Smoking and obesity are two of the most important behavioural risk factors for premature death in the western world, but it is not known whether smoking and weight have combined effects on the risk of death.

The authors, led by Dr Martin Neovius at Karolinska Institute in Sweden, analysed the cause of death of over 45,000 men who underwent mandatory military conscription tests in Sweden. The participants all had their body mass index (BMI) measured and reported their smoking status at the age of 18 and were followed up for an average of 38 years. In total, the authors assessed 1.7 million person-years of follow-up in relation to the health and mortality of all the participants.

During the follow-up period 2,897 subjects died, the incidence of death was lowest for people with normal weight and highest in obese subjects.

Compared to normal weight adolescents, being overweight at the age of 18 increased the risk of premature death by just over a third, while being obese more than doubled the risk.

Being underweight carried no increased risk, irrespective of smoking status. However, being seriously underweight (a body mass index of less than 17) carried the same risk of premature death as being overweight.

Early death was also linked to the number of cigarettes participants smoked per day. This risk gradually increased the more participants smoked, with heavy smokers at more than double the risk of premature death compared to non-smokers.

But, interestingly, when the effects of weight and smoking were combined, the researchers found no significant change in the results. The combination of obesity and heavy smoking was associated with a large excess risk of early death (almost five times greater than normal weight non-smokers). However, there was no statistically significant interaction between these two factors.

This means that being overweight or obese at the age of 18 increases the risk of premature death, regardless of smoking status, they explain.

The authors note that since the baseline measurements for this study were carried out, the number of adolescent men who are overweight in Sweden has tripled and those who are obese has increased five-fold. However, the number of men who smoke and are underweight in Sweden has halved. Internationally, there have been marked increases in overweight and obesity, but also in adolescent smoking in some countries.

Dr Neovius and his colleagues therefore conclude that “overweight, obesity and smoking among adolescents remain important targets for intensified public health initiatives.”

“Research: Combined effects of overweight and smoking in late adolescence on subsequent mortality: nationwide cohort study.”

Cancer of the liver, also known as hepatocellular carcinoma, is the fifth most common type of cancer in the world. It is increasing in incidence, largely due to the spread of hepatitis C. Its growing prevalence may also be related to the rise of obesity and type-2 diabetes, which are associated with non-alcoholic fatty liver disease (NAFLD). However, liver cancers associated with NAFLD have been poorly described.

Researchers, led by Valerie Paradis of Beaujon hospital in Paris, decided to analyze a series of liver cancers which arose in patients whose only risk factor for chronic liver disease was metabolic syndrome. They compared their findings to the characteristics of hepatocellular carcinomas that developed in the setting of other chronic liver diseases.

Their retrospective analysis included 128 patients in their hospital who had undergone surgery to remove a liver tumor between 1995 and 2007. Of these, 81 patients had an overt cause of chronic liver disease (CLD), like hepatitis B or hepatitis C. Thirty-one patients had features of the metabolic syndrome (MS) as their only risk factor. And sixteen patients had no identifiable risk factors.

“Most hepatocellular carcinoma associated with features of metabolic syndrome as the only risk factor for chronic liver disease develop in non-fibrotic liver,” the authors report. They found that just over 35 percent of liver tumors in these patients occurred in bridging fibrosis or cirrhosis, compared to 75 percent in the patients with chronic liver disease.

“Our results suggest that well-recognized multistep progression, i.e. fibrosis-cirrhosis-HCC, may not be the main carcinogenic pathway in the context of metabolic syndrome,” they write. They suggest that the metabolic syndrome itself could have a direct cancer-causing effect, perhaps through the effects of insulin, lipid peroxidation or free radical oxidative stress.

They noted that most tumors arising in the context of the metabolic syndrome were well differentiated – nearly 65 percent compared to 28 percent in the patients with chronic liver disease. These tumors were more similar to those in patients with tumors from unknown causes, which also had better differentiation and a low prevalence of significant fibrosis.

Interestingly, the researchers found that among the patients with metabolic syndrome, five cases of liver cancer were associated with liver cell adenoma (a benign liver tumor).

“Our results suggest that a significant percentage of hepatocellular carcinoma that developed in the context of metabolic syndrome without significant fibrosis arose from malignant transformation of liver cell adenoma,” they report.

