Obesity Underlies the Rise in US Papillary Thyroid Cancers

Miriam E. Tucker

March 29, 2019

NEW ORLEANS — By 2015, one of every six papillary thyroid cancers (PTC) and two thirds of all large PTC tumors in the United States were attributable to overweight or obesity, new research indicates. 

An analysis of data from three large national US databases was presented March 25 here at ENDO 2019: The Endocrine Society Annual Meeting by Cari M. Kitahara, PhD, an investigator at the National Cancer Institute (NCI).

"The extent of the impact of obesity was what we expected for overall PTC but we were surprised it was so large for the tumors that were over 4 cm in diameter," Kitahara told Medscape Medical News in an interview.

She added, "We may not be seeing these tumors [earlier] because it's more difficult to detect them in these patients until they're a certain size. But [the findings are] consistent with the idea that obesity is involved in the promotion and the growth of tumors. It might be associated with a more aggressive phenotype."

Asked to comment, session comoderator Trevor E. Angell, MD, assistant professor of clinical medicine in the division of endocrinology, diabetes, and metabolism at the Keck School of Medicine of the University of Southern California, Los Angeles, said that although the link between obesity and PTC has been described previously, "this has been in smaller and less robust methodological ways."

He praised Kitahara's use of large datasets and statistical adjustments for many potentially confounding variables.

Such an approach, he said, "improves our confidence that there really is this relationship."

However, he said that despite the strong evidence of a link between the rising rates of PTC and of obesity, "at the same time we see that this isn't just an obesity-related phenomenon. We're still seeing the big increase that we attribute to more surveillance or more detection bias."

Thyroid Cancer Rise Parallels Obesity Epidemic

The incidence of thyroid cancer in the United States rose 3.5-fold between 1980 and 2015, from 6.0 to 22.3 per 100,000 in women and 2.1 to 7.6 per 100,000 in men. Nearly all of the increase has been driven by papillary histologic types, Kitahara noted.

A previous study from her NCI group found that increases have occurred for tumors of all sizes and stages, and that thyroid cancer mortality is also increasing, suggesting that "increased diagnosis is not the sole explanation and that environmental and lifestyle factors may have played a role."

The obesity epidemic has been happening at the same time to the point now that 40% of US adults are obese. Growing evidence from epidemiologic, clinical, and laboratory-based studies suggests a link between the two phenomena, she said.

Strong Link Found Between Obesity and Large PTC Tumors

For this study, Kitahara and colleagues analyzed data from the National Institutes of Health-AARP Diet and Health Study, National Health Interview Survey, and Surveillance, Epidemiology, and End Results (SEER) program.

During follow-up from 1995-1996 to 2011, they identified 824 primary thyroid cancers including 604 incident PTC tumors. After adjustment for age, sex, race/ethnicity, education, smoking status, and alcohol intake, the PTC risk increased with greater body mass index (BMI). Compared to a BMI 18.5-24.9 kg/m2, total PTC relative risk was 1.26 for a BMI 25.0-29.9 kg/m2 and 1.30 for a BMI of 30 kg/m2 and higher. There was no relationship by PTC stage at diagnosis.

No significant relationship was found between BMI and PTC risk for tumors less than 4 cm in diameter.

However, among just the 50 PTCs larger than 4 cm, there was a strong relationship, with a relative risk of 2.93 for BMI 25.0-29.9 kg/m2 and 5.42 for 30 kg/m2 and above (compared with a BMI 18.5-24.9 kg/m2).

There are several possible interpretations of these findings, Kitahara said.

First, there may be delayed tumor detection in the obese group because of greater challenges in detection via palpation or imaging, so the tumor may not be apparent until it grows larger.

Alternatively, surveillance and detection might be greater in those with lower BMIs.

Thirdly, obesity may exert a direct influence on tumor growth and progression. Data on the latter have been inconsistent, she noted.  

Indeed, Angell pointed out that more information is needed, such as how these individuals were diagnosed or whether they had good access to care.

Could Thousands of PTCs Be Preventable?

Next, Kitahara and colleagues estimated the population-attributable fraction (PAF), or percentage of PTC cases that would not have occurred without exposure (ie, obesity).  

Assuming a 10-year latency period, the population-attributable fraction of PTC because of overweight/obesity rose from 11% in 1985-1997 to 16% in 2013-2015.

For PTCs larger than 4 cm, the rise was from 51% to 63%. This works out to an excess of about 7500 total PTCs and 2350 large PTCs that could have been avoided, Kitahara said.

"Broad-based interventions on the population level designed to curb obesity in the population may have the added benefit of reducing the incidence of PTC among many other health benefits," she concluded.

Angell commented, "This is another good reason...to encourage people to attain a healthy weight."

Kitahara and Angell have reported no relevant financial relationships.

ENDO 2019. Presented March 25, 2019. Abstract OR27-4.

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