Germline mutations of the CDKN2A and CDK4 genes explain a significant proportion of familial melanoma. To date, there have been few published estimations of the prevalence of such mutations in sporadic melanoma patients. In this study, we investigated CDKN2A and CDK4 exon 2 for germline mutations in 125 consecutive cutaneous malignant melanoma patients recruited through the Latvian Oncological Center, using amplicon melting analysis and sequencing. No disease-related CDKN2A germline mutations were identified in any of the melanoma patients analysed but the previously described CDK4 mutation, Arg24His, was found in one patient with a family history of melanoma. CDKN2A polymorphisms were studied as putative low penetrance susceptibility genes. The proportion of cases with polymorphisms in this Latvian melanoma population was Ala148Thr (c.442G>A) (6%), 500 C/G (c.*29C>G) (18%), and 540 C/T (c.*69C>T) (20%); however, only the frequency of the Ala148Thr polymorphism was higher in melanoma patients than in 203 controls (6 versus 1%, P=0.03). Ala148Thr has also been reported in association with melanoma in a Polish series but not in an English series. We therefore examined the Ala148Thr carrier's haplotype in 10 Latvian and 39 Polish samples. No significant difference was seen between these populations and the predominant haplotype observed in English samples, giving no indication that the discrepancy could be explained by population differences in linkage disequilibrium. In summary, our results show that germline mutations at the CDKN2A locus are rare in sporadic melanoma in Latvia. The study does, however, provide some additional evidence for a role for the CDKN2A polymorphism Ala148Thr as a low penetrance susceptibility gene. The detected CDK4 exon 2 mutation was found in only the seventh family identified worldwide with a germline CDK4 mutation.

Traditionally in Latvia, most women request gynecological services for preventive and health promotion reasons or in the case of having a gynecological disease. So the overloaded general practitioners and the lack of involvement of gynecologists are one of the main obstacles to solve for implementing an organized screening program in Latvia. Moreover insufficient availability of quality-assured services and resources for cytology testing and other services of the program, and for monitoring and evaluating the whole program, must be considered in the implementation of a comprehensive screening plan.t

We have analysed 47 early-onset (< or =40 years) Latvian melanoma patients for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. We observed no disease-related mutations in CDKN2A, but one patient had a CDK4 R24H mutation and strong family history of melanoma. Haplotype analysis using microsatellite markers and single nucleotide polymorphisms showed that the Latvian haplotype is unique compared with that of other melanoma families with the R24H mutation. This finding supports the proposal that codon 24 is a mutational hotspot in the CDK4 gene.

To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, P<0.001). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, P<0.001) that of carriers of one variant (OR 1.98, 95% CI 1.26-3.11, P=0.003). After stratification according to the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.

The first objective of the study was to investigate medical staff's awareness, motivation, and readiness to take part in the CSP, with the ultimate aim of increasing the response rate to invitation letters and improving the effectiveness and screening coverage in Latvia. The second objective was to identify issues and problems preventing medical staff's involvement in implementing the CSP. The third objective was to provide recommendations to the CSP administrators on how to optimize cooperation of medical staff in implementing the screening program in Latvia. Ethical approval was granted for the study by Riga Stradiņš University Ethics Committee on January 3rd, 2011. The study population was certified GYNs and GPs currently practicing in the national and private healthcare systems in Latvia involved in carrying out the CSP. A questionnaire was designed containing multiple-choice questions in three areas: 1) the socio-demographic background of the medical professional and his or her daily activities in cervical cancer screening, 2) the medical professional's perception of cervical cancer screening and cervical cancer prevention, and 3) the medical professional's perception of the Latvian CPS model and assessment of his or her own screening-related knowledge. The questionnaires were distributed to GYNs during the general meeting of the Latvian Association of Gynecologists and Obstetricians in May 2011. GPs were randomly selected from a list of all registered Latvian GPs that have contracts with the National Health Service (NHS; Nacionālais veselības dienests). They were sent the questionnaire by mail or it was delivered to their mailboxes at the NHS premises with a prepaid return-addressed envelope. The data were analyzed using the χ² test independent samples,

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