Obesity Impact Draws Increased Scrutiny in GI Malignancies

Hisham Hussan, MD

Obesity is associated with an increased risk of early-onset colorectal cancer (CRC) among women and correlates with higher rates of cancer resections in gastrointestinal (GI) malignancies across age groups, according to recent research findings.

In findings published in JAMA Oncology, investigators reported that the risk for developing CRC before age 50 years is nearly double for women who are obese and elevated for those who are overweight compared with women with a normal body mass index (BMI).¹

Meanwhile, rates of resection were higher among obese patients with CRC as well as gastric, pancreatic, and esophageal cancers than they were for nonobese patients and, in some of these GI cancer types, were increasing more rapidly, investigators reported at the 2018 American College of Gastroenterology (ACG) Annual Meeting.²

The latest study findings in GI cancers come at a time of increasing concern over the role that obesity plays in multiple tumor types. In an analysis published earlier this year, American Cancer Society researchers said that excess body weight accounts for the second-highest proportion of cancer cases and deaths attributable to potentially modifiable risk factors after cigarette smoking.³

At the same time, epidemiologists have been noting with alarm that younger people are increasingly likely to be diagnosed with GI malignancies. In colon cancer, overall incidence and mortality have been declining since the 1980s; however, population-based projections suggest colon cancer incidence is expected to increase by 90% among adults aged 20 to 34 years and by 28% among those aged 35 to 49 years by 2030. The incidence of rectal cancer is expected to increase by 124% among those aged 20 to 34 years and by 46% among those aged 35 to 49 years.¹

Body Mass Characterized

Incidence of early-onset CRC, defined as diagnoses in adults younger than 50 years, remains rare at approximately 8 per 100,000 individuals, but accounts for at least 10% of total CRCs that are not prevented or detected through screening.¹To date, investigators have not been able to identify the factors contributing to the increase in early-onset disease. Led by epidemiologists at Washington University School of Medicine in St. Louis, Missouri, investigators sought to examine the association between obesity, weight gain, and CRC. They analyzed data from the Nurses’ Health Study II, an ongoing study of female nurses (N = 85,256) in the United States who were free of cancer and inflammatory bowel disease when they enrolled in the study in 1989. The findings showed that the risk for developing CRC before age 50 years is nearly double for women who were obese, defined as a BMI ≥30.0, compared with those with a BMI of 18.5 to 22.9.

Compared with women who had a BMI of 18.5 to 22.9, the relative risk (RR) for early-onset CRC was 1.93 (95% CI, 1.15-3.25) for obese women and 1.37 (95% CI, 0.81-2.30) for overweight women. The RR for women with a BMI of 23.0 to 24.9 was 1.33 (95% CI, 0.75-2.36). Investigators observed a direct correlation between higher BMI and increased risk. The RR for every 5-unit increase in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend).

Cosenior author Yin Cao, ScD, a cancer epidemiologist and assistant professor of surgery in the Division of Public Health Sciences at Washington University in St. Louis, estimated that 22% of early-onset CRCs could be prevented if all women in the study had a BMI between 18.5 and 24.9.

“Our findings really highlight the importance of maintaining a healthy weight, beginning in early adulthood, for the prevention of early-onset colorectal cancer,” she said in a statement. “We hypothesized that the obesity epidemic may partially contribute to this national and global concern in early-onset colorectal cancer rates, but we were surprised by the strength of the link and the contribution of obesity and weight change since early adulthood.”

In this observational study, investigators detected 114 cases of early-onset disease during nearly 1.2 million person-years of follow-up. The median age at diagnosis was 45 years (interquartile range, 41-47). Women in the study were disease free at enrollment and aged from 25 to 42 years. Participants were followed from 1989 through 2011.

Women with a higher current BMI tended to be older and less likely to engage in physical activity. These women also consumed more red meat and were more likely to have diabetes, and their current BMI correlated with the BMI at age 18 (Pearson correlation coefficient, 0.55).

The research team found that the association between current BMI and risk for early-onset CRC was consistent even after restricting the analysis to women with no family history of CRC or to those who had not undergone lower endoscopy within the past 10 years. Investigators also evaluated the association between current BMI, BMI at age 18, and weight gain since age 18. Risk for earlyonset CRC was associated with both BMI at early adulthood and change in weight since early adulthood. Women with a BMI ≥23.0 at age 18 were at increased risk for early-onset disease compared with women in the lowest BMI cohort (RR, 1.63; 95% CI, 1.01-2.61; P = .66 for trend).

Women with a BMI of 23.0 or greater at 18 years of age and weight gain of 20.0 kg or more had the highest risk of early-onset CRC. Compared with women who lost weight or gained >5.0 kg since age 18, the RR was 1.65 (95% CI, 0.96-2.81) for women who gained 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for those who gained ≥40.0 kg. RR was 1.09 (95% CI, 1.02-1.16; P = .007 for trend) for every 5.0-kg increase in weight.

