How high blood sugar, hypertension and obesity can add up to cancer risk

About a third of Americans have metabolic syndrome. It's a cluster of conditions that can include hypertension, high blood sugar and a large waistline, and together increase your risk of heart disease, stroke and Type 2 diabetes.

New research underscores another potential consequence: Cancer.

The link between cancer and having excess body fat is well-established.

But this latest study, published in the journal Cancer, takes a broader look at this relationship, focusing on how metabolic syndrome in general raises the risk of developing a variety of cancers.

"There's a lot of concern that this is going under the radar, at least with American public health, that we're not really fully grasping the risks," says Gerald Denis, a molecular oncologist at Boston University.

The research team, based in China, studied more than 40,000 people with some or all of five factors of metabolic syndrome: hypertension; low levels of HDL, i.e., "good cholesterol," elevated triglycerides, high blood sugar, and a large waistline. Metabolic syndrome is defined as having at least three of these conditions.

After measuring their metabolic health over four years, researchers then tracked who developed cancer over about a decade. The participants, on average, were about 50 years old.

Those with metabolic syndrome had a 30% increased risk of developing any cancer in the subsequent years, the study showed.

"It's very compelling," says Denis, who wasn't involved in the study. "They're seeing that as you cluster these factors, risk goes up which makes perfect sense to me."

The researchers also tracked C-reactive protein, which is used to measure chronic inflammation. Metabolic syndrome and higher levels of this protein were "significantly associated with subsequent breast, endometrial, colorectal and liver cancers," the authors conclude.

Denis says this ties into the broader evidence base that points to "chronic smoldering inflammation" as a key factor associated with these cancers.

The overall findings reflect what others in the field are seeing when they drill down on the link between cancer and metabolic syndrome.

"We're observing a very similar 30% increased risk," says Maci Winn, an MD/PhD student at the University of Utah's Huntsman Cancer Institute, who recently completed a review of the existing evidence, which has not yet been published.

The large number of people enrolled, the prospective design and its "robust assessment of metabolic parameters" are all strengths of the new study, says Sheetal Hardikar, an investigator at the Huntsman Cancer Institute who was not involved in research.

But she says it's important to tease apart all the metabolic risk factors.

The study used a definition of metabolic syndrome that required a person to have a large waistline – what the researchers called "central obesity" – plus two other conditions. So it couldn't answer to what extent the cancer risk was associated with the other conditions that are part of metabolic syndrome, independent of their waistline.

Hardikar's lab studies this topic. "In our research, we found that metabolically unhealthy, but normal weight patients also have an increased risk for cancer," she says.

She says there's evidence that this group actually has a higher cancer risk than those who are considered to have obesity, but have okay metabolic health based on their blood tests.

"That's where the mechanisms are not very well understood," she says, "It's not just your BMI, but where your fat is distributed and how metabolically active it is."

In future research, Winn says the hope is to more precisely identify which conditions raise someone's risk, and by how much, when they have a constellation of metabolic problems.

"We do know that there are at least 13 cancers that are causally-related to obesity. But there are other things like [high blood sugar], hypertension that may also be contributing," she says.

Researchers have moved away from relying on BMI because it's a "terrible" measure of risk, says Denis. And he points out that the Chinese population in this study tends to have an overall lower BMI from what you see among patients in the U.S.

"These are people who are fairly lean, their BMIs are not that high, but they're very metabolically disordered and their cancer risks are in fact higher," he says.

This raises a concern about "metabolism-driven cancers in Asia and South Asia, where diabetes is exploding in prevalence, but not necessarily in conjunction with morbid obesity."

The research may have been done in China, but Hardikar says it has clear lessons for the U.S. where doctors need to pay attention to all risk factors holistically, "looking at them in conjunction versus in isolation."

A final question that doesn't get addressed in the current study: What happens to patients with metabolic syndrome when they get cancer treatment?

"Because we know they don't do as well. And so why is that?" Denis says, "I don't think we understand."

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