DLX1 and MMP3 contribute to oral clefts with and without positive family history of cancer.

OBJECTIVE:It has been suggested that oral clefts and cancer share a common genetic background. This study aimed to investigate the epidemiological and molecular association between oral clefts and cancer. METHODS:One hundred forty-eight nuclear families with oral clefts and 162 subjects with no birth defect were recruited. Data on self-reported family history of cancer among first, second, and third degree relatives of each patient were collected via a structured questionnaire. We also investigated the association between polymorphisms in the genes AXIN2, BMP2, BMP4, BMP7, DLX1, DLX2, and MMP3 and oral cleft with and without history of cancer. Markers in these genes were genotyped using real time PCR. Chi-square and t-test were used to assess the differences about self-reported family history of cancer between oral cleft and non-cleft individuals. The transmission disequilibrium test (TDT) was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. RESULTS:Families with oral clefts had an increased risk of having a family history of cancer (p=0.01; odds ratio=1.79; 95% confidence interval, 1.07-1.87). TDT results showed an association between DLX1 and cleft lip and palate, in which the A allele was undertransmited (p=0.022). For MMP3, G was undertransmited among affected progeny (p=0.019) in cleft palate subgroup. CONCLUSION:Oral clefts were associated with positive self-reported family history of cancer and with variants in DLX1 and MMP3. The association between oral clefts and cancer raises interesting possibilities to identify risk markers for cancer.

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