We liked that this study was so large, and that researchers replicated their results in three subsequent studies, so the variants found showed a solid link to colon cancer.

About 30 percent of colorectal cancer can be traced to inherited susceptibility. But the sort of high-penetrance genetic mutations that almost always result in colorectal cancer account for less than 5 percent of cases. Researchers surmised that the missing part of genetic risk came from relatively common variants that have minor effects on their own but together can instigate colorectal cancer.

They looked for likely suspects in variants found in the area of the SMAD7 gene, involved in cell signaling. Researchers knew SMAD7 was a good place to look because previous studies showed manipulating how the gene was expressed led to colorectal cancer progression. (SMAD proteins are homologs or equivalents of the fruit fly protein called "mothers against decapentaplegic," or MAD. It got this odd name after fruit fly researchers found that a mutation in the gene in the mother repressed the gene called decapentaplegic in the embryo. They dubbed it "mothers against" in reference to organizations such as Mothers Against Drunk Driving.)

Researchers then conducted a massive multistage hunt -- a genome-wide association study of 940 white men and women with familial colorectal cancer and a control population of 965 healthy individuals, and found three likely variants, which they then tested again in three other studies of similar size and population.

More: To read an abstract of this paper on PubMed, a medical database, click here.