Also Included In: Cancer / Oncology; Obesity / Weight Loss / Fitness; Diabetes

The researchers used an imaging technique to document how increasing fat content causes cancer cells to undergo changes essential to metastasis. Then they used another technique to count the number of cancer cells in the bloodstream of mice fed a high-fat diet compared to animals fed a lean diet.

The findings suggest that the combined tools represent a possible new diagnostic technique to determine whether a patient’s cancer is spreading, said Ji-Xin Cheng, an assistant professor in Purdue’s Weldon School of Biomedical Engineering and Department of Chemistry.

“It is generally accepted that diet and obesity are accountable for 30 percent of preventable causes of cancer, but nobody really knows why,” Cheng said. “These findings demonstrate that an increase in lipids leads directly to a rise in cancer metastasis.”

Researchers have theorized that tumor cells need more lipids than ordinary tissues to provide energy and material for tumor growth and metastasis.

“Before this work, however, most of the evidence was anecdotal, but here we present a mechanistic study,” said Thuc T. Le, a National Institutes of Health postdoctoral fellow at Purdue who is working with Cheng.

Findings were detailed in a paper published on Jan. 30 in the journal BMC Cancer. The paper was written by Le; Terry B. Huff, a graduate research assistant in Purdue’s Department of Chemistry; and Cheng. The research is supported by the Purdue Cancer Center.

The researchers implanted a cancerous lung tumor under the skin in each of the mice studied, and the animals were separated into two groups: one fed a high-fat diet and the other a lean diet.

The researchers then used an imaging method called coherent anti-Stokes Raman scattering, or CARS, to document how increasing lipids from fat intake induces changes to cancer cell membranes. Those changes, including processes called membrane phase separation and membrane rounding, enhance cancer metastasis.

“If the cancer cells don’t have excess lipids they stick together and form very tight junctions in tumors, but increasing lipids causes them to take on a rounded shape and separate from each other,” Le said.

The change in shape is critical to the ability of cancer cells to separate and spread throughout the body via the bloodstream.

The researchers then used another technique, called intravital flow cytometry, to count the number of cancer cells in the bloodstream of the mice. The technique works by shining a laser though the skin and into blood vessels, where the dyed cancer cells are visible.

Results showed the increase in lipids had no impact on the original tumors implanted in the mice. However, the rate of metastasis rose a dramatic 300 percent in the mice fed a high-fat diet.

The researchers later also examined the animals’ lungs and counted the number of cancer cells that had migrated to the lungs as a result of metastasis. Those findings supported the other results showing increased metastasis in animals fed a high-fat diet.

The researches used the imaging and cell-counting tools to document that linoleic acid, which is predominant in polyunsaturated fats, caused increasing membrane phase separation, whereas oleic acid, found in monounsaturated fats, did not. Increased membrane phase separation could improve the opportunity of circulating tumor cells to adhere to blood vessel walls and escape to organs far from the original tumor site. The new findings support earlier evidence from other research that consuming high amounts of polyunsaturated fat may increase the risk of cancer spreading.

The findings suggest that combining CARS and intravital flow cytometry represents a possible new diagnostic tool to screen patients for cancer. The tool can be used to count lipid-rich tumor cells circulating in a patient’s blood by shining a laser through the skin and into blood vessels. Because lipids can be detected without the need for dyes, the technique might be developed into a convenient method to diagnose whether a patient’s cancer is spreading aggressively, Cheng said.

“These findings open the possibility of an entirely new, relatively simple method for diagnosing whether cancer is metastasizing,” he said.

Future work will focus on not only how obesity increases metastasis but also how it might play a direct role in initiating the development of cancers.

The research has been funded by the National Institutes of Health.

Writer: Emil Venere

ABSTRACT

Coherent Anti-Stokes Raman Scattering Imaging of Lipids in Cancer Metastasis

Thuc T Le1, Terry B Huff2 and Ji-Xin Cheng*1,2,3

1Weldon School of Biomedical Engineering, Purdue University; 2Department of Chemistry, Purdue University; 3Purdue Cancer Center

Background: Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Methods: Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high-fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. Results: CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Conclusion: Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.

In the UK, 45 per cent of people agreed with the statement “I like the taste of fast food too much to give it up”, compared to 44 per cent in the US.

