Metabolic syndrome and breast cancer
In my last piece on Breast Cancer awareness, I referred to three pillars of the World Health Organisation (WHO) on the fight against breast cancer, namely, early detection, early diagnosis and comprehensive treatment of breast cancer (BC). I am still on breast cancer. Metabolic syndrome which is a public health concern is linked to the development of breast cancer. I will be using materials from a paper by Zhao et al. The Metabolic Syndrome Is a Risk Factor for Breast Cancer: A Systematic Review and Meta-Analysis. Obes Facts 2020; 13:384–396.
Breast cancer (BC) is a common malignancy of which the incidence ranks first in women. Breast cancer is the leading cause of tumour-related deaths in women and the fifth of that in the general population around the world. In Western countries, a woman’s lifetime risk of developing BC is 12 per cent. Asian countries have a lower prevalence than Western countries, but due to the shift of lifestyle to Western countries, it shows an increasing trend in recent years. Studies have found that the occurrence of BC was not only related to the traditional risk factors such as age, family history, birth history, and menstrual history, but also to obesity, diabetes, and dyslipidemia.
Metabolic syndrome
The metabolic syndrome (MetS) is a series of metabolic abnormalities characterised by insulin resistance, with main components including obesity, hyperglycemia, hyperinsulinemia, dyslipidemia, and hypertension, which promote the development and progression of type 2 diabetes and cardiovascular diseases. The concept and definition of MetS first appeared in 2001, and its content was constantly revised as research progressed. Due to ethnic differences and diagnostic criteria, MetS incidence varies widely from region to region. In developed countries, the incidence is 22–39 per cent. According to a survey by the National Health and Nutrition Examination Surveys in the United States, the incidence of MetS in people over 20 years is 31.9% (30.6% for men and 33.2% for women). A study conducted in China found an incidence of 27.4% (27.9% for men and 26.8% for women).
Definition
WHO 1999:
Presence of insulin resistance or glucose > 6.1 mmol/L (110 mg/dl), 2 h glucose > 7.8 mmol (140 mg/dl) (required) along with any two or more of the following:
1. HDL cholesterol < 0.9 mmol/L (35 mg/dl) in men, < 1.0 mmol/L (40 mg/dl) in women
2. Triglycerides > 1.7 mmol/L (150 mg/dl)
3. Waist/hip ratio > 0.9 (men) or > 0.85 (women) or BMI > 30 kg/m2
4. Blood pressure > 140/90 mmHg
NCEP (National Cholesterol Education Program) ATP3 2005:
Presence of any three or more of the following:
1. Blood glucose greater than 5.6 mmol/L (100 mg/dl) or drug treatment for elevated blood glucose
2. HDL cholesterol < 1.0 mmol/L (40 mg/dl) in men, < 1.3 mmol/L (50 mg/dl) in women or drug treatment for low HDL-C
3. Blood triglycerides > 1.7 mmol/L (150 mg/dl) or drug treatment for elevated triglycerides
4. Waist > 102 cm (men) or > 88 cm (women)
5. Blood pressure > 130/85 mmHg or drug treatment for hypertension
IDF (International Diabetes Federation) 2006:
Waist > 94 cm (men) or > 80 cm (women) along with the presence of two or more of the following:
1. Blood glucose greater than 5.6 mmol/L (100 mg/dl) or diagnosed diabetes
2. HDL cholesterol < 1.0 mmol/L (40 mg/dl) in men, < 1.3 mmol/L (50 mg/dl) in women or drug treatment for low HDL-C
3. Blood triglycerides > 1.7 mmol/L (150 mg/dl) or drug treatment for elevated triglycerides
4. Blood pressure > 130/85 mmHg or drug treatment for hypertension
Note: NCEP and IDF definition are very similar except in the waist parameter of 102 vs. 94 cm in men and 88 vs. 80 cm in women.
Public health
MetS has gradually become a public health problem in countries with high obesity and Western diet patterns. Studies have shown that the incidence and mortality of cardiovascular diseases in people who fulfill the diagnostic criteria is about 2–3 times higher than in those without MetS.
Recently, MetS has been found to be associated with the pathogenesis and prognosis of various malignant tumors. Many studies have also confirmed that multiple components of MetS are closely related to the occurrence and development of BC. The main components (central obesity, hyperglycemia, dyslipidemia, and hypertension) can affect the occurrence and prognosis of BC through various mechanisms. The link between Mets and BC appears to be stronger in menopausal women.
Mechanisms
The mechanism by which MetS increase the incidence of BC is still under exploration. Insulin resistance may be one of the reasons. Insulin is the main hormone that stimulates cell proliferation, and it directly promotes the proliferation of breast tissue and tumor cells, thus possibly promoting BC incidence. Besides, insulin promotes tumor cell proliferation by upregulating insulin-like growth factor 1 (IGF-1), which increases mitotic activity in tumor cells [53, 54]. Adiponectin, also known as adipocyte-associated protein, promotes glucose and fatty acid metabolism, and improves insulin sensitivity and resistance. Adiponectin is reduced in patients with obesity, diabetes, and coronary heart disease, and a high adiponectin level is associated with lower mortality in BC patients with lower level [45]. Moreover, adiponectin was able to exert an antitumor effect by inhibiting aromatase in estrogen receptor-positive BC patients. The effect of low serum adiponectin on tumor angiogenesis is attenuated, which in turn promotes BC. In obese postmenopausal BC patients, adipose tissue is the main source of estrogen production. Estradiol is converted from androgen by aromatisation of the cytochrome P450enzyme system present in adipose tissue. Adipocytes secrete IL-6 and TNF-α, which induce aromatization together with prostaglandins. Thus, obesity can increase the production of cytokines and thereby stimulate aromatization to increase estradiol. Estradiol also reduces adiponectin production, thereby attenuating the antitumor effect of adiponectin. Sex hormone-binding globulins (SHBG) are glycoproteins produced by the liver that bind to and transport most of the biologically active androgens and estrogens in the circulation, attenuating the effects of these hormones.
Global concern
According to global survey of obesity in 195 countries, done in 2015, 604 million adults and 108 million children were obese. Since 1980, prevalence of obesity doubled in 73 countries and increased in most other countries. Of even greater concern was that the rate of increase was even higher in childhood obesity.
According to this survey, obesity is no longer a disease of affluence. The highest increase in prevalence of obesity in young men (25–29 years) occurred in countries with low socio-economic index (SDI). In the last three decades, the prevalence went from 1.1% in 1980 to 3.85 in 2015. Between 1990 and 2015, global rate of death related to high BMI increased by 28.3%. Obesity also contributed to 120 million disability-adjusted life-years.
Diet-related factors are thought to account for around 30 per cent of all cancers. Regular consumption polyphenol-rich foods are considered highly beneficial in preventing metabolic syndrome and a safeguard against breast cancer. Cocoa is an excellent source of polyphenols.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOIA CLINIC
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