A novel gene-environment interaction involved in endometriosis

To establish a well-defined cohort for genetic epidemiology studies of endometriosis and conduct a pilot study to confirm validity using existing data associated with endometriosis.

Between January and May 2010, a nested cohort within a population-based biobank was established in Marshfield, Wisconsin, USA. The inclusion criteria were women who had laparoscopy or hysterectomy. Fifty-one pleiotropic genetic polymorphisms and other established risk factors, such as smoking status and body mass index, were compared between endometriosis cases and controls.

From the existing biobank, 796 cases and 501 controls were identified, and 259 women with endometriosis were enrolled specifically for the nested cohort within this biobank. A single nucleotide polymorphism in the MMP1 gene significantly differed between cases and controls only when stratified by smoking status. Minor allele frequency was higher in control women who smoked than in women with endometriosis who smoked (55.5% versus 45.5%, χ(2)=8.2, P=0.017); the inverse relationship was found in non-smoker control women.

Women with endometriosis were successfully recruited to participate in a general biobank, and a novel gene-environment interaction was identified. The findings suggest that important potential genetic associations may be missed if gene-environment interactions with known epidemiologic risk factors are not considered.