One in five named “unhealthy food choices” as the cause of obesity, while the same percentage chose “unhealthy food habits like eating at irregular hours”.

Overall, lack of exercise was named the main cause of obesity by 18 per cent of people while 13 per cent blamed “no self discipline” and 11 per cent put it down to “genetics”.

In the UK, unhealthy food choices, lack of exercise and no self-discipline were the highest ranked reasons.

Douglas Smallwood, Chief Executive of Diabetes UK, said: “This survey is a sad indictment of current eating habits in the UK.

“Obesity is one of the leading causes of Type 2 diabetes, a serious condition which can lead to heart disease, kidney failure and blindness. Soaring obesity levels mean that 100,000 new cases are diagnosed every year.

“Diabetes UK urges people to eat a healthy, balanced diet. This does not mean that people have to completely give up fast food but because fast food is high in fat, salt and sugar, it should only be eaten occasionally.”

The study by BBC World and market research firm Synovate aimed to uncover global attitudes to food and obesity across the UK, France, Czech Republic, Romania, USA, Canada, Brazil, United Arab Emirates, Saudi Arabia, Hong Kong, Singapore, Malaysia and Australia.

http://www.diabetes.org.uk

Colleen Greene, wellness coordinator with MFit, the University of Michigan Health System’s health promotion division, says that in order for a workout plan to succeed a person must realize that pounds won’t come off within the first clutch of a dumbbell. Instead, exercise must become part of a regular routine rather than be thought of as a short-term solution.

“The number one New Year resolution people have is to lose weight, and it is really not that difficult. But many expect it to be done overnight, and they lose their motivation when that doesn’t happen,” says Greene. “You didn’t gain weight overnight, so you’re not going to lose it overnight either.”

One main way people jump into a fitness routine is by joining a gym. But often the motivation disappears only weeks after a new membership. Greene offers several tips on how to start and stick with a new workout plan.

1. Join a fitness center that is convenient to your lifestyle. “It’s great if you see that a fitness center across town is all new and sparkly, but if you have to fight cross-town traffic to get there it’s probably not a good choice,” advises Greene. It is also important to make sure the center’s hours mesh with your schedule, if it offers child care or other programs you may need and that it has a qualified staff.

2. Ask questions. Don’t be shy about learning all that the fitness center has to offer, says Greene. Most gyms have specialists and personal trainers that can help you navigate equipment and devise the best plan for your fitness needs. You should also get the OK from your doctor as you begin a new workout routine, and ask any questions that you may have about your health.

3. Try things you’ve never done before. “If you think Pilates is something for dancers only or if you think yoga means standing on your head, most gyms will have some sort of special drop-in rate for either the first week or first few sessions of a class,” says Greene. “Go ahead and try it! You may find that you like it.”

4. Aim to meet your goals gradually. Greene notes that the most common mistake people make when they join a gym is coming in and doing everything at once. Instead, work toward your goals at a steady pace so that you can sustain your new fitness routine.

5. Schedule time to exercise into your calendar. “Sometimes people burn out because other things happen; they have this or that responsibility. Remember that you have a responsibility to yourself too,” says Greene. Incorporate exercise into your daily routine so that it becomes part of your day and not something you can easily blow off.

6. Get a support system. Find people you can count on, whether it is an exercise buddy or someone taking care of your responsibilities at home or on the job, so you have time to work out.

7. Make your exercises fun! Working out does not have to be drudgery. Many fitness centers have intramural leagues and an assortment of classes. Also add a variety of workouts to your routine to prevent boredom. “Find out what you like and switch it up every so often,” Greene suggests.

As the winter months roll along, you may begin to feel less motivated. But Greene notes that there is one thing to always remember: “Fitness is a time for you and a time to take care of yourself,” she says. “You will end up feeling good because you’ll be getting fit and feeling better.”

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Colleen Greene, wellness coordinator with MFit, the University of Michigan Health System’s health promotion division, says you don’t have to invest a lot of money in a gym membership or equipment to develop a successful and sustainable fitness regimen.

Her first piece of advice is to make a resolution to become healthier overall, instead of only focusing on dropping pounds. This will broaden your goals and encourage you to make lifestyle changes rather than temporary adjustments.

