Elevated Homocysteine, an Emerging Biomarker for Cervical Cancer, A Case-Controlled Study
DOI:
https://doi.org/10.12974/2309-6160.2017.04.1Keywords:
Biomarker, cervical cancer, homocysteine.Abstract
Background: Elevated homocysteine, an emerging biomarker for cervical cancer is amenable to treatment by cheap and effective nutritional interventions.
Methods: From April 2012 through September 2012, a case-controlled study was performed in the Gynae oncology unit of Bangabandhu Sheikh Mujib Medical University (BSMMU) and the National Institute of Cancer Research and Hospital (NICR & H), in Dhaka, Bangladesh. The objectives were to measure the serum homocysteine levels in women with squamous cell carcinoma of the cervix and in normal controls. Fifty women with invasive squamous cell carcinoma and 50 normal controls were compared for demographic and socioeconomic differences. Blood was tested for homocysteine levels.
Results: Among cases of cervical cancer, 82% had homocysteine level between 4.5-15 µmol/L & 14% had high homocysteine level (>15 µmol/L). Whereas in control group, 98% had homocysteine level between 4.5-15 µmol/L and 2% had homocysteine <4.5 µmol/L (low). High level of homocysteine (>15 µmol/L) was not observed in any patient in the control group. The mean homocysteine level in cervical cancer patients was also higher (10.88 ?mol/L) than that of controls (8.50 µmol/L) and this difference was statistically significant.
Histological grade and clinical stage of cervical cancer did not correlate with serum homocysteine level.
Conclusion: There is a difference in homocysteine levels in women with cervical cancer. Homocysteine, which is associated with nutritional deficiencies of fruits and vegetables, may play a role as a marker for or as a co-factor in malignant transformation of cervical squamous epithelium. Larger studies are needed to further study this association. However public awareness is important regarding the role of fresh vegetables and fruits containing vitamin B (folate-vitamin B9; vitamin B12; vitamin B6) to reduce homocysteine and its possible consequences of cancer prevention.
References
Decherney H A, Nathan L, GooDwin MT, Laufer N. Current diagnosis and treatment, Obstetrics and Gynaecology. 10th ed. New York: McGraw-Hill Companies: 2007; pp. 834-45.
Rock LC, Moskowitz A, Huizar B, Saenz CC, Clark TJ, Daly TL, et al. High vegetable and fruit diet intervention in premenopaisal women with cervical intraepithelial neoplasia. Journal of the American dietetic association 2001; 101: 1167- 74. https://doi.org/10.1016/S0002-8223(01)00286-3
Keri Marshall ND. Cervical Dysplasia: Early Inervention. Alternative Medicine Review 2003; 8(2): 156-70.
Powers H J. Interaction among Folate, Riboflavin, Genotype, and Cancer, with reference to colorectal and cervical cancer. J Nutr 2005; 135: 2960s-2966s.
Garcia-Closas R, Castellsagud X, Bosch X, Gonzalez CA. The role of diet and nutrition in cervical carcinogenesis: a review of recent evidence. Int J Cancer 2005; 117: 629-37.
Weinstein SJ, Ziegler RG, Selhub J, Fears TR, Strickler HD, Brinton LA, et al. Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women. Cancer Causes Control 2001; 12: 317-24.
Ziegler RG, Weinstein SJ, Fears TR. Nutritional and genetic inefficiencies in one-carbon metabolism and cervical cancer risk. J Nutr 2002; 132: 23455-95.
Kohaar I, Kumar J, Thakur N, Hussain S, Niyaz MK, Das BC. Homocysteine levels are associated with cervical cancer independent of methylene tetrahydrofolate reductase gene (MTHFR) polymorphisms in Indian population. Biomarkers 2010; 15(1): 61-68. https://doi.org/10.3109/13547500903295881
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. Case–control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer (Phila) 2000; 89: 376-82. https://doi.org/10.1002/1097-0142(20000715)89:2<376::AIDCNCR24> 3.0.CO;2-O
Thomson SW, Heimburger DC, Cornwell PE, Turner ME, Sauberlich HE, Fox LM, et al. Effect of total plasma homocysteine on cervical dysplasia risk. Nutr Cancer 2000; 37(2): 128-33. https://doi.org/10.1207/S15327914NC372_2
Kwasirvewska A, Tukendorf A, Charzewska J, Semczuk M. Content of folic acid and free homocysteine in blood serum of human papillomavirus infected women with cervical dysplasia. Eur J Gynecol Oncol 2002; 23(4): 311-6.
Butterworth CE. Effect of total plasma homocysteine on cervical dyspalsia risk. Nutr Cancer 2000; 37: 128-33. https://doi.org/10.1207/S15327914NC372_2
Duttagupta C, Sengupta S, Roy M, Sengupta D, Chakraborty S, Bhattacharya P, et al. Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India. Eur J Cancer Prev 2002; 11: 447-56. https://doi.org/10.1097/00008469-200210000-00007
Jeffcoate. Jeffcoate’s Principles of Gynaecology. Revised and updated by Pratap Kumar and Narendra Malhotra. 7th edition. New Delhi: Arnold; 2008; pp. 467-68.
Yilmaz N, Kepkep N, Ciqek HK, Celik A, Meram I. Relation of parity and homocysteine to bone mineral density of postmenopausal women. Clin Lab 2006; 52(1-2): 49-56.
Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217-246. https://doi.org/10.1146/annurev.nutr.19.1.217
Alberg AJ, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ. The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiology Biomarkers and Prevention 2000; 9: 761-4
Sedjo RL, Fowler BM, Schneider A, Henning SM, Hatch K, Giuliano AR. Folate, vitamin B12, and homocysteine status. Findings of no relation between human papillomavirus persistence and cervical dysplasia. Nutrition 2003; 9(6): 497- 502. https://doi.org/10.1016/S0899-9007(02)01096-1
