Генетический профиль, метаболический синдром и риск развития рака молочной железы среди женщин Казахстана

  • D. Yerezhepov Назарбаев Университет, Казахстан, г. Астана
  • L. Manarbek Назарбаев Университет, Казахстан, г. Астана
  • А. Akilzhanova Назарбаев Университет, Казахстан, г. Астана

Аннотация

Работа посвящена исследованию связи рака молочной железы с метаболическим синдромом и генами, участвующими в метаболизме липидов. В рамках данного исследования нами были рекрутированы 136 участников с диагнозом РМЖ и 83 условно здоровых участников контрольной группы. Среди заболеваний, сопутствующих раку молочной железы, преобладают артериальная гипертензия, хронический бронхит, ишемическая болезнь сердца, миома матки, холецистит, варикозное расширение вен нижних конечностей, панкреатит. Встречаемость сахарного диабета 2-го типа составила 13,2%. Биохимический анализ на 18 метаболических показателей показал, что в группе больных по сравнению с контрольной группой уровень гомоцистеина и витамина В12 значительно превышает нормы. Анализ данных показал высокую корреляцию уровня гомоцистеина с риском развития рака молочной железы (ОШ = 15,29; ДИ = 5,67-41,28; р<0,001) в исследуемой группе. При исследовании ассоциации полиморфизмов исследуемых генов с риском развития РМЖ среди женщин Казахстана выявлено протективное воздействие в генах FTO, PRKAA2 и STK11. В случае гена CRTC2 в сверх доминантной модели выявлена ассоциация с риском развития РМЖ (ОШ=1,95; ДИ = 1,1-3,46; р=0,021). При исследовании связи между генетическим профилем и метаболическими показателями было выявлено, что генотип С/С (дикий) гена PRKAA2 может влиять на увеличение уровня холестерина при нормальных показателях витамина В12 (ОШ=3,43; ДИ = 1,25-9,39: р<0.015) и генотип Т/С влиять на увеличение холестерина при повышенных показателях витамина В12 (ОШ=3,23; ДИ = 1,1-9,52: р<0.035). Из данных анализа следует, что уровень гомоцистеина может быть использован как биомаркер, входящий в состав комплекса диагностических мер при раке молочной железы. К тому же, генотипы С/С и Т/С гена PRKAA2 могут быть использованы как маркеры уровней холестерина и витамина В12 в организме. Для исследования ассоциации других генов с биохимическими показателями и риском развития РМЖ необходимо увеличение выборки.
Ключевые слова: рак молочной железы, метаболический синдром, генетический профиль.

