THE ASSOCIATION OF SEX-STRATIFIED MGMT DNA REPAIR SNPS IN MELANOMA RISK
Christopher Hughes1, Jenna Lilyquist1, Kirsten White1, Salina Torres1, Li Luo1, DeAnn Lazovich2, Marianne Berwick1.
1The University of New Mexico, Albuquerque, NM, 2University of Minnesota, Minneapolis, MN.
Cutaneous melanoma utilizes a complex and dynamic route to pathogenesis that is not entirely understood. Incidence rates over the past several decades have risen and fueled investigations to elucidate the causes of melanoma. Melanoma is the 6th most common cancer in the U.S. with an estimated 73,870 new cases and 9,940 deaths predicted in 2015. Males experience higher mortality and incidence rates than females, but little is known about the sex-dependent biological differences for risk. Genetic factors, including DNA repair genes, have been reported to play a role in melanomagenesis. The O6-methylguanine-DNA methyltransferase (MGMT) gene encodes an enzyme involved in DNA repair, and single nucleotide polymorphisms (SNPs) in this gene are implicated in melanoma risk and survival. We genotyped 893 melanoma cases and 766 control participants from the Minnesota Skin Health Study for 24 SNPs in MGMT. Males had an increase in risk for rs4750766 (p = 0.04, OR 1.45, 95% CI = 1.14 - 1.83) and a decrease in risk for rs7075505 (p = 0.002, OR 0.71, 95% CI = 0.05 - 0.98). There were no significant variants associated with melanoma risk in females. When controlling for multiple tests, the SNPs did not meet correction for false discovery; however, DNA repair variants in MGMT may still play a role in sex-dependent risk for melanoma. Although MGMT’s exact influence on melanomagenesis remains unknown, further investigation into the function of these SNPs could provide useful insight into sex-specific risk.