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Study finds association between fat-cell hormone and cancer

6 October 2008
Appeared in BioNews 478

Writing in the Journal of the American Medical Association (JAMA), Dr Boris Pasche and team at the University of Alabama, Birmingham, US, report an association between variations in a fat-cell hormone gene, and colorectal cancer. The study profiled ten SNPs (single nucleotide polymorphisms) - point changes in DNA, pronounced 'snip' in 1,497 participants. One genetic variation in particular was significantly associated with a 27 per cent reduced risk of colorectal cancer.

In the study, focusing on two geographically-unrelated cohorts over a seven-year period, SNPs in both the gene for the hormone, adiponectin (ADIPOQ), and its receptor (ADIPOR1), were measured for their association with cancer. After adjustment for sex, age and ethnicity, one particular SNP in ADIPOQ remained significantly associated with a decreased colorectal cancer risk. Approximately 50 per cent of participants carried this gene version.

The genetic variant results in reduced production of adiponectin, a phenomenon also observed in obesity and type 2 diabetes. One role of adiponectin is to regulate fatty acid breakdown, so it is possible to envisage how reduced production might lead to obesity. How it might lead to colorectal cancer is less clear. One hypothesis is that in addition to elevated insulin levels (a feature of type 2 diabetes), low adiponectin correlates with increased levels of insulin-like growth factor (IGF). This protein drives cellular proliferation and inhibits of cell death, both important hallmarks of cancer. Epidemiological studies have previously suggested that family history is a risk factor associated with one-third of colon cancer cases worldwide.

From his work, Dr Pasche hopes that 'we can significantly improve the screening and early detection for this disease'. One disadvantage of relying on genetic screens is that many patients, if feeling healthy, might not consider them a necessity. However because the particular SNP identified is also associated with obesity and diabetes, both easily-identifiable conditions, affected patients might undertake genetic screening or, better still, colorectal screening more often.

Interestingly, the gene variant lies some 11,000 nucleotides upstream of the gene start site, within the gene's 'promoter' region. Whilst it is possible that a genetic change here might affect adiponectin levels, the chances are that the 'functionally-significant' SNPs are elsewhere, and that the SNP identified here is merely inherited, faithfully, alongside these.

'Is this the (genetic) snip that is the cause of the disease? Most likely not,' conceded Dr Pasche. 'It just gives us a region on the gene where we think the association to colorectal cancer risk stems from'.

Colon Cancer Link To Obesity Uncovered
ScienceDaily |  1 October 2008
Gene for Fat Cell Hormone Impacts Colorectal Cancer Risk
Medpage Today |  30 September 2008
Genetic link found to colon cancer in study
Reuters |  30 September 2008
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