“Traditionally the number one New Year’s resolution is to lose weight, but it should not necessarily only be that. It should be improving your fitness, and losing weight may be part of that,” says Greene.

By purchasing the right equipment, adding creativity to your workouts, and keeping your motivation up, you can start an exercise program around the house that will last. Greene offers the following tips:

1. Get a fitness assessment. An assessment done by a personal trainer will help you decide what your goals should be. For example, it will show if you need flexibility work or if instead you should focus on increasing your cardiovascular capacity. This will provide a starting point for fitness planning. Also, be sure to check with your doctor to ensure that your new routine will be the best and safest one for your individual needs.

2. Purchase equipment that is right for you. Don’t get something that is just going to end up a coat hanger, Greene advises. “You want to look at what is exciting to you, what you will do and what to focus on once your assessment has been done,” she says. “Do you need the cardiovascular exercise? Buy a cardiovascular machine. Do you need some strength training? Purchase a Dyna-band or small hand weights. It depends on what sort of equipment you need and what sort of equipment you are going to use.”

3. Be creative. Do you have a can of soup? Then you’ve got yourself a dumbbell. Using the resources around you not only mixes up your routine, but it saves you some money too. You can even use your own body weight to do various resistance exercises that help to increase your strength, Greene says.

4. Embrace the outdoors. There are many winter activities that people can do outside that can be fun and safe. Snowshoeing, cross country skiing and even going outdoors to play with your children are great ways to integrate exercise into your life during the winter months.

5. Maintain a support system. Whether you need a friend to work out with or someone who will help you stay motivated, Greene emphasizes the value of getting support to help you commit to your new routine. Even if it is asking a family member to do the dishes so you can get a workout in, other people can greatly aid in making your resolution a reality.

6. Change up your routine. Not only can adding a mix to your workouts prevent injuries, it can also add some “spice” to your routine. Greene notes that the more fun you make exercise, the more likely you are to sustain it. Changing up a routine also gives you the chance to target different areas of your body. While the typical recommendation for cardiovascular activity is 20 to 30 minutes at your target heart rate five to six days a week, it is important to engage in both aerobic and weight-training activities because research has also shown that strength training should be a part of every workout as well.

7. Realize that weight loss won’t happen overnight. Greene suggests that a one- to two-pound weight loss per week is a realistic expectation, but it will take time to see significant results. Instead of only paying attention to the numbers on the scale, focus on how your clothes are feeling, how your resting heart rate is dropping and how you have more energy overall.

So turn on the TV and hop on the elliptical machine in the comforts of your own home, or throw on your snow boots and run around with the kids. The most important thing is simply making sure you take the time to do it. “Just like any meeting or any event, schedule exercise in,” says Greene. “It’s your time, and you are worth it.”

University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
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http://www.med.umich.edu

Researchers at the Albert Einstein College of Medicine of Yeshiva University, in New York, identified the FIT1 and FIT2 (Fat-Inducing Transcripts 1 and 2) genes that package fat in the form of lipid droplets.

Scientists say that storing fat in lipid droplets is important for enabling cells to use fat as an energy source, but having high amounts of these droplets leads to obesity.

“This new research could help us get closer to unravelling the genetics of obesity,” said Douglas Smallwood, Chief Executive at Diabetes UK.

“Obesity is a major cause of Type 2 diabetes, with around 300 people diagnosed with the condition every day. The discovery of genes that influence the development of obesity could help us understand why some people gain weight more than others.

“These findings could open up a wealth of new avenues to understand and treat obesity and obesity-related conditions such as Type 2 diabetes.

“Diabetes UK welcomes further research as this study is still in its very early stages.”

The research is published in the Proceedings of the National Academy of Sciences.

http://www.diabetes.org.uk

Dr Michael Korenkov, Department of Abdominal Surgery, University of Mainz, Germany, and Dr Stefan Sauerland, Institute for Research in Operative Medicine, University of Witten/Herdecke, Germany, authored the Clinical Update, and in it refer to two recent studies which showed bariatric surgery reduced mortality in morbidly obese patients by 29% and 40% respectively.

They examine the two divisions of bariatric procedure-gastric restrictive, which reduce food intake; and malabsorption, those that reduce food uptake from the digestive tract. The different types of operation available within each division are discussed in detail, with the authors commenting that the choice of surgical procedure “partly depends on the repertoire of the surgeon.” Different types of operation are more or less common depending on the world region.

