Blood hormone tests can predict a woman’s risk for developing postmenopausal breast cancer for up to 20 years, according to a study led by Xuehong Zhang, MD, Channing Division of Network Medicine, Brigham and Women’s Hospital (BWH) Department of Medicine.
Using data from the Nurses’ Health Study, Zhang , Susan Hankinson, ScD, Channing Division of Network Medicine, BWH Department of Medicine and colleagues analysed 796 patients with postmenopausal breast cancer who had not received hormone therapy.
They conducted blood hormone tests at two time points: between 1989 and 1990 and between 2000 and 2002. Researchers matched each patient with two controls who were not diagnosed with breast cancer.
‘We found that a single hormone level was associated with breast cancer risk for at least 16 to 20 years among postmenopausal women not using postmenopausal hormones,’ said Zhang. ‘We, and others, are now evaluating if the addition of hormone levels to current risk prediction models can substantially improve our ability to identify high-risk women who would benefit from enhanced screening or chemoprevention-if so, the current data suggest that hormone levels would not need to be measured in the clinic more than once every 10, or possibly 20, years.’
Women with hormone levels in the highest 25 percent for estradiol, testosterone and DHEAS had a 50 percent to 107 percent greater chance for developing breast cancer compared with women in the lowest 25 percent. Relative risks for developing breast cancer were similar at one to 10 years vs. 11 to 20 years (also 16 to 20 years) after blood collection.
Researchers also investigated whether these higher levels were more closely linked to hormone-receptor positive breast cancers and if they predicted risk regardless of tumour aggressiveness.
In the first case, they found that elevated levels of estradiol increase a woman’s risk for hormone receptor-positive breast cancer, specifically oestrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) tumours.
In general, increased hormone levels, except for DHEAS, tracked closely with increased risk for receptor-positive breast cancer. Data on receptor-negative cancers were inconclusive and need additional, large studies.
Significantly, elevated hormone levels were also associated with aggressive breast cancer, which the study defined as recurrent or fatal cancer.
‘The relationship was comparable or possibly stronger for recurrent and fatal breast cancer than it was for overall breast cancer risk although these results were based on relative small numbers of participants,’ said Zhang.
Researchers also confirmed the protective effect of sex hormone-binding globulin (SHBG), which seems to negate the cancer-causing effects of certain hormones. Women in the highest 25 percent of SHBG levels had a 30 percent lower risk for breast cancer compared with women in the lowest 25 percent for SHBG levels.
Zhang noted that the study had low case numbers for several cancer subgroups, including HER2, triple-negative and basal-like breast cancers. More research is necessary to determine the relationship between elevated hormone levels and these important breast cancer groups. Brigham and Women’s Hospital

High blood cholesterol, a serious hereditary disease, is far more common than previously recognised and not treated sufficiently. This is shown in new research from the University of Copenhagen and Herlev Hospital.
A group of scientists from the University of Copenhagen has recently shown that far more Danes than expected suffer from high blood cholesterol. The study also shows that the serious hereditary disease is not treated effectively.
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Dr Børge Nordestgaard, clinical professor at the Faculty of Health and Medical Sciences, University of Copenhagen, and senior physician at Herlev Hospital is surprised at the findings.

