**Author details**

are at higher risk of tobacco and alcohol-related cancers independently from their initial

What is lacking is a study of cancer cases and the risk of cleft palate in their family members. Such studies are limited by the fact that the genetic defect is still a rare event, and the number of cancer cases necessary to address the problem would be extremely large. A study conducted on family members of cancer patients (Taioli et al. [95]) involved an epidemiological questionnaire including family history of cancer and congenital oral cleft malformations that was administered to 168 cancer survivors and a population-based sample of 170 healthy subjects. In the control group, 1.2% reported a family member with CL/P; among cancer survivors, the figure was 4.2% (odds ratio: 3.7; 95% confidence interval: 0.75–17.8; *p* = .07). Among cancer survivors with a family member with CL/P, there was an apparent excess of testicular cancer and melanoma in comparison with the cancer survivors with no family history of CL/P. These preliminary results suggest a common etiologic background for cancer and CL/P.

Taken all together, the data suggest that there are shared environmental and genetic factors in

OFCs are the most common craniofacial anomalies, and one of the most common congenital anomalies worldwide. OFCs have historically been grouped as CL/P or CPO. However, existing evidence suggests that separate etiologies may exist for cleft lip alone versus cleft lip with palate. CL/P and CPO are classified as syndromic or nonsyndromic; nonsyndromic cases are

Both genetic and environmental factors have been implicated in the etiology of OFC. The genes underlying a number of known syndromes associated with OFC have been identified. Furthermore, environmental factors such as alcohol and tobacco have been shown to modu-

Although nonsyndromic OFCs are not traditionally the subject of genetic analysis, a number of genomic association studies have evaluated the link between genetic variants and nonsyndromic OFC. Examples of genes that have been examined in such studies include those that code for growth factors, transcription factors, and nutrient metabolism proteins. In addition to genetic factors, studies have recently begun to explore the role of epigenetic modifications

A number of environmental and maternal factors that influence the risk of having a child with OFC are well-described. In particular, family history, maternal drug use, nutrition, and exog-

Several studies have shown a higher incidence of cancer amongst patients with CL/P and their families. Additionally, studies have begun to identify higher rates of CL/P in the families of patients with cancer, although less is known about this. Combined, these suggest that CL/P

enous exposures demonstrate strong links with development of OFC in the child.

and cancer may be mediated by shared environmental and genetic etiologies.

families that predispose to both cleft palate and cancer.

further subclassified as multiple or isolated.

in palatal ontogeny and etiology of OFC.

late the risk of OFC conferred by certain genetic factors.

malformation.

14 Designing Strategies for Cleft Lip and Palate Care

**9. Conclusion**

Mairaj K. Ahmed1 \*, Anthony H. Bui<sup>2</sup> and Emanuela Taioli<sup>3</sup>

\*Address all correspondence to: mairaj.ahmed@mountsinai.org

1 Cleft/Craniofacial Center, Icahn School of Medicine at Mount Sinai, NY, NY, USA

2 Icahn School of Medicine at Mount Sinai, NY, NY, USA

3 Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, NY, NY, USA