Of course, the effectiveness of obesity surgery has been traditionally measured only in terms of excess weight loss-for which data clearly indicate the effectiveness of all procedures. The authors say: “Today, research emphasis is more on the effect of surgery on obesity-related comorbidities, which can affect metabolic, cardiovascular, respiratory, gastrointestinal, musculoskeletal and urological organ systems. Additionally, the psychological benefits of weight loss are being investigated. New data indicate that at least some bariatric procedures exert their beneficial metabolic effects not only by weight loss but also through a change in hormone release from the gut. This finding corresponds to clinical observations that obesity in patients with diabetes is especially amenable to bariatric surgery.”

The authors feel that as with other surgical disciplines, expertise of the surgical team is crucial in determining outcome, and call for knowledge and skills to be concentrated in bariatric surgery centres. They say: “Mortality in high-volume centres is lower than in lower-volume centres.”

They conclude: “In summary, there is good evidence to show that bariatric surgery is more effective than non-surgical approaches in the therapy of morbid obesity. However, no single operation is ideal for every morbidly obese patient, and all operations also entail some disadvantages.”

The Lancet

Today, researchers at the American Association for Cancer Research’s Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, present some of the latest research linking obesity, diabetes and metabolism to cancer risk. Their findings link weight gain and diabetes to a variety of cancers affecting both men and women, including breast, prostate and colorectal cancer

Diabetes and hyper-insulinemia as predictors of colorectal cancer risk in a prospective cohort of women. Abstract no. B93:

Women with diabetes are 1.5 times more likely to develop colorectal cancer than those who do not have the metabolic disorder, according to researchers at the University of Minnesota. The findings, they say, add to the complex body of evidence linking diet and colorectal cancer and also provide new evidence that furthers our understanding of the role of insulin in cancer promotion.

“Colorectal cancer and type II diabetes share a number of common factors, including obesity, so it is interesting to see the direct line between these two conditions,” said Andrew Flood, Ph.D., assistant professor in the Division of Epidemiology and Community Health at the University of Minnesota School of Public Health and the University of Minnesota Cancer Center “In general, the idea is that if elevated insulin levels create a biochemical environment conducive to cancer growth, it provides one mechanism by which diet and lifestyle can really influence cancer risk.”

With funding from the National Cancer Institute, Flood and his colleagues examined data from a massive screening study called the Breast Cancer Detection Demonstration Project, initiated at 29 centers throughout the United States in the 1970s. Flood’s team subsequently followed more than 45,000 study participants with no history of colorectal cancer or self-reported diabetes for eight years, (from 1987-1989 and from 1995-1998), to identify which of them subsequently developed colorectal cancer. According to their findings, women with diabetes had a greatly increased risk of developing colorectal cancer. “These results remained statistically significant even after controlling for all known and suspected confounding variables,” Flood said.

According to Flood, it is not exactly clear what aspect of diabetes is the underlying cause for this increased risk, but one hypothesis centers on the elevated concentration of insulin typically seen in people with type II diabetes. “In the early stages of the disease process, people become insulin resistant, meaning they must produce more and more insulin to regulate their blood sugar,” Flood said.

“Even after frank diabetes begins, insulin levels remain chronically elevated for extended periods before the pancreas can no longer supply the level of insulin the body demands,” Flood said. “If the elevated insulin is the problem, then pre-diabetics, who are also hyper-insulinemic, should also be at increased risk (for developing colorectal cancer).”

To test that idea, Flood and his colleagues re analyzed the data, this time including women who were likely pre diabetic at the beginning of the follow up period. The idea, Flood says, is that these women were likely hyper-insulinemic at that stage. Surprisingly, the elevated risk, while still significant, had dropped slightly in comparison with that of known diabetics, Flood says.

According to Flood, this suggests that either the pre diabetic women had not had elevated insulin long enough or intensely enough to increase risk as they observed in the diabetic women, or alternatively, something other than or in addition to hyper-insulinemia could explain the significant, increased risk for colorectal cancer they observed in people with diabetes.