Body shape during childhood and adolescence and change in body shape during early life were not associated with risk for early-onset disease. However, investigators did observe a correlation between body shape during early adulthood and early-onset CRC. RR was 1.71 (95% CI, 1.01-2.89) for women with a pictogram of ≥4 (more obese) compared with those with a pictogram of ≤2 (leaner) at age 20 years. Current BMI was associated with risk for early-onset disease, but not CRC diagnosed at age ≥50 (P = .38 for trend).

Table. Incidence of Resection Among Patients With Colorectal and Gastric Cancers²

Resection Trends Analyzed

Investigators said the study is among the first to delve into the association between obesity and early-onset CRC, but said that further research is needed. “Emerging data also suggest that early-onset colorectal cancer may be different on a molecular level from cases diagnosed at older ages,” Cao said. “Because early-onset colorectal cancer is rare, we need more collaborative research to understand why case rates and deaths among younger people are increasing and what could be done to slow them down.”For their study, investigators at The Ohio State University Wexner Medical Center in Columbus analyzed information collected in the Surveillance, Epidemiology, and End Results (SEER) Program and the National Inpatient Sample (NIS) databases. Lead author Hisham Hussan, MD, presented the findings at the ACG conference, which was held October 5 to 10 in Philadelphia, Pennsylvania. He is an assistant professor and director of the Obesity and Bariatric Endoscopy section of the Division of Gastroenterology, Hepatology & Nutrition, at Wexner.

Previous study data, Hussan noted, have shown an association between GI cancers and obesity, but researchers have not described how the rising incidence of obesity affects the incidence obesity-related GI cancers over time.

“We identified an alarming temporal increase in the incidence of young-onset, less than 50 [years], colon, and gastric cancers during the study period from 2002 to 2013,” Hussan said. “There was a corresponding pronounced increase in rates of obese patients undergoing cancer resections.”

Investigators analyzed SEER to identify incidence and trends of esophageal, gastric, pancreatic, and CRC cancers and reviewed NIS data for obesity and cancer resection rates. Outcomes of interest included age-stratified results for incidence of obesity-related GI cancers and rates of surgical resection stratified by obesity. Investigators then calculated the average annual percentage change (APC) using join point regression analysis. Patients were stratified into groups aged 18 to 49 years, 50 to 64 years, 65 to 74 years, and ≥75 years.

A total of 91,116 (7.16%) obese and 1.18 million (92.8%) nonobese adults included in the study underwent resection from 2002 to 2013, most often for CRC (93.1%) or gastric cancer (4.4%). Overall, the number of obese patients (BMI ≥30) per 100,000 individuals with CRC or gastric cancer who underwent resections increased in all age groups over the study period (Table).² The greatest increases were observed in those with CRC aged 18 to 49 years, with an average APC over time of 13.1% (P <.001), and in patients ≥75 years with gastric cancer, who had an APC of 15.3% (P <.001).² By contrast, there was a decrease in cancer resections in nonobese patients with those cancers.

Although rates of pancreatic cancer resections declined by 3.9% among obese patients aged 18 to 49 years, the incidence of these surgeries increased by 27.6% among those aged 65 to 74 and by 26.9% among those aged 50 to 64 years. Resections among nonobese patients increased for all age groups, with the greatest increase coming in the patients aged 75 or older (9.7%). The resection rate among the youngest cohort increased by 2.1%.

Among obese patients who underwent esophageal resection, rates increased across the board. Rates went up by 25.7% in those aged 65 to 74, 14.6% among those aged 50 to 64 years, 11.2% in the 18-to-49 age group, and 1.0% among those 75 or older. Among nonobese patients, the rate decreased by 0.7% among the youngest cohort, but increased for the other age cohorts.

In terms of cancer incidence, trends identified in the study showed a similar pattern as those in the JAMA Oncology research. CRC increased by 1.5% (P <.05), an average APC of 15% per year, for adults between 20 and 49 years during the study period but declined across the other age groups. Similarly, gastric cancer incidence increased in this cohort by an average APC of 0.7% annually (P <.05) while declining for other age groups. Incidence of esophageal cancer decreased across all age groups while the occurrence of pancreatic cancer increased slightly across all age groups.

Hussan noted that these results provide evidence of the role of obesity in etiology and the increasing incidence of some GI cancers in younger people. He called for more obesity prevention initiatives. He went on to say that the effect of obesity may be greater than these data suggest. “Obesity was defined by BMI at the time of surgery, so some patients may have lost weight before surgery due to cachexia,” he said. “However, we see an increase in obese patients undergoing resection, so [the effect] could have been more pronounced if we accounted for obesity at diagnosis.”

References

1. Liu PH, Wu K, Ng K, et al. Association of obesity with risk of early-onset colorectal cancer among women [published online October 11, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.4280.
2. Hussan H, Pavurala R, Porter K, et al. Rising, age-specific, trends of obesity-related gastrointestinal cancers correspond with increasing cancer resections in obese patients: a 2002-2013 national analysis using the SEER and NIS databases. Presented at: the 2018 ACG Annual Meeting; October 5-10, 2018; Philadelphia, Pa. Abstract 34. eventscribe.com/2018/ACG/fsPopup.asp?Mode=presInfo&PresentationID=442144.
3. Islami F, Goding Sauer A, Miller KD, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin. 2018;68(1):31-54. doi: 10.3322/caac.21440.