Posts Tagged ‘cancer’

Why Everyone Seems to Have Cancer

January 9th, 2014

That was the attention-grabbing headline of George Johnson’s article in the New York Times January 5, 2014. The article notes the decline in deaths from heart disease (down 68%), cancer (down 10%) and stroke (down 79%). With the advances in treatments and prevention efforts, deaths from heart disease and stroke are likely to continue, at least in the developed world. However, Johnson notes, “For the oldest among us, the two killers are fighting to a draw. But there are reasons to believe that cancer will remain the most resistant. It is not so much a disease as a phenomenon, the result of a basic evolutionary compromise. As a body lives and grows, its cells are constantly dividing, copying their DNA – this vast genetic library – and bequeathing it to the daughter cells. They in turn pass it to their own progeny: copies of copies of copies. Along the way, errors inevitably occur. Some are caused by carcinogens but most are random misprints. Over the eons, cells have developed complex mechanisms that identify and correct many of the glitches. But the process is not perfect, nor can it ever be. Mutations are the engine of evolution. Without them we never would have evolved. The trade-off is that every so often a certain combination will give an individual cell too much power. It begins to evolve independently of the rest of the body. Like a new species thriving in an ecosystem, it grows into a cancerous tumor. For that there can be no easy fix. These microscopic rebellions have been happening for at least half a billion years since the advent of complex multicellular life- collectives of cells that must work together, holding back, as best each can, the natural tendency to proliferate. Those that do not – the cancer cells – are doing, in a Darwinian sense, what they are supposed to do: mutating, evolving and increasing in fitness compared with their neighbors, the better behaved cells of the body.”

Johnson goes on to aver that more progress in preventing cancer deaths can be made “by reducing the incidence of obesity, a metabolic imbalance that, along with diabetes, gives cancer an edge.”

Two brief observations. First, for many years policy-makers’ attention to obesity has been based on its impact on cardiovascular disease. With improvements in treatments for other cardiovascular risks, such as hypertension or high cholesterol, we are seeing a reduction in cardiovascular disease, already affecting clinical trials, such as Look Ahead and SCOUT. What happens when, as Johnson predicts, heart disease is not the major killer but cancer is? And this leads to the second point. The relationship of obesity to various cancers is mixed, a sign of research-neglect. Much more work needs to be done to understand why obesity is associated with some cancers but not others, what is the effect of weight loss on cancer progression and recovery, etc. The Institute of Medicine report is an excellent starting place to begin to focus on the obesity-cancer connection.

 

 

Cancer Patients with Obesity Undertreated

September 24th, 2013

The Washington Post carries an article today on physicians under-treating cancer patients with obesity by giving lower doses of chemotherapy than appropriate for their weight. A recent paper in Nature by Lyman and  Sparreboom highlighted the problem. The American Society of Clinical Oncology has issued new guidelines urging full, weight-based doses for persons with obesity. This problem is not unique to chemotherapy by any means. An article by 10 FDA scientists in 2011 found “specific dosing recommendations for these (obese) patients are often absent in drug product labels.”

 

Obesity drives up esophageal cancer rates in Canada

October 14th, 2012

MC Otterstatter  and colleagues have reported an increase in esophageal cancer in Canada. While rare, the incidence of esophageal adenocarcinoma has doubled in the past 20 years, probably reflecting the increasing prevalence of obesity and gastroesophageal reflux disease. PubMed: Esophageal cancer in Canada: Trends

 

 

Obesity and Cancer

May 15th, 2012

I testified last week at the FDA AdCom on lorcaserin. I prepared my testimony to talk about cancer in humans, rather than cancer in rats, which I knew would be the topic of the meeting. I didn’t deliver all of the following testimony. I only had about 4 minutes so I go through about half.

M. Downey Prepared statement before Endocrinologic and Metabolic Advisory Committee on lorcaserin, May 10, 2010.

Mr. Chairman, thank you for this opportunity to appear before the Advisory Committee. I have no financial relationship with the sponsor and no one paid for my participation at this hearing.