Fasting C peptide levels and breast cancer death in women with breast cancer: The Health, Eating, Activity and Lifestyle (HEAL) Study. Abstract no. B99:

Women with invasive breast cancer and high blood levels of C-peptide (a marker of insulin secretion) face a risk of death nearly three times higher than women with lower blood levels of C-peptide, according to findings from the Health, Eating, Activity and Lifestyle (HEAL) Study, a long-term observational study of breast cancer patients. The effect was most notable, researchers say, among women in their 40s.

While previous research has demonstrated that insulin stimulates the growth of breast cancer cells in the laboratory, few studies have examined the link between fasting insulin or C-peptide levels and breast cancer prognosis. Women with invasive breast cancer meaning the cancer had spread throughout the breast tissue or to surrounding tissues faced the greatest risk from high C-peptide levels, the researchers say, but the association was detected in nearly all women studied, regardless of whether or not their cancer had spread.

“When looking at risk of diabetes and hypertension, breast cancer survivors really should talk to their oncologist about how to lower their insulin levels,” said Melinda L. Irwin, Ph.D., M.P.H., assistant professor at Yale University’s School of Public Health. “The simple message is that breast cancer patients should take proven steps to lower their blood insulin levels, including exercise and eating a diet rich in fruits and vegetables and low in fat.”

The HEAL Study is a National Cancer Institute initiative designed to examine the links between diet, physical activity, body fat, and breast cancer prognosis. Patients enrolled in the HEAL Study — including those participating in the study reported here were diagnosed or treated at the Fred Hutchinson Cancer Research Center, the University of New Mexico or the University of Southern California.

Between 1995 and 1998, the researchers followed 689 women enrolled in the HEAL program who were diagnosed with breast cancer, but who did not have type 2 diabetes. They monitored their health at periodic intervals beginning six months after diagnosis until September 2004 or the patient’s death. From each patient, they collected a fasting blood sample a common technique for measuring a baseline of insulin or C-peptide levels and information on prognostic, demographic, and lifestyle factors, including weight and height.

In order to determine the relationship between C-peptide levels and prognosis, Irwin and her colleagues statistically adjusted the data they collected for confounding variables such as body mass index, age, race, disease stage and therapy used in treatment. They found that, when arranged into three groups based on C-peptide levels, women in the top third of the group (highest levels) had twice the risk of death compared to women in the bottom third. When looking at just women with invasive breast cancer, the risk of death among women with high C-peptide levels was three times higher than among women with low C-peptide levels. “Our findings clearly show that C-peptide and most likely insulin, in and of itself, is a marker for breast cancer prognosis,” Irwin said.

According to Irwin, the association was also common in women in their 40s with early stage breast cancer, and less pronounced in women in their 50s or 60s. “The higher death rate among younger women suggests that these women may have had more aggressive tumors, possibly related to tumor genetics or family history,” said Irwin.

Association of C-peptide concentration with prostate cancer incidence in a prospective cohort. Abstract no. B89:

While studies have consistently shown that men with diabetes are at a decreased risk for prostate cancer, the reasons have been unclear. By evaluating prostate cancer data from a large, long-term cohort study, researchers at Johns Hopkins University have shown that those with high concentrations of C-peptide a marker of high insulin secretion that is a hallmark of diabetes had a measurable decrease in prostate cancer risk.

“Metabolic perturbations influence cancer risk, that much is becoming clear to us, and we are learning more about the fundamental issues in biology that guide prostate cancer development,” said Gabriel Lai, a doctoral student in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. “One interesting possibility is that, over time, diabetics generally have less testosterone in their bloodstream than non-diabetics, which might lower risk of prostate cancer.”

Lai and his colleagues used data from a large-scale study known as CLUE II, which had enrolled almost 23,000 adults in Washington County, Maryland in 1989. With funding from the National Cancer Institute, they examined the history of 264 men with confirmed prostate cancer and matched them with a group of 264 men without prostate cancer with a similar distribution of age and race.

For each participant, the researchers measured the amount of C-peptide in the blood they donated when they enrolled in the study. Researchers consider C-peptide to be a surrogate marker for insulin secretion because both molecules derive from the same precursor molecule, with insulin degrading faster than C-peptide. They found that patients that had elevated levels of C-peptide in their bloodstream when they started the study were about one-third less likely to develop prostate cancer later. This was true even among men without diabetes.

