Polymorphisms in base excision DNA repair genes and association with melanoma risk in a pilot study on Central-South Italian population.

Base excision repair plays a key role in the removing of DNA damage from exposure to endogenous and exogenous carcinogens. The BER pathway removes alterations of a single oxidized, reduced or methylated base. Recently some studies have explored the association between risk for cutaneous melanoma and non-synonymous single-nucleotide polymorphisms (nsSNPs) in DNA-repair genes, although with contradictory results. We hypothesized that common nsSNPs of BER genes, specifically ADPRT rs1136410, XRCC1 rs25487, rs25489, rs1799782, APEX1 rs1130409, OGG1 rs1052133, LIG3 rs3136025 and MUTYH rs3219466, may contribute to risk of melanoma. The aim of this study is to investigate whether or not a correlation between these nsSNPs and melanoma risk and/or aggressiveness is present. 167 melanoma patients and 186 healthy control subjects were analysed. By multivariate statistical analysis no association was found between nsSNP and melanoma aggressiveness, while only the two XRCC1 (rs25487 and rs25489) nsSNPs showed a strong correlation (p<0.001) with melanoma risk. To our knowledge this is the first study reporting an association between BER nsSNPs and melanoma risk in Central-South Italian individuals. Our findings, if confirmed in larger population studies, will allow the inclusion of these XRCC1 nsSNPs in a screening panel for those individuals at higher risk for melanoma.

Common genetic variants of MUTYH are not associated with cutaneous malignant melanoma: application of molecular screening by means of high-resolution melting technique in a pilot case-control study.

MUTYH glycosylase recognizes the 8-oxoG:A mismatch and is able to excise the adenine base using proofreading mechanisms. Some papers have reported a strong association between cancer development or aggressiveness and MUTYH gene mutations. The aim of this study was to find a possible association between the most frequent MUTYH mutations and melanoma in the context of a case-control pilot study. One hundred ninety-five melanoma patients and 195 healthy controls were matched for sex and age. Clinical and laboratory data were collected in a specific database and all individuals were analyzed for MUTYH mutations by high-resolution melting and direct sequencing techniques. Men and women had significantly different distributions of tumor sites and phototypes. No significant associations were observed between the Y165C, G382D and V479F MUTYH mutations and risk of melanoma development or aggressiveness. Our preliminary findings therefore do not confirm a role for MUTYH gene mutations in the melanoma risk. Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.

Insulin-like growth factor I (CA) repeats are associated with higher melanoma's Breslow index but not associated with the presence of the melanoma. A pilot study.

BACKGROUND: IGF-I-(CA) repeats have been previously analysed in few types of cancer and the results, although discordant in different studies, showed possible associations between cancer and IGF-I(CA)(19) repeats. Aim of this pilot study was to detect a possible association between some of the IGF-I(CA) repeats and the presence of malignant melanoma and its Breslow index. METHODS: Two hundred patients affected with cutaneous malignant melanoma and 100 control healthy subjects were analysed for IGF-I(CA) repeats by fragment analysis sequencing and, partially, confirmed by direct sequencing. RESULTS: A significant association of IGF-I(CA)(19) repeats was observed with melanoma higher Breslow indices (P<0.001), while no association between melanoma patients and the different genotypes of IGF-I(CA) was found. The above mentioned association was confirmed after Bonferroni's correction for multiple comparisons and also by logistic regression analysis adjusted for age, sex and BMI variables. A slight, significant difference (P=0.03) was observed for serum IGF-I values in IGF-I(CA)(19)-positive or IGF-I(CA)(19)-negative subjects. DISCUSSION: The association observed for IGF-I(CA)(19) and malignant melanoma is in keeping with similar results obtained in prostate or breast cancers, suggesting that this type of repeat may be directly or indirectly important in controlling cancer induction and its severity.