‘We have now investigated 69,000 Danes to see how many have hereditary high blood cholesterol and have undergone sufficient treatment for the disease. We can see that out of 137 people in Denmark 1 has hereditary high blood cholesterol. That corresponds to 40,000 people with the disease in the Danish population of 5.5 million,’ states Børge Nordestgaard.
The study also shows that very few families and individuals with this serious disease have been identified and treated effectively with statins, a type of drug for treating high cholesterol. In Holland, by comparison, early detection of patients and their families has almost eliminated the increased risk of coronary disease, because effective treatment to reduce cholesterol levels was implemented quickly.
‘Never before anywhere in the world has the ordinary population been studied to see how many people and families with hereditary high blood cholesterol there actually are. It was previously assumed that only 1 out of every 500 people had it, so it was quite a surprise for us suddenly to find 3 ½ times as many people with this serious disease. At the same time, it was also startling to discover that a disease that can easily be prevented by treatment to reduce blood cholesterol has not been treated sufficiently,’ says Dr. Marianne Benn, senior physician, also from the University of Copenhagen.
Of those Danes shown to have hereditary high blood cholesterol, one-third already had coronary disease, and only half were being treated with statins. People with hereditary high blood cholesterol not undergoing treatment with statins have a 1,200 per cent higher risk of developing coronary disease. Even more surprising: people with hereditary high blood cholesterol who are being treated with statins still have a 900 per cent higher risk of incurring coronary disease. In total, the study documents massive underdiagnosis and undertreatment of these high-risk individuals and their families in Denmark.
Researchers used the internationally recognised Dutch criteria for hereditary high blood cholesterol based on very high blood cholesterol level and early-onset coronary disease in the test person and his/her family, and on the finding of mutations that directly lead to hereditary high blood cholesterol. The increased risks appear even when figures are adjusted for several other factors that also contribute to coronary disease. Researchers use this method to eliminate biased results.
These new figures mean that there are about 50 million people worldwide with hereditary high blood cholesterol. Today most of these people are undiagnosed, untreated and therefore at serious risk of dying early from coronary disease. According to the World Health Organization (WHO), coronary disease is the most common cause of death in adults worldwide. WHO estimates that at least 17 million people die from coronary disease annually. A considerable number of these deaths are due to hereditary high blood cholesterol.
‘We have known for decades about high blood cholesterol and how to prevent it. Nonetheless the disease is massively underdiagnosed and undertreated. This means that many people unnecessarily develop early-onset coronary disease and die far earlier than normal,’ says Børge Nordestgaard. University of Copenhagen

Measuring blood levels of high-sensitive C-reactive protein, an important marker of inflammation, in apparently cancer-free men could potentially help identify those at increased risk for death from cancer, in particular lung cancer.
‘Inflammation has been linked to the initiation and progression of several types of cancer, as well as to the progression of atherosclerosis and cardiovascular disease,’ said Minseon Park, M.D., Ph.D., M.P.H., assistant professor in the Department of Family Medicine at the Center for Health Promotion at Seoul National University Hospital in South Korea. ‘We wanted to determine whether there was a relationship between a well-established marker of inflammation, high-sensitive C-reactive protein (hs-CRP), and death from all causes, death from cancer or death from a site-specific cancer in Koreans.’
Park and colleagues retrospectively analysed data from 33,556 individuals who had completed medical check-ups, answered questions on cancer-related behavioural factors (like smoking status and exercise habits) and had been screened for blood hs-CRP at the health-screening centre at Seoul National University Hospital between May 1995 and December 2006. During an average follow-up of 9.4 years, 1,054 deaths from all causes and 506 deaths from cancer were recorded.
When the researchers adjusted for several variables, including age, diabetes, smoking status and exercise habits, men with the highest level of hs-CRP in their blood (3 mg per liter or more) were 38 percent more likely to have died from any cause compared with men with the lowest hs-CRP level (1 mg per liter or less). They were also 61 percent more likely to have died from cancer.
For women, after adjusting for a number of variables, no statistically significant association was observed for hs-CRP level and death from any cause or death from cancer.
Through analysis of associations between hs-CRP levels and site-specific cancers, the researchers found that a significant relationship existed only for lung cancer. After adjusting for multiple variables, individuals with the highest hs-CRP level were more than twice as likely to die from lung cancer compared with those with the lowest hs-CRP level.
The association between hs-CRP levels and all-cause mortality and cancer mortality was stronger in lean individuals compared with those who were overweight.
‘This was surprising,’ said Park. ‘Because obesity is a major risk factor for chronic diseases like cancer, physicians and the mass media often recommend eating less and exercising more. While an important public health message, some people are too concerned with these recommendations and they eat fewer calories than their body actually needs. It is important that we eat enough to meet the metabolic demands of our body to make sure our organs function adequately for a healthy life.’ EurekAlert

If you look old, your heart may feel old, according to research presented at the American Heart Association’s Scientific Sessions 2012.

In a new study, those who had three to four ageing signs — receding hairline at the temples, baldness at the head’s crown, earlobe crease, or yellow fatty deposits around the eyelid (xanthelasmata) — had a 57 percent increased risk for heart attack and a 39 percent increased risk for heart disease .

‘The visible signs of ageing reflect physiologic or biological age, not chronological age, and are independent of chronological age,’ said Anne Tybjaerg-Hansen, M.D., the study’s senior author and professor of clinical biochemistry at the University of Copenhagen in Denmark.

