Smoking has been the No. 1 preventable cause of cancer for decades and still kills more than 500,000 people a year in the United States. But obesity is poised to take the top spot, as Americans’ waistlines continue to expand while tobacco use plummets.

The switch could occur in five or 10 years, said Otis Brawley, a Johns Hopkins oncologist and former chief medical officer of the American Cancer Society. The rise in obesity rates could threaten the steady decline in cancer death rates since the early 1990s, he said.

Yet only about half of Americans are aware of the link between excess weight and cancer. And researchers are struggling to answer such fundamental questions as how surplus weight increases the risk of the disease and whether, conversely, losing weight helps prevent cancer or a recurrence.

Being obese or overweight — long implicated in heart disease and diabetes — has been associated in recent years with an increased risk of getting at least 13 types of cancer, including stomach, pancreatic, colorectal and liver malignancies, as well as postmenopausal breast cancer. American Cancer Society researchers say that excess body weight is linked to about 8% of all cancers in the U.S. and about 7 % of cancer deaths.

Compared with people of normal weight, obese patients are more likely to see their cancer come back and have a lower likelihood of survival. Perhaps most alarming, young people, who as a group are heavier than their parents, are developing weight-related malignancies, including colorectal cancer, at earlier ages than previous generations, experts say.

The precise link between cancer and excess weight isn’t known, but researchers are focusing on the “visceral” fat that surrounds internal organs. Rather than being a harmless glob, this fat is a “metabolically active organ” that produces hormones such as estrogen, which is associated with a higher risk of breast and some other cancers, according to the American Institute for Cancer Research, a nonprofit that focuses on diet, nutrition and cancer.

The fat also secretes proteins that drive insulin levels higher, which may spur cell growth and increase the cancer risk. And it can cause chronic inflammation, another risk factor.

“It’s a complex interplay of metabolism, inflammation and immunity,” said Jennifer Ligibel, a breast oncologist at the Dana-Farber Cancer Institute in Boston. “It creates an environment that is more permissive for cancer.”

About 7 in 10 Americans are overweight or obese, according to a 2015 article in JAMA Internal Medicine. People are considered overweight if they have a body mass index (BMI) of 25 to 29, and obese if they have a BMI of 30 or more.

The proportion of adults who are overweight has remained relatively stable in the past several decades, but the obesity rate has soared.

The cancer risk rises along with excess weight. “It does appear that the risk is greater the more obese you are,” said Jonathan Wright, a urologist at Fred Hutchinson Cancer Research Center in Seattle.