Mammography in Obesity: Too Little – Too Late?
I have previously blogged on the fact that women with a BMI of 35 or higher are nearly 40 percent less likely than normal weight women to have had a Pap test (for detection of cervical cancer) in the last 12 months (see Pap Gap – June 12-2008). It seems that there are also significant deficits in screening for breast cancer in obese women (J Gen Intern Med. 2009 May). In this systematic review of the literature on obesity and mammography in the United States, Nisa Maruthur and colleagues (including my friend Fred Brancati) from Johns Hopkins University, Baltimore, MD, USA, included 17 studies that met their selection criteria. Increasing BMI was associated with a significantly reduced likelihood of having received a mammography in the last 2 years (post-menopausal women with BMI>35 were almost 20% less likely to have received this exam), compared to normal-weight women. It appears that as for Pap exams for cervical cancer, obese women are also less likely to be screened for breast cancer. While the reasons for this finding are not clear, it may well be that these lower screening rates partly explain the higher breast cancer mortality seen in severely obese women. Given that the substantially increased risk of breast cancer in post-menopausal obese women, it will be important to fully understand the determinants and barriers to cancer screening in this vulnerable population. AMS Edmonton, Alberta
Why Obesity Promotes Cancers
A new report released yesterday by the World Cancer Research Fund and the American Institute for Cancer Research states that most cancers are preventable. Poor diet, lack of exercise, obesity and smoking account for the vast majority of cancers; the role of genetic factors is by far overrated. Indeed, the dramatic impact of obesity on cancer is now increasingly appreciated – one in three cancers may be caused by obesity (or as a result of lifestyle factors that promote obesity). It is therefore perhaps not surprising, that large prospective studies have shown an almost 60% reduction in deaths from cancer with bariatric surgery. But how does obesity (or poor diet) promote cancers? New insight into the mechanistic relationship between high fat intake (not uncommon in obese individuals) and cancer come from a recent study published in BMC Cancer by Thuc T Le and colleagues from, Purdue University, West Lafayette, Indiana, USA. Their study showed that feeding cancer-prone mice a high fat diet leads to increased fat accumulation in cancer cells, which in turn is incorporated onto the cancer cell membranes, thereby reducing cell-cell contact, increasing surface adhesion, and promoting tissue invasion by cancer cells. They also showed that visceral adiposity and increased plasma free-fatty-acid levels (a common finding in abdominally obese individuals) are associated with early rise in circulating tumour cells and increased lung metastasis. Thus, these studies provide insight into a mechanism directly linking increased fat intake, abdominal adiposity, and higher circulating fatty acid levels to the spread of cancer cells. Evidently, much of cancer should perhaps now be best classified as a “lifestyle disease” (a term often used to “trivialize” obesity). Prevention and treatment of obesity may prove to be the most effective “cure” for cancer after all. AMS Edmonton, Alberta Hat tip to Jacob Berkowitz for bringing the latter study to my attention.
Bypassing Breast Cancer?
The strong link between obesity and many forms of cancer is well documented. Not surprisingly, previous studies on obesity surgery have shown dramatic reductions (up to 60%) in overall cancer mortality. These data are supported by yet another study, this time from Nicolas Christou and colleagues from McGill University in Montreal. Apart from being a renowned Canadian bariatric surgeon, Christou is also the Past-President of the Canadian Association of Bariatric Physicians and Surgeons. In this study, published in in the latest issue of Surgery for Obesity and Related Diseases, Christou and colleagues conducted an observational 2-cohort study consisting of a treatment cohort of 1035 patients who had undergone bariatric surgery from 1986 to 2002 and a control group consisting of 5746 age- and gender-matched morbidly obese patients identified from an administrative database. The cohorts were followed up for a maximum of 5 years. While the patients who underwent bariatric surgery (mostly gastric bypass) experienced a weight loss of around 31%, their rate of any cancer diagnosis was only 23% of that in the control group (77% risk reduction!). The biggest risk reductions were seen for breast (83%) and colorectal (68%) cancers. Thus, while bariatric surgery has long been documented to remarkably improve a host of obesity-related disorders including type 2 diabetes, dyslipidemia, heart disease, sleep apnea, osteoarthritis and pain, the reduction in cancer morbidity and mortality has perhaps been less well recognized. I wonder just how much the “Run for the Cure” has contributed to research on obesity and bariatric surgery to date? AMS Edmonton, Alberta
Adiponectin Gene Links Obesity to Colon Cancer?
