HEALTH NEWS

Study Title:

Colon Cancer and Obesity Linked

Study Abstract

Context Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date.

Objective To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk.

Design, Setting, and Patients Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity.

Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequency among cases and controls.

Results In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99).

Conclusion The SNP rs266729, which tags the 5' flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.

From press release:

A new study reveals the first-ever genetic link between obesity and colon cancer risk, a finding that could lead to greater accuracy in testing for the disease, said a researcher at the University of Alabama at Birmingham (UAB).

The discovery also may improve efforts to ward off colon cancer with obesity-fighting activities like exercise, weight loss and healthy eating.

"Our hope is that we can significantly improve the screening and early detection for this disease, and open new avenues for better understanding the genetic and lifestyle factors that influence colon cancer risk," said Boris Pasche, M.D., Ph.D., director of the division of hematology and oncology at the UAB Comprehensive Cancer Center and lead author of the JAMA study.

The research focuses on a gene called ADIPOQ that results in the formation of a fat hormone called adiponectin. It shows those who inherit a common genetic variant of ADIPOQ carry up to 30 percent reduced risk of colon cancer compared to others.

In other words, Pasche said, those identified without the gene variant or those who have unhealthy blood levels of adiponectin may benefit from early colorectal testing. Additional studies are needed to confirm whether those without the variant benefit from cancer-prevention lifestyle changes such as diet and exercise.

Colon cancer is the third-leading cancer killer of Americans. This year 149,000 people will be diagnosed with colon cancer and 50,000 will die from the disease, according to estimates from the American Cancer Society.

One-third of people with colon cancer have a clear family history of the disease, and now scientists are homing in on the exact DNA sequences or mutations within the ADIPOQ gene that influence colon cancer risk, Pasche said.

It has already been proven that obesity is influenced by genetics, and colon cancer is influenced by genetics. The JAMA study is the first to make a three-way scientific connection between genetic variation, obesity and colon cancer risk.

Other research has shown adiponectin is associated with diabetes, insulin resistance, cardiovascular disease and with influencing cell growth in colonic tissues. Exactly how adiponectin or its genes directly impact tumor growth is still unknown, but those cell pathways are being widely studied, Pasche said.

A separate gene variant in ADIPOQ is a known modifier for breast-cancer risk, according a recent study in the journal Cancer Research that was co-authored by Pasche.

The new JAMA study was performed with blood samples taken from 1,497 participants, including healthy volunteers and colon cancer patients. It includes both sexes and a mix of age, race and ethnicity.

Study Information

Virginia G. Kaklamani; Kari B. Wisinski; Maureen Sadim; Cassandra Gulden; Albert Do; Kenneth Offit; John A. Baron; Habibul Ahsan; Christos Mantzoros; Boris Pasche.
Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk
JAMA
2008 October
Cancer Genetics Program, Division of Hematology and Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. .