Литература

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References
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2 de Waard F., Baanders van Halewijn E.A. (1974) A prospective study in general practice on breast cancer risk in postmenopausal women. International Journal of Cancer, vol. 14, no. 2. pp. 153–160.
3 Esposito K., Chiodini P., Capuano A. et al. (2013) Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause, vol. 20, no. 12. pp. 1301–1309.
4 Fei X. and Michels K.B. (2007) Diabetes, metabolic syndrome and breast cancer: a review of the current evidence. Am. J. Clin. Nutr., vol. 86. pp. 823-835.
5 Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, vol. 136, no. 5, pp. e359-86. doi: 10.1002/ijc.29210.
6 Ferroni P., Palmirotta R., Martini F., Riondino S., Savonarola A., Spila A., Ciatti F., Sini V., Mariotti S., Del Monte G., Roselli M., Guadagni F. (2009) Determinants of homocysteine levels in colorectal and breast cancer patients. Anticancer Res., vol. 29, no. 10. pp. 4131-4138.
7 Ganguly P., Alam S.F. (2015) Role of homocysteine in the development of cardiovascular disease. Nurt. J., vol. 14, no. 6. doi: 10.1186/1475-2891-14-6.
8 Goldberg J.E., Schwertfeger K.L. (2010) Proinflammatory cytokines in breast cancer: mechanisms of action and potential targets for therapeutics. Current Drug Targets, vol. 11, no. 9. pp. 1133–1146.
9 Grundy S.M., Brewer H.B. Jr., Cleeman J.I., Smith S.C. Jr., Lenfant C. (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation, vol. 109, no. 3. pp. 433–438.
10 Grundy S.M. (2008) Metabolic syndrome pandemic. Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28. pp. 629–636.
11 Harvie M., Hooper L., Howell A.H. (2003) Central obesity and breast cancer risk: a systematic review. Obesity Reviews, vol. 4, no. 3. pp. 157–173.
12 Horikoshi M., Hara K., Ohashi J., Miyake K., Tokunaga K., Ito Ch., Kasuga M., Nagai R., Kadowaki T. (2006) A Polymorphism in the AMPK2 Subunit Gene Is Associated With Insulin Resistance and Type 2 Diabetes in the Japanese Population. Diabetes, vol. 55. pp. 919 –923.
13 Howlader N. National Cancer Institute. Breast Cancer Risk Factors. http://www.cancer.gov/ cancertopics/wyntk/breast/page4.
14 https://www.nur.kz/945272-sovremennoe-sostoyanie-problemy-serd.html.
15 Jarde T., Perrier S., Vasson M.P. (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. European Journal of Cancer, vol. 47, no. 1. pp. 33–43.
16 King M.W. AMPK: Master Metabolic Regulator. Medical Biochemistry. http://themedicalbioche- mistry page.org/ampk.php.
17 Largent J.A., McEligot A.J., Ziogas A. (2006) Hypertension, diuretics and breast cancer risk. Journal of Human Hypertension, vol. 20, no. 10. pp. 727–732.
18 Liao S., Li J., Wei W. (2011) Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pacific Journal of Cancer Prevention, vol. 12, no. 4. pp. 1061–1065.
19 Michels K.B., Solomon C.G., Hu F.B. et al. (2003) Type 2 diabetes and subsequent incidence of breast cancer in the nurses' health study. Diabetes Care, vol. 26, no. 6. pp. 1752–1758.
20 Mink P.J., Shahar E., Rosamond W.D. et al. (2002) Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study. The American Journal of Epidemiology, vol. 156, no. 4. pp. 349–352.
21 Motoshima H., Goldstein B.J., Igata M., Araki E. (2006) AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancer. J. Physiol., vol. 574. pp. 63–71.
22 Osaki Y., Taniguchi S.I., Tahara A., Okamoto M., Kishimoto T. (2012) Metabolic syndrome and incidence of liver and breast cancers in Japan. Cancer Epidemiology, vol. 36, no. 2. pp. 141–147.
23 Reaven G. M. (1988) Role of insulin resistance in human disease. Diabetes, vol. 37, no. 12. pp. 1595–1607.
24 Rosato V., Bosetti C., Talamini R. et al. (2011) Metabolic syndrome and the risk of breast cancer in postmenopausal women. Annals of Oncology, vol. 22, no. 12, pp. 2687–2692.
25 Rose D.P., Haffner S.M., Baillargeon J. (2007) Adiposity, the metabolic syndrome, and breast cancer in African-American and white American women. Endocrine Reviews, vol. 28, no. 7. pp. 763–777.
26 Soler M., Chatenoud L., Negri E., Parazzini F., Franceschi S., La Vecchia C. (1999) Hypertension and hormone-related neoplasms in women. Hypertension, vol. 34, no. 2. pp. 320–325.
27 Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, vol. 106, no. 25, pp. 3143–3421.
28 Tornberg S.A., Holm L-E., Carstensen J.M. (1988) Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressure. Acta Oncologica, vol. 27, no. 1. pp. 31–37.
29 Ursin G., Longnecker M.P., Haile R.W. et al. (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology, vol. 6, no. 2. pp. 137–141.
30 van den Brandt P.A., Spiegelman D., Yaun S-S. et al. (2000) Pooled analysis of prospective cohort studies on height, weight and breast cancer risk. American Journal of Epidemiology, vol. 152, no. 6. pp. 514–527.
31 World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva, Switzerland: World Health Organization, 1999.
32 Zhang S.M., Willett W.C., Selhub J., Hunter D.J., Giovannucci E.L., Holmes M.D., Colditz G.A., Hankinson S.E. (2003) Plasma Folate, Vitamin B6, Vitamin B12, Homocysteine, and Risk of Breast Cancer. J. Natl. Cancer Inst., vol. 95, no. 5. pp. 373-380. doi: 10.1093/jnci/95.5.373.
Опубликована
2018-07-14
Как цитировать
YEREZHEPOV, D.; MANARBEK, L.; AKILZHANOVA, А.. Генетический профиль, метаболический синдром и риск развития рака молочной железы среди женщин Казахстана. Experimental Biology, [S.l.], v. 74, n. 1, p. 74-87, july 2018. ISSN 2617-7498. Доступно на: <http://bb.kaznu.kz/index.php/biology/article/view/1317>. Дата доступа: 16 dec. 2018
Раздел
МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА

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