Body weight link to breast and endometrial cancers (and 11 others)

 

A new analysis reveals that the cancer burden from overweight/obesity is greater than previously reported. The International Agency for Cancer Research (IARC) of the World Health Organization (WHO) reported that sufficient evidence exists to link high BMI to 13 different cancers, including endometrial and postmenopausal breast cancers.[1] In addition, it may be that the risks for obesity-related cancers may compound over time.[2]

The IARC reviewed more than 1,000 studies looking at the association between weight and cancer risk.¹ Several years ago, the IARC had found a link between greater BMI and 8 different cancers.  In this newest review, the group found sufficient evidence to link body weight/BMI to 14 cancers:

Cancer site or type	Relative risk of highest BMI to normal BMI
Corpus uteri	7.1 [6.3-8.1]
Esophagus: adenocarcinoma	4.8 [3.0-7.7]
Gastric cardia	1.8 [1.3-2.5]
Liver	1.8 [1.6-2.1]
Kidney: renal cell	1.8  [1.7-1.9]
Pancreas	1.5 [1.2-1.8]
Meningioma	1.5 [1.3-1.8]
Multiple myeloma	1.5 [1.2-2.0]
Colon and rectum	1.3 [1.3-1.4]
Gall bladder	1.3 [1.4-1.4]
Breast: postmenopausal	1.1 [1.1-1.2]
Ovary	1.1 [1.1-1.2]
Thyroid	1.1 [1.0-1.1]

Source: IARC, 2016

The association between BMI and endometrial cancer, especially type 1, showed a strong dose-response relationship—the higher the BMI, the stronger the association. For overweight women, the relative risk was 1.5; for women with class 1 obesity, RR was 2.5; for class 2 obesity, RR 4.5; for class 3, RR 7.1. For epithelial ovarian cancer, the association was modest (RR 1.1).

The IARC found numerous studies showing a positive association between weight and waist circumference in adult women and their risk of postmenopausal breast cancer, particularly for estrogen-receptor positive cancers. No similar risk appeared among premenopausal women, though the data were inconsistent.

Duration of Overweight/Obese

A recent study potentially adds more detail to the type of association between body weight and cancer risks.² In a longitudinal observational study, researchers used data from the Women’s Health Initiative trial of postmenopausal women. They selected a cohort of nearly 74,000 women with a mean follow-up of 12.6 years, during which 6,300 cancers were diagnosed. Thirty percent of the women were ‘ever’ overweight and had been so for an average of 30 years. Thirty percent were ‘ever’ obese and had been so for an average of 20 years.

In this study, the overall increased risk for endometrial cancer was 17%, followed by kidney cancer (16%). The increased risk for breast cancer was 5%. However, this particular study did not reveal significant associations with rectal, liver, gallbladder, pancreatic, ovarian, or thyroid cancers.

When the researchers looked at how excess weight affected risk over time, they found a dose-response relationship. For every 10 years of a woman being obese, the risk of being diagnosed with endometrial cancer rose 23%. For the same time increments, the hazard ratio for breast cancer rose 7%. Add to duration the degree of overweight, and the association increased even further. At highest BMI category, the risk for endometrial cancer increased 37% each decade.

What plausible mechanisms?

Current thinking about the mechanisms contributing to a body weight/cancer link echo those from two notable review papers.[3]^,[4] These reviewers said evidence points to the metabolic and endocrine abnormalities of obesity itself. These include “alterations in sex hormone metabolism, insulin and insulin-like growth factor signaling, and adipokines or inflammatory pathways.”¹ Evidence is strong for the role of sex hormones—e.g., adiposity promotes estrogen formation and synthesis—and for the role of chronic inflammation.

Hormone/binding globulin	Obese vs. normal weight women
Insulin	Increased levels with obesity
Insulin-like growth factor1 (IGF)	Non linear but peak levels w/ BMI 24-27
Free IGF1	Increased levels with obesity
IGF-binding protein1	Decreased levels with obesity
IGFBP2	Increased levels with obesity or no effect
Sex-hormone-binding globulin	Decreased levels with obesity
Total and free estradiol	Increased levels with obesity in postmenopausal women (not in premenstrual women)
Total testosterone	Increased levels in premenopausal women with PCOS
Free testosterone	Increased levels with obesity

Source: Calle EE, Kaaks R. Nat Rev Cancer 2004

Can weight loss help reduce cancer risk?

IARC researchers conclude that an “absence of body fatness lowers the risk of most cancers.” Counsel women to keep adiposity at normal weight levels. However, many women, young and old, are already at levels that may put them at increased risk for some cancers. Can losing some of their weight help reduce their risk?

There is some suggestion that intentional weight loss could be effective in minimizing cancer risks. Studies of intentional weight loss in animals show a cancer-preventive effect. Laboratory-oriented studies of the changes in metabolic and hormonal mechanisms accompanying weight loss are also suggestive.

The evidence from humans is thin, largely because the studies are observational or small, rather than because some evidence points another way. A review of studies of patients who have undergone bariatric surgery suggest a positive effect on oncologic risk and mortality, with the formerly obese women having a 0.68 relative risk of cancer when compared with obese women who did not undergo the surgery.[5] The reduction in risk was most notable for cancer of the breast and endometrium. The studies examining this question remain limited and of insufficient quality, but reducing excess adiposity remains good advice on other health measures. We may just find out one day that weight reduction has an added bonus advantage when it comes to cancer reduction.

—Submitted by Deborah Kowal, MA,PA, executive editor of Contraceptive Technology

[1] Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer — viewpoint of the IARC Working Group. N Engl J Med 375;8 nejm.org August 25, 2016

[2] Melina Arnold , Luohua Jiang, Marcia L. Stefanick, et al. Duration of adulthood overweight, obesity, and cancer risk in the Women’s Health Initiative: a longitudinal study from the United States. August 16, 2016 http://dx.doi.org/10.1371/journal.pmed.1002081

[3] Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4: 579-91.

[4] Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer 2015; 15: 484-98.

[5] Tee MC, Cao Y, Warnock GL, Hu FB, Chavarro JE. Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis. Surg Endosc 2013; 27: 4449-56.