The researchers also report a markedly lower risk of non-metastasized prostate cancer. Men with higher C-peptide levels in their blood were half as likely to develop organ-confined prostate cancer, Lai says.

“Even though diabetes and obesity are often linked to different types of cancer, our findings illustrate the idea that the link between cancer and metabolic diseases is not the same for every variety of cancer,” Lai said. “Obviously, having high levels of insulin does not promote health but perhaps such disorders can provide insight into the mechanisms of prostate cancer to help us learn how to eventually prevent prostate cancer.”

Post diagnosis weight change, body mass index, and breast cancer survival. Abstract no. B95:

Gaining weight following a diagnosis of invasive breast cancer could increase a woman’s risk of death from the disease by more than half, according to researchers leading the Collaborative Women’s Longevity Study. In fact, the researchers associated weight gain with a measurable increase in risk of death due to all causes, not just breast cancer.

“Our findings provide additional support for the benefits of maintaining a healthy weight and exercising,” said Hazel B. Nichols, a doctoral student in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. “According to our results, there is a 14 percent increase in risk for every five kilograms — about 11 pounds — of weight gained.”

To analyze the effect of weight gain on breast cancer survival, Nichols and her colleagues contacted women who had taken part in one of three previous studies begun in 1988 at sites in Wisconsin, Massachusetts and New Hampshire. Between 1998 and 2001, Nichols’ team surveyed the women about post-diagnosis weight, weight gain, physical activity, diet and related items.

Of the original 4,021 breast cancer patients, the researchers identified 121 breast cancer-related deaths and 428 total deaths. For women classified as obese by body mass index a measure of weight and height the risk of dying from breast cancer was nearly 2.4 times that of women classified with a normal body weight. “Obesity was associated with risk of death even after accounting for age, menopausal status or smoking,” Nichols said.

Nichols’study was funded by the Susan G. Komen for the Cure Breast Cancer Foundation.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

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Researchers conducted advanced three-dimensional bone scans on 115 women ages 18 and 19 with normal (less than 32 percent) and high (greater than 32 percent) body fat. After adjusting for differences in muscle mass surrounding the bone, the researchers found that the bones of participants with high body fat were 8 to 9 percent weaker than those of normal body fat participants.

“Obesity is an epidemic in this country, and I think this study is critical because it highlights another potential negative health effect that people haven’t considered,” said study co-author Richard D. Lewis, professor of foods and nutrition at the UGA College of Family and Consumer Sciences.

Previous studies on bone health and obesity used a two-dimensional bone densitometer that is commonly used in osteoporosis screenings. Lewis explained that a notable shortcoming of the bone densitometer is that it does not take into account bone shape and geometry, which have a substantial influence on bone strength. The new study used a three-dimensional imaging technique that measures both the amount of mineral in the bone and its shape and geometry. The study found that, surprisingly, normal- and high body-fat young adult females have comparable bone strength in a direct comparison that does not account for muscle mass.

“The fact that the two groups had similar bone strength measures is remarkable in itself, because you would expect it to be higher in the heavier person,” Lewis said.

Doctoral candidate Norman Pollock, lead author of the study, explained that muscle exerts force on bones, which stimulates bone growth. Overweight people tend to have more muscle surrounding their bones than their leaner counterparts, leading most researchers to assume that being overweight is good for bone health.

“When we corrected for the amount of muscle, we found that the obese person is not making as much bone as they should be for the amount of muscle that they have,” Pollock said. “People haven’t observed that in the past because they weren’t using the three-dimensional scan.”

Lewis said the exact mechanisms by which excess fat hinders bone strength are unclear, but studies of obese rats show that they produce more fat cells in the bone marrow and fewer bone cells. Since fat and bone cells originate from the same precursor, it may be that fat cell production is favored over bone cell production in obese people.

The women the researchers studied were 18 and 19, an age at which the bones have stopped growing but before age-related degeneration begins. Lewis said future studies using three-dimensional bone imaging should follow children with normal and high levels of body fat through time to see how their skeletons grow. Other researchers have documented increased fractures in overweight children, suggesting that childhood obesity may be particularly detrimental to bone health.

“When you’re young you have the capacity to change the shape of your bones, but when you get older you don’t have that capacity.” Lewis said. “And because of that, childhood obesity could have a significant, long lasting negative impact on the skeleton.”