This morning we learned a lot about tumors in rats. Thank you. I learned a lot. Over several years, the committee has discussed the health effects of obesity but I do not recall many discussions about the effects of obesity on human cancer. I have three quick points:

  • Obesity/low physical activity is associated with increased risk of cancer in both men and women

  • Mechanisms of action in different cancers is unknown

  • Weight management appears useful for cancer survivors

Mortality

One study, using NCI Surveillance, Epidemiology, and End Results (SEER) data, estimated that in 2007 in the United States, about 34,000 new cases of cancer in men (4 percent) and 50,500 in women (7 percent) were due to obesity. Recent studies indicate that obesity and being overweight may increase the risk of death from many cancers, accounting for up to 14 percent of cancer deaths in men and 20 percent of cancer deaths in women. NCI:Fact Sheet:Obesity

Epidemiology

Not only is obesity increasing, the normal weight population is totally collapsing. This is an unique change in human physiology.

This is the graph of changes in the US from 1971 to 2008.

However, new projections show that in two decades, the overweight/obese population will increase by 33% and the severe/morbidly obese population will increase by a staggering 138%, according to a new publication by Finkelstein and colleagues at RTI and CDC. AJPM:Finkelstein:Projections_2030

According to the Annual Report to the Nation on the Status of Cancer:

  • Considerable evidence suggests that excess weight may be associated with increased risk of other cancers, including gallbladder, liver, thyroid, and hematopoietic cancers.

  • Lack of physical activity is associated with increased risk of colon, endometrial and postmenopausal and maybe premenopausal breast cancer.

    Excess weight is associated with poorer survival among patients with breast cancer and colorectal cancer.” Eheman C, et al Annual Report to the Nation on the Status of Cancer, 1975-2008, Cancer 2012 May 1;118(9):2338-66

The connection between obesity and cancer have been attributed to:

  • Hormones

  • Growth Factors

  • Inflammation

However, no definitive path of causality has been established.

A study by Ma and colleagues has found starkly increased death rates due to cancer, as well as cardiovascular disease, in a large cohort of 112,000  Americans aged 18-39, followed for 16 years.  Ma J, et al,

But obesity does not appear to have a blanket effect on all types of cancers, nor to affect cancer risk the same in men and women. One study found that obesity increases the risk of dying from all cancers by about 52% in men, but nearly doubled the risk of dying from any type of cancer in women.” PubMed:Calle_2003

In 2011, the Institute of Medicine National Cancer Policy Forum held a workshop on the impact of obesity on cancer survivorship, the general trend of the dialogue was that:

  • It is still an open question on recommending and implementing weight loss among cancer survivors

  • But sufficient evidence of general benefit of lower weight on health and increased risk of recurrence with obesity

  • Practical problems of cancers survivors attempting to lose weight.

Current research:

  • Imayama et al examined the effects of diet and exercise on inflammatory biomarkers in 439 postmenopausal women. The women were randomized to 1 year of caloric restriction diet, aerobic exercise or combined diet and exercise. Women in the diet and diet + exercise group with a 5% or more weight loss reduced inflammatory biomarkers compared with controls. The diet only and diet plus exercise groups showed reductions. Inflammation has been hypothesized to be a mechanism for cancer in obese patients. Cancer Research : Effect of Caloric Restriction

    • Last year, the same research team found that a combined diet and exercise intervention had positive effects on health related quality of life (HRQOL) in overweigh/obese postmenopausal women. Weight loss predicted improvements in physical functioning, vitality and mental health. Improved HRQOL led to positive changes in depression, stress and social support. PubMed: Dietary weight loss and exercise effect on HRQOL

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. PubMed: Survivors of Uterine Cancer, SUCCEED Trial

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. PubMed: Survivors of Uterine Cancer, SUCCEED Trial

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. Hauner D, et al, The effect of overweight and nutrition on prognosis in breast cancer. Dtsch Arztebl Intl 2011 Nov. 108(47):795-801/ PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. Von Gruenigen V et al, Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEES): A randomized controlled trial, Gyneco Oncol 2012 Mar 28 PubMed: Survivors of Uterine Cancer, SUCCEED Trial

 

Increasing Rates of Some Cancers Associated with Obesity

January 28th, 2012

Increasing rates of some cancers may be associated with obesity. Cancers with increasing incidence trends in… [CA Cancer J Clin. 2012] – PubMed – NCBI

