Dr. Sharma's Obesity Notes

Head Domain of Adiponectin

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 future.

AMS
Edmonton, Alberta

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

Yes, there’s a childhood and adolescent obesity epidemic out there. The word on the street now is that “this is the first generation of kids, who will not outlive their parents”.

But is this really true? Where is the data showing that childhood obesity is really a risk factor for early death?

This question is now answered by perhaps the largest study on this issue to date published by Tone Bjørge and colleagues from the University of Bergen, Norway, in the American Journal of Epidemiology.

Bjørge and colleagues studied the relationship between BMI (measured height and weight) and mortality in 227,000 adolescents (aged 14-19 years) recruited in Norwegian health surveys in 1963-1975. During follow-up (8 million person-years), 9,650 deaths were observed. Cause-specific mortality was compared among individuals whose baseline BMI was below the 25th percentile, between the 75th and 84th percentiles, and above the 85th percentile in a US reference population with that of individuals whose BMI was between the 25th and 75th percentiles.

Risk of death from endocrine, nutritional, and metabolic diseases and from circulatory system diseases was increased in the two highest BMI categories for both sexes. Relative risks of ischemic heart disease death were 2.9 for males and 3.7 for females in the highest BMI category compared with the reference. There was also increased risk of death from colon cancer (males: 2.1; females: 2.0), respiratory system diseases (males: 2.7; females: 2.5), and sudden death (males: 2.2; females: 2.7).

The authors conclude that adolescent obesity is related to increased mortality in middle age from several important causes.

Clearly not a good sign for what awaits our sons and daughters unless we get a hold on the obesity crisis.

AMS
Edmonton, Alberta

We know now (although many still do not fully appreciate this) that obesity is a major risk factor for cancers. On the other hand in patients with many chronic diseases, larger patients tend to do better and live longer (the obesity survival paradox).

Last week researchers from the University of Alberta published a study in The Lancet Oncology, that adds another level of complexity to the relationship between obesity and cancer survival. Clarisse MirandaPrado together with other researchers from the UofA, including cancer cachexia researchers Vickie Baracos, studied 2115 patients with solid tumours of the respiratory or gastrointestinal tract, 325 (15%) of who were classified as obese (body-mass index [BMI] >/=30).

With the help of CT images, the researchers found that obese patients had a wide range of muscle mass, with 15% of analysed obese patients meeting criteria for “sarcopenic” obesity (sarcopenia is the medical term for low-muscle mass). By definition, sarcopenic obese patients have more body fat and less lean body mass than non-sarcopenic patients of similar weight.

Not only was sarcopenic obesity associated with poorer functional status compared with non-sarcopenic obese patients but these patients also had a 4-fold hgher risk of dying.

Incidentally, the researchers also used their data to calculate that using conventional dosing criteria for cytotoxic chemotherapeutic drugs, sarcopenic obese patients may be overdosed with a greater likelihood of toxicity.

Overall this study shows that obesity is never just obesity and that BMI in the clinic is a fairly useless concept (a point that I have argued before) and that without proper assessments of body composition rational management of large patients is just not possible.

A patient’s size alone proves little in term of health or disease - remember, weight alone is a rather poor measure of health.

AMS
Edmonton, Alberta

Looks like this week is about obesity and men’s health. So after blogging about male self-esteem and erectile dysfunction, what about obesity and risk for prostate cancer?

Well, after a quick search of the literature, I can happily state that the data on this is pretty inconsistent.

Probably the best study, a prospective cohort study in 34,754 men residing in Washington State (aged 50-76 years at baseline) studied by Alyson Littman and colleagues from the Fred Hutchinson Cancer Research Center, Seattle, WA, published in the American Journal of Epidemiology, succeeded in confusing me more than providing any definitive answers.

Thus, while on one hand obese men had a reduced risk of nonaggressive disease, overweight (but not obese) men, had an increased risk of aggressive disease. Body mass index of >25 at age 18 years was associated with increased risk of aggressive prostate cancer; obesity at ages 30 and 45, but not 18, years was associated with reduced risk of nonaggressive prostate cancer.

I can only concur with the authors, who conclude that this study demonstrates the complexity of prostate cancer epidemiology and the importance of examining risk factors by tumor characteristics.

So is obesity a significant risk factor for prostate cancer? I guess the answer is “depends”.

AMS
Edmonton, Alberta