Researchers analysed 10,885 participants 40 years and older (45 percent women) in the Copenhagen Heart Study. Of these, 7,537 had frontoparietal baldness (receding hairline at the temples), 3,938 had crown top baldness, 3,405 had earlobe crease, and 678 had fatty deposits around the eye.

In 35 years of follow-up, 3,401 participants developed heart disease and 1,708 had a heart attack.

Individually and combined, these signs predicted heart attack and heart disease independent of traditional risk factors. Fatty deposits around the eye were the strongest individual predictor of both heart attack and heart disease.

Heart attack and heart disease risk increased with each additional sign of ageing in all age groups and among men and women. The highest risk was for those in their 70s and those with multiple signs of ageing.

In the study, nurses and laboratory technicians noted the quantity of gray hair, prominence of wrinkles, the type and extent of baldness, the presence of earlobe crease and eyelid deposits.

‘Checking these visible ageing signs should be a routine part of every doctor’s physical examination,’ Tybjaerg-Hansen said. American Heart Association

International researchers, including a team at McGill University, have discovered a new cause for thyroid hormone deficiency, or hypothyroidism. This common endocrine disorder is typically caused by problems of the thyroid gland, and more rarely, by defects in the brain or the pituitary gland (hypophysis). However, a new cause of the disease has been discovered from an unsuspected source. The scientists, led by McGill Professor Daniel Bernard, Department of Pharmacology and Therapeutics in the Faculty of Medicine, identified a new hereditary form of hypothyroidism that is more prevalent in males than in females. This sex bias shone a light on where to look for the underlying cause.
‘Our collaborators in the Netherlands had been following a family in which two cousins had an unusual syndrome of hypothyroidisim and enlarged testicles,’ said Prof. Bernard. ‘Using state-of-the-art DNA sequencing technologies, we identified a mutation in a gene called immunoglobulin superfamily, member 1 (IGSF1), in both boys and their maternal grandfather. As one of few labs in the world studying this gene, we initiated a collaboration to determine whether the observed mutation might cause the disorder. At the time, the IGSF1 gene was known to be active in the pituitary gland, but its function was a mystery’.
‘Shortly after, we were contacted independently by a second group of researchers, studying a second family, in which two young brothers suffered from hypothyroidism and also harboured a mutation in the IGSF1 gene, though it was a different mutation than that observed in the Dutch family,’ said Prof. Bernard, ‘The fact that there were two unrelated families with the same male-biased clinical syndrome and mutations in the same gene strongly suggested that the mutations played a causal role in hypothyroidism’.

The groups reached out to researchers in the Netherlands, the UK, Italy and Australia who were following similar families and found that affected males all had mutations in their IGSF1 gene. Overall, the team identified 11 families with 10 different mutations in IGSF1.

‘We went on to show that mutations in IGSF1 block the protein it encodes from moving to the cell surface, where it normally functions’, explained Beata Bak, McGill Ph.D. student and the paper’s co-first author. ‘We also observed that the pituitary glands of mice lacking IGSF1 had reduced levels of the receptor for a brain-derived hormone known as thyrotropin-releasing hormone (TRH). If we think of TRH as a key, then its receptor is the lock into which the key fits to produce its effects. Our results suggest that in the absence of IGSF1, the pituitary gland becomes less sensitive to the brain’s instructions to secrete thyroid-stimulating hormone (TSH). As a result, the thyroid gland receives a reduced impetus to produce thyroid hormones’.

The group’s findings are significant as IGSF1 mutations cause a variable, though principally mild, form of hypothyroidism that would likely escape detection by most perinatal thyroid function screening methodologies. In addition, since the IGSF1 gene is highly polymorphic, there may be many individuals (boys and men, in particular) in the general population with presently undetected, but clinically significant hypothyroidism.

Symptoms of the disease include fatigue, weight gain, cold sensitivity, and muscle weakness. If left untreated, hypothyroidism increases the risk of developing heart disease. In infants, hypothyroidism can cause neurodevelopmental delay and, in extreme circumstances, cretinism.

‘A simple test could identify carriers of IGSF1 gene mutations or variants who might benefit from thyroid hormone replacement therapy. Our results highlight a fundamental role for this protein in how the brain and pituitary gland control thyroid function and therefore the whole body metabolism. We hope our work will inspire new research on IGSF1’s function in the pituitary gland under various physiological and pathophysiological conditions’, said Prof. Bernard. McGill University