, JOSEPH GIKUNJU, ELIUD NJAGI