It has long been known that being over­weight or obese is asso­ci­ated with an increased risk for many types of can­cer, includ­ing post­menopausal breast, endome­trial, col­orec­tal, esophageal, gall­blad­der, kid­ney, pan­cre­atic, and thy­roid can­cer. In 2002, the Inter­na­tional Agency for Research on Can­cer esti­mated that obe­sity con­tributed to more than one-​​third of endome­trial and esophageal can­cer and one-​​quarter of kid­ney can­cer cases.

Being over­weight or obese also raises the risk of dying of can­cer. In 2003, Calle, Rodriguez, Walker-​​Thurmond, and Thun esti­mated that 14% of all can­cer deaths in men and 20% in women were caused by excess weight.

The ques­tions is, why? What is the process through which excess weight increases can­cer risk? All of the research being done now is rooted in the recog­ni­tion that adi­pose (fat stor­age) tis­sues are highly meta­bol­i­cally active tis­sues that pro­duce an array of hor­mones, growth fac­tors, and sig­nal­ing molecules.

Accord­ing to the edi­tors of a spe­cial edi­tion of the NCI Can­cer Bul­letin focus­ing on this topic, one path­way from obe­sity to can­cer involves the hor­mone estro­gen, which fuels a large num­ber of breast and endome­trial can­cers (“Obe­sity and can­cer research,” 2011). Cir­cu­lat­ing estro­gen nor­mally drops dras­ti­cally in post­menopausal women as the ovaries stop pro­duc­ing the hor­mone. In obese women, how­ever, their body fat becomes an estrogen-​​producing machine, accord­ing the edi­tors of the spe­cial issue. The estro­gen cre­ated by the excess fat fuels can­cer cells that express the estro­gen receptor.

Another fac­tor is insulin, the hor­mone that tells cells in the body to absorb glu­cose from the blood­stream. Obe­sity often accom­pa­nies meta­bolic syn­drome and type II dia­betes, where the body’s cells stop respond­ing to insulin, caus­ing a buildup of insulin in the blood, which in turn stim­u­lates the body to pro­duce more insulin. In some can­cers, includ­ing breast, col­orec­tal, and pan­cre­atic can­cer, insulin appears to encour­age the body to begin cell divi­sion, which makes the can­cer grow faster. One dia­betes drug, met­formin, which low­ers the lev­els of blood glu­cose, has shown some anti­cancer activ­ity. Cur­rently, sev­eral clin­i­cal tri­als are under way to test the addi­tion of met­formin to stan­dard can­cer treatments.

Sev­eral other mol­e­cules are also being stud­ied to deter­mine whether they con­tribute to the rela­tion­ship between obe­sity and can­cer. Inter­leukins are a part of the body’s inflam­ma­tory response, which is often over­stim­u­lated in peo­ple who are obese. Cytokines are sig­nal­ing mol­e­cules that are increased with weight gain.

Research is cur­rently under way to inves­ti­gate mol­e­c­u­lar path­ways that link obe­sity and can­cer risk in humans. One is study­ing estro­gens and estro­gen metabo­lites, and another is study­ing inflam­ma­tion mark­ers to see which mol­e­c­u­lar mech­a­nisms are most related to can­cer. Other researchers are look­ing at genetic vari­ants that might be asso­ci­ated with obe­sity and can­cer risk, specif­i­cally which genetic vari­ants are asso­ci­ated with colon polyp formation.

This research may one day lead to tar­geted can­cer pre­ven­tion pro­grams and treat­ments for over­weight and obese peo­ple, based on an under­stand­ing of the mech­a­nisms dri­ving can­cer pro­gres­sion. For now, can­cer experts agree that the research sup­ports adopt­ing a healthy lifestyle that pro­motes weight control.

• Calle, E.E., Rodriguez, C., Walker-​​Thurmond, K., & Thun, M.J. (2003). Over­weight, obe­sity, and mor­tal­ity from can­cer in a prospec­tively stud­ied cohort of U.S. adults. New Eng­land Jour­nal of Med­i­cine, 348, 1625–1638. doi: 10.1056/NEJMoa021423
• Inter­na­tional Agency for Research on Can­cer. (2002). Weight con­trol and phys­i­cal activ­ity. Retrieved from http://​www​.iarc​.fr/​e​n​/​p​u​b​l​i​c​a​t​i​o​n​s​/​p​d​f​s​-​o​n​l​i​n​e​/​p​r​e​v​/​h​a​n​d​b​o​o​k​6​/index.php
• Obe­sity and Can­cer Research [Spe­cial issue]. (2011). National Can­cer Insti­tute Can­cer Bul­letin, 8(22). Retrieved from http://​www​.can​cer​.gov/​n​c​i​c​a​n​c​e​r​b​u​l​l​e​t​i​n​/​1​1​1511/page1