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CME / ABIM MOC / CE

Is Obesity-Related Risk for GI Cancers Sex-Dependent?

  • Authors: News Author: Sharon Worcester; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 4/8/2022
  • Valid for credit through: 4/8/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for hematologists/oncologists, gastroenterologists, family medicine and primary care practitioners, internists, nurses, and other members of the healthcare team for patients with or at risk for gastrointestinal (GI) cancers.

The goal of this activity is for learners to be better able to describe the association between pre-obesity and obesity and the risk for GI cancer development in male and female patients, according to an analysis of the Disease Analyzer database (IQVIA), a large outpatient database from Germany.

Upon completion of this activity, participants will:

  • Describe the association between pre-obesity and obesity and the risk for GI cancer development in male and female patients, according to an analysis of IQVIA, a large outpatient database from Germany
  • Identify clinical implications of the association between pre-obesity and obesity and the risk for GI cancer development in male and female patients, according to an analysis of IQVIA
  • Outline implications for the healthcare team


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News Author

  • Sharon Worcester

    Freelance writer, Medscape

    Disclosures

    Disclosure: Sharon Worcester has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie (former)

Editor/Compliance Reviewer

  • Lisa Simani, APRN, MS, APRN

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure:  Lisa Simani, APRN, MS, APRN, has disclosed no relevant financial relationships.

Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.


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CME / ABIM MOC / CE

Is Obesity-Related Risk for GI Cancers Sex-Dependent?

Authors: News Author: Sharon Worcester; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 4/8/2022

Valid for credit through: 4/8/2023

processing....

Clinical Context

Cancer is the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight and obesity, both of which are dramatically on the rise in both highly and less developed regions worldwide, have been established as modifiable risk factors for the development of various tumor entities including gastrointestinal (GI) cancers such as colorectal or gastric cancer.

Several gastrointestinal (GI) cancers (e.g. colorectal, gastric, esophagus and liver cancer) are among the 10 most prevalent tumors worldwide in both sexes, and most have high morbidity and mortality. Primary prevention of cancer based on established risk factors is a leading strategy to reduce the high number of cancer-associated deaths worldwide.

In addition to genetic alterations associated with increased risk for cancer development, several modifiable risk factors for cancer have been identified in recent decades. Among these, overweight and obesity, which are dramatically on the rise in both highly and less developed regions worldwide, represent a crucial risk factor for cancer development. Although the underlying pathophysiological mechanism have not been fully elucidated today, several studies have proven an association between pre-obesity or obesity and an increased risk for cancer development for different cancer entities including post-menopausal breast cancer, cervix, and ovarian cancer and renal cell carcinoma. In line, there is a growing body of evidence suggesting an association between excessive body fat and the incidence of GI cancers such as colorectal cancer, gastric cancer, liver cancer, and pancreatic cancer.

Study Synopsis and Perspective

Weight-related risk for GI cancers is driven in part by sex, a retrospective study of more than 287,000 outpatients in Germany suggests.

The results show, for instance, that obesity increases the risk for colon cancer in both men and women but increases the risk for rectal and liver cancers in men only.

"Our data suggest that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner," Sven H. Loosen, MD, of Heinrich Heine University, Duesseldorf, Germany, and colleagues wrote.

The study was published February 13 in Cancers.[1]

Among 287,357 adults from the Disease Analyzers database, Loosen and colleagues compared the development of GI cancers in individuals with pre-obesity (body mass index [BMI] = 25-29 kg/m2) and obese (BMI ≥ 30 mg/m2) to that of individuals of normal weight (BMI = 18.5-24 kg/ m2).

For colon cancer, the authors observed a stepwise increase in the proportion of diagnoses, from 0.5% and 0.64% in women and men of normal weight, respectively, to 0.71% and 0.91% in women and men with obesity, respectively. In multivariable regression models, that translated to a significantly increased risk for colon cancer in women with obesity (odds ratio [OR] = 1.23 [95% CI: 1.03, 1.48]) and men with obesity (OR = 1.43 [95% CI: 1.17, 1.74]).

Multivariable regression models, however, showed that associations between obesity and rectal and liver cancers occurred only in men (ORs = 1.36 and 1.79, respectively).

Notably, the authors also observed a negative association between pre-obesity and stomach cancer in men (OR = 0.65) and obesity and pancreatic cancer in women (OR = 0.61).

In other words, women and men with excess body fat may be "protected" from developing these conditions, "highlighting the complexity of the association between BMI and cancer in the different sexes," the authors wrote.

These findings could have implications for prevention and lifestyle programs, the authors said.

"Since pre-obesity and obesity are modifiable risk factors, the current results may help to establish appropriate prevention and lifestyle programs to reduce the high morbidity and mortality of GI tumors in the future," they concluded.

They suggested that some "overweight patients might be presented in a specific interdisciplinary 'metabolic board' comprising oncologists and physicians specialized in preventive medicine."

No specific funding related to this study has been disclosed. The authors have disclosed no relevant financial relationships.

