The obesity gene and colorectal cancer risk: A population study in Northern Italy

Background: Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity. Aims: To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population. Patients and methods: 1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F = 197/144, mean age = 65.17 ± 11.16 years), colorectal adenoma (385 pts., M/F = 247/138, mean age = 62.49 ± 13.01 years), healthy controls (311 pts., M/F = 150/161, mean age = 57.31 ± 13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR. Results: The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR = 1.106; CI 95% = 0.788-1.550; p = 0.561) or colorectal adenomas (OR = 0.830; CI 95% = 0.602-1.144; p = 0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI. Conclusion: The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.