The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
Most known cancer syndromes confer an increased risk of more than one tumour types, and families with more than one colorectal cancer often segregate other cancers as well. The aim of this study was to examine if there is a general increased risk of other cancers in colorectal cancer families, which are defined as having two or more cases of colorectal cancer in close relatives.
The study used a detailed family history of cancer diagnoses in a cohort of more than 3,000 consecutive colorectal cancer cases. A comparison was made between families with sporadic and those with familial colorectal cancer cases. Detailed morphology data were used to find further support for putative syndromes.
There were significantly more non-colorectal cancers in the family history of the familial CRC cases (p