Staggering New Cost Projections for Obesity

November 22nd, 2011

Simulation model predicts increased health care costs and utilization in rising obese populations in the United States and the United Kingdom, predicting 65 million more obese in the US and 11 million more in the UK, meaning 6 to 8.5 million cases of diabetes, 5.7 to 7.3 million cases of heart disease, 492,000 to 669,000 additional cases of cancer in the US and UK combined. The combined health care costs increases are $48-66 billion per year in the US and by £1·9-2  billion  per year in the United Kingdom. Health and economic burden of the projected obesity t… [Lancet. 2011] – PubMed – NCBI

Cancer and Obesity Explored

November 3rd, 2011

The Institute of Medicine’s National Cancer Policy Forum this week convened a two-day workshop, “The Role of Obesity in Cancer Survival and Recurrance.” So this is a good opportunity to re-visit the relationship between these two deadly diseases. Susan Gapstur of the American Cancer Society noted the growing list of cancers associated with obesity. For men, these include cancers of the colon, esophagus, kidney, colorectum, pancreas, gallbladder and liver. Women are affected by the same cancers as well as of the endometrium and postmenopausal breast cancer. Evidence is accumulating for an association with non-Hodgkin’s lymphoma, ovarian cancer in women and aggressive prostate in men. Obesity, she pointed out, is not the second (to tobacco) leading risk factor of cancer. Ominously, she pointed out we do not know what the health effects will be for the children now obesity who will obese for a lifetime.

Pamela J. Goodwin of the University of Toronto explored potential mechanisms in the progression to cancer including inflammation, adipokines, hyperinsulinemia, diabetes/diabetes drugs and sex steroids. She pointed to studies showing reductions in cancer risk with intentional weight loss of 20 pounds or more. Intentional weight loss and in… [Int J Obes Relat Metab Disord. 2003] – PubMed – NCBI and reduction in the relative risks of death and of cancer following bariatric surgery. Metabolic surgery and cancer: protective effects of b… [Cancer. 2011] – PubMed – NCBI.  Specifically, she showed the positive effect of intentional weight loss on breast cancer risk   Does intentional weight loss reduce canc… [Diabetes Obes Metab. 2011] – PubMed – NCBI and the impact of physical activity on improvements in insulin in breast cancer survivors Impact of a mixed strength and endurance exerci… [J Clin Oncol. 2008] – PubMed – NCBI.

Bruce Wolfe of the Oregon and Science University and a bariatric surgeon reminded the participants that the Swedish Obesity Study found the reduction in mortality after bariatric surgery was greater for cancer than for cardiovascular events Effects of bariatric surgery on mortality in Sw… [N Engl J Med. 2007] – PubMed – NCBI. In a Utah study, bariatric surgery reduced deaths from cancer by 60% compared to a 48% reduction in cardiovascular events. Long-term mortality after gastric bypass surgery. [N Engl J Med. 2007] – PubMed – NCBI

Rachel Ballard-Barbash of the National Cancer Institute, who has been a leader in exploring the obesity-cancer connection for many years, moved the discussion to look at the co-morbid conditions of obesity and their relationship to cancer mortality, including renal disease, congestive heart failure, cerebrovascular disease, citing A refined comorbidity measurement algorithm fo… [Ann Epidemiol. 2007] – PubMed – NCBI

Patricia Ganz of the UCLA Schools of Medicine picked up the point and explained that about half of all deaths of breast cancer survivors are due to causes other than breast cancer. She recommended prevention of weight gain and/or weight loss in those breast cancer survivors who are obese. 

Thomas Wadden described the non-surgical approaches to weight loss used in the Diabetes Prevention Program and the LOOK Ahead study and the contribution of intensive behavioral counseling to reduction in comorbid conditions associated with obesity

Some of the workshop’s presentations are on-line at Workshop on the Role of Obesity in Cancer Survival and Recurrence – Institute of Medicine. Watch that site for future information on a publication from the workshop.

IOM Announces Workshop on Obesity and Cancer Survival

September 5th, 2011

The Institute of Medicine will be holding a workshop on the effect of obesity on cancer survival in Washington, DC on October 31- November 1, 2011. Information is available at Workshop on the Role of Obesity in Cancer Survival and Recurrence – Institute of Medicine