As regular readers of this blog should know by now, obesity is associated with increased risk for cancers. While the reason for this may be seemingly straightforward for cancers linked to sex hormones affected by excess weight such as breast or endometrial cancers, how exactly does this work for colon cancer? According to a new study just out in JAMA, the missing link may well be the adipocyte-derived hormone adiponectin, levels of which are well-known to be reduced in obese individuals. Following previous reports on an association between circulating adiponectin levels and colorectal cancer risk, Virginia Kaklamani from the University of Alabama, Birmingham, and collaborators examined the relationship between genetic variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer. Based on the DNA analysis of participants in two independent case-control studies together including around 600 patients with a diagnosis of colorectal cancer and an equal number of matched controls, the researchers found significant associations between genetic variants of these genes and colorectal cancer risk. Specifically (for geneticists who happen to read these lines), the SNP rs266729, which tags the 5′ flanking region of the ADIPOQ gene, was associated with decreased colorectal cancer risk. This study of course does not reveal the exact mechanism of the link. Although adiponectin receptors are present in colon mucosa, adiponectin may also act indirectly by influencing levels of insulin or insulin-like growth factor (IGF1). So what does this mean? Firstly, the strength of the association is hardly enough to warrant a diagnostic test for colorectal cancer risk based on this gene. Secondly, just because adiponectin levels are inversely related to cancer risk, does not necessarily mean that simply raising adiponectin levels (for e.g. through weight loss) will help prevent colon cancer (although we do know that weight loss reduces cancer risk). Thirdly, as noted above, the study does not actually provide any new insights into a mechanistic link that directly explains how this genetic variant possibly leads to carcinogensis in colon cells. So why bother writing about this? Well for one, adiponectin is of special interest to anyone studying obesity, as it appears to be one of the key factors linking excess adipose tissue to increased risk for diabetes and heart disease. Secondly, tying in adiponectin (or rather lack of it) to cancer risk, to me at least, is a rather novel concept that I will certainly be following closely in the… Read More »
Obesity Predicts Poorer Prognosis in Breast Cancer
Not only is obesity a major risk factor for breast cancer, it is also associated with poorer outcomes. The reason for this relationship is unclear and was recently examined by Jennifer Litton and colleagues from the The University of Texas, Houston, TX (Journal of Clinical Oncology). Specifically, these researchers studied the relationship between BMI and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Neoadjuvant chemotherapy refers to drug treatment given to people with cancer prior to surgery in the hope of reducing the size of the cancer, thus making surgery easier and more likely to be successful. From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at the M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese, overweight, or normal/underweight. Logistic regression was used to examine associations between BMI and pathologic complete response, defined as the complete absence of intact tumour cells in the resected specimen (a marker of good prognosis). While 30% of patients were obese, 32% were overweight, and 38% were normal or underweight, overweight and obese patients were around 30 to 40% less likely to have a pathologic complete response. Interestingly, obese patients were also more likely to have hormone-negative tumors, stage III tumors, and significantly worse overall survival at a median follow-up time of 4.1 years. The authors conclude that obesity is not just a risk factor for breast cancer but also a risk factor for poorer response to neoadjuvant chemotherapy as well as worse overall survival. They suggests that greater attention should be focused on obesity management to optimize the care of breast cancer patients. Remember, at least in surgical studies, weight loss is associated with a 60% reduction in cancer deaths. AMS Edmonton, Alberta
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