Genetic factors, obesity and cancer risk

4 October 2008

Previous epidemiological studies have shown an association between obesity and an increased risk of certain cancers, including breast and colorectal cancer, a link with significant public health implications. For example, men with high Body Mass Index (BMI) values have an increased risk of developing colorectal cancer [Caan BJ et al. (1998) Int J Obes Relat Metab Disord. 22(2):178-84]. A new paper in JAMA reports findings that link the adiponectin pathway in fat cells with a decreased risk of colorectalcancer. The hormone adiponectin is secreted by adipocytes (fat cells) and levels are inversely correlated with obesity; that is, levels tend to be lower in obese individuals.

Researchers looked at associations between adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk in two US study populations [Kaklamani VG et al. (2008) JAMA 300(13):1523-1531]. One study included 441 patients with colorectal cancer and 658 controls, whilst the other included 199 patients and 199 controls. They found that a single-nucleotide polymorphism (SNP) in the ADIPOQ gene (rs266729) was linked with a reduced risk of colorectal cancer. Individuals with a GG/GC genotype at this SNP had a 27% lower probability of developing colorectal cancer than those with a CC genotype.

The authors suggest that if replicated, these findings would suggest that the adiponectin pathway could be an important modifier of colorectal cancer risk, and that genotypic information from pathway genes might inform estimates of risk. They also report that several other SNPs from the same region could be associated with colorectal cancer risk.

Comment: The same research group reported earlier this year that different SNPs in the adiponectin gene were modifiers of breast cancer risk [Kaklamani VG et al. (2008) Cancer Res. 68(9):3178-84], suggesting in this latest paper that fine (higher resolution) mapping may be required to determine whether the key risk-associated SNPs are genuinely distinct for breast and colorectal cancer risk. However, the adiponectin pathway seems likely to play a role in influencing risk of cancer and represents one potential link with obesity.

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