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Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000-CT genotype (odds ratio [OR] = 0.15; p < 0.001) and the rs2228000-TT genotype (OR = 0.11; p < 0.001) compared to the reference genotype. Haplotype analysis within XPC revealed the rs2228001-A + G1475A-G + G2061A-A + rs2228000-T + rs3731062-C haplotype (OR = 0.26; p < 0.05) was associated with a significantly decreased disease risk. The haplotype analysis within the Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. What's new? Frequent mutation of the nucleotide excision repair (NER) system in both malignant melanoma and the inherited skin disease Xeroderma pigmentosum (XP) has led to speculation about whether XP may influence melanoma risk. Here, haplotype analysis of seven XP genes (XPA-XPG) in a Polish population uncovered a significant association between an XPC haplotype and decreased risk of malignant melanoma. Modest associations were also found for two XPD haplotypes. The findings contribute to the growing body of evidence that has implicated XPC and XPD polymorphisms as factors in melanoma susceptibility.

Background Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival has not been evaluated. Methods We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry. Results The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (

Background : There is continuing interest in identifying low-penetrance genes which are associated with an increased susceptibility to common types of cancer, including malignant melanoma. Methods : We sought to examine the association between four VDR common variants (rs1544410, rs731236, rs10735810, rs4516035) and the risk of melanoma in the Polish population. We also determined the prevalence of compound carriers of VDR and known MM genetic risk factors MC1R and CDKN2A (A148T) variants. We examined 763 unselected melanoma cases, 763 healthy adults matched for sex and age with the melanoma cases and 777 newborns. Results : None of the VDR variants alone or as compound carriers of two or more of the VDR genotypes were associated with MM risk. There were no major differences between the prevalences of the examined variants among patients with MM on UV-exposed and UV-non exposed skin areas, as well as among early-onset and late-onset cases. We found no association between VDR and MC1R or between VDR and CDKN2A common variants. A statistically significant over-representation of one VDR haplotype: rs731236_A+rs1544410_T (OR=3.2, p =0.02) was detected. Linkage disequilibrium of rs1544410 and rs731236 was confirmed. Conclusion : To answer the question, whether VDR can be regarded as melanoma susceptibility gene, additional, large multi-center association studies have to be performed.

The correct name of the ninth author is: Piotr Waloszczyk. The correct affiliation for this author is: Independent Laboratory of Pathology, Zdunomed, Szczecin, Poland.

Selenium deficiency has been suggested by several studies to be associated with cancer risk. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 86 cases of lung cancer, 87 cases of laryngeal cancer and an equal number of healthy controls. We studied the serum level of selenium and genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15) and the odds of being diagnosed with lung or laryngeal cancer. Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.7 µg/l for their matched controls (p 80 µg/l) was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.24 (95% CI 0.10 to 0.59; p = 0.002) for laryngeal cancer. In four selenoproteins studied here we found a modest associations of genetic variants in GPX1 and GPX4 with lung and TXNRD2 with laryngeal cancer risk. We analyzed iron (Fe) level in serum of 77 lung cancer patients and 77 matched controls. We did not find difference in mean Fe level between cases and controls (1053.05 µg/l and 1059.39 µg/l). However, we found that Fe level in the lowest and highest quartiles was associated with a significant lung risk enhancement when compared to a serum Fe level in the middle quartiles (OR 0.3, p 0.02). We also observed that the relationship between the level of Fe and Se could be an important factor for lung cancer risk.

Selenium deficiency has been suggested by several studies to be associated with cancer risk. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 86 cases of lung cancer, 87 cases of laryngeal cancer and an equal number of healthy controls. We studied the serum level of selenium and genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15) and the odds of being diagnosed with lung or laryngeal cancer. Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.7 µg/l for their matched controls (p 80 µg/l) was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.24 (95% CI 0.10 to 0.59; p = 0.002) for laryngeal cancer. In four selenoproteins studied here we found a modest associations of genetic variants in GPX1 and GPX4 with lung and TXNRD2 with laryngeal cancer risk. In this region of endemic low selenium level, there is a strong inverse association between the level of serum selenium and the risks of lung and laryngeal cancer.