Cancers (Basel). 2022;14:931.[1]

Study Highlights

  • Using the IQVIA database, the researchers identified 287,357 adult outpatients with an available BMI value between 2010 and 2019.
  • The main outcome was the association between pre-obesity (BMI = 25-29 kg/m2) and obesity (BMI ≥ 30 kg/m2) vs normal weight (BMI = 18.5-24 kg/m2) and incident GI cancer diagnoses (colon, rectum, stomach, pancreas, and liver cancer).
  • The proportion of patients with colon cancer increased stepwise from 0.5% and 0.64% in normal weight to 0.71% and 0.91% in female and male patients with obesity, respectively.
  • Multivariable regression models showed the ORs for colon cancer were 1.23 (95% CI: 1.03, 1.48) for female obesity and 1.43 (95% CI: 1.17, 1.74) for male obesity.
  • In contrast, obesity was significantly associated with rectal cancer (OR = 1.36 [95% CI: 1.01, 1.84]) and liver cancer (OR = 1.79 [95% CI: 1.17, 2.73]) in men only.
  • There were negative associations between pre-obesity and stomach cancer in men (OR = 0.65 [95% CI: 0.48. 0.87]) and obesity and pancreatic cancer in women (OR = 0.61 [95% CI: 0.45, 0.82]).
  • The investigators concluded that obesity is a significant risk factor for development of colon, rectal, and liver cancer, partly in a sex-dependent manner.
  • As overweight and obesity are modifiable risk factors, these findings may inform appropriate prevention and lifestyle programs to lower the incidence of GI tumors in the future, as well as the accompanying high morbidity and mortality.
  • Primary prevention of tumorigenesis should include obesity avoidance and treatment.
  • Combined with previous data, the findings suggest that clinical management of patients with overweight should include careful, structured risk assessment for cancer development to improve long-term outcomes in these patients.
  • Notably, excess body fat may be protective against stomach cancer in men and pancreatic cancer in women, reflecting the complexity of the association between BMI and cancer in men and in women.
  • Patients with overweight might benefit from review by a specific interdisciplinary metabolic board, including oncologists and preventive medicine physicians.
  • Possible mechanisms linking obesity and pre-obesity to cancer may include adipose tissue as an important source of hormones (adipokines); growth factors; and inflammatory cytokines, including tumor necrosis factor-α and interleukin-6.
  • These acute phase proteins stimulate the liver to produce and secrete other inflammatory ligands, triggering general and tumor-type-specific carcinogenic effects.
  • Adipose tissue is also involved in production and metabolism of estrogens and other hormones, which may be relevant to sex-specific effects of obesity on cancer.
  • Previous studies showed lower incidence of colorectal cancer in postmenopausal women without obesity taking hormone replacement therapy, and an association of microsatellite instable high colorectal cancer in obese men but not women.
  • Significant differences in adipose tissue distribution and composition among male and female individuals might result in differential effects of obesity even on non--sex-specific cancers.
  • Distribution of gut microbiota, which is an important risk factor for development of GI cancers, also varies according to sex.
  • As the gut microbiome is involved in excretion and circulation of sex hormones, various experts have suggested the concept of "microgenderome" to illustrate the complex interplay of the microbiome and sex hormones that could trigger the development of cancer in only one sex.
  • The patients' sex should therefore be considered in possible strategies to lower the high morbidity and mortality of GI tumors, such as nutraceutics, Mediterranean diets, and/or functional foods.
  • The global burden of cancer attributable to obesity, or population-attributable fraction, is 11.9% among men and 13.1% among women.
  • Another study showed that in 2014 in the United States, excess body weight accounted for 36% of gallbladder cancers, 34% of liver cancers, 32% of esophageal cancers, 17.5% of gastric cancers, and 17% of pancreatic cancers in adults aged ≥ 30 years.
  • The positive dose-response association between excessive body weight and the risk for those cancers is in keeping with findings of the present study.
  • Study limitations include diagnoses recorded as International Classification of Diseases, Tenth Edition codes, which might lead to misclassification; incomplete data for some patients; lack of data on socioeconomic and lifestyle-related risk factors; and selection bias, as patients with obesity may have more frequent physician contacts and comorbidities than patients of normal weight.
  • In addition, small sample sizes precluded subgroup analyses of individual cancer sites or subtypes.
  • Although the underlying pathophysiological mechanism have not been fully elucidated today, several studies have proven an association between pre-obesity or obesity and an increased risk for cancer development for different cancer entities including post-menopausal breast cancer, cervix, and ovarian cancer and renal cell carcinoma.

Clinical Implications

  • Obesity is a significant risk factor for development of colon, rectal, and liver cancer, partly in a sex-dependent manner, shows an analysis by Loosen and colleagues of a large outpatient database.
  • As overweight and obesity are modifiable risk factors, these findings may inform appropriate prevention and lifestyle programs to lower the incidence of GI tumors in the future, as well as the accompanying high morbidity and mortality.
  • Implications for the Healthcare Team: Primary prevention of tumorigenesis should include obesity avoidance and treatment.

 

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