Dataset Information

ASIP genetic variants and the number of non-melanoma skin cancers.

ABSTRACT: Patients with primary non-melanoma skin cancers (NMSCs) tend to develop these cancers at multiple independent sites. We examined the genetic factors in the development of multiple NMSCs among Caucasian women with 28 years of follow-up. We initially evaluated 19 SNPs in nine pigmentation genes with the number of NMSCs in 492 cases and 619 controls without a history of NMSC. We found nominal significant associations between two ASIP gene-related SNPs, rs1885120 and rs910873, and an ASIP haplotype (AH) (rs4911414 allele T and rs1015362 allele G) and an increased number of NMSCs, with p-values of 0.008, 0.01, and 0.01, respectively. We further evaluated these two SNPs and AH haplotype in three data sets. In a joint analysis with 1,507 cases and 4,335 controls, AH haplotype was independently associated with the number of NMSCs with odds ratio (OR) (95% confidence interval (CI)) of 1.45(1.25-1.68) (p-value = 6.2E-07). The AH haplotype was associated with an increased risk of developing one NMSC (OR 1.32; 95% CI, 1.07-1.63). The OR increased to 1.45(1.18-1.78) for those with 2-4 NMSCs and 1.84(1.34-2.53) for those with at least five. The findings suggest that ASIP locus is associated with the number of NMSCs.

SUBMITTER: Lin W

PROVIDER: S-EPMC3042546 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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ASIP genetic variants and the number of non-melanoma skin cancers.

Lin Wen W Qureshi Abrar A AA Kraft Peter P Nan Hongmei H Guo Qun Q Hu Frank B FB Jensen Majken K MK Han Jiali J

Cancer causes & control : CCC 20110109 3

Patients with primary non-melanoma skin cancers (NMSCs) tend to develop these cancers at multiple independent sites. We examined the genetic factors in the development of multiple NMSCs among Caucasian women with 28 years of follow-up. We initially evaluated 19 SNPs in nine pigmentation genes with the number of NMSCs in 492 cases and 619 controls without a history of NMSC. We found nominal significant associations between two ASIP gene-related SNPs, rs1885120 and rs910873, and an ASIP haplotype ...[more]

PMID: 21221757

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Project description:BackgroundThe Grainyhead-like (GRHL) transcription factors have been linked to many different types of cancer. However, no previous study has attempted to investigate potential correlations in expression of different GRHL genes in this context. Furthermore, there is very little information concerning damaging mutations and/or single nucleotide polymorphisms in GRHL genes that may be linked to cancer.MethodsDNA and RNA were extracted from human non-melanoma skin cancers (NMSC) and adjacent normal tissues (n = 33 pairs of samples). The expression of GRHL genes was measured by quantitative real time PCR. Regulation of GRHL expression by miRNA was studied using cell transfection methods and dual-luciferase reporter system. Targeted deep sequencing of GRHL genes in tumor samples and control tissues were employed to search for mutations and single nucleotide polymorphisms. Single marker rs141193530 was genotyped with pyrosequencing in additional NMSC replication cohort (n = 176). Appropriate statistical and bioinformatic methods were used to analyze and interpret results.ResultsWe discovered that the expression of two genes - GRHL1 and GRHL3 - is reduced in a coordinated manner in tumor samples, in comparison to the control healthy skin samples obtained from the same individuals. It is possible that both GRHL1 and GRHL3 are regulated, at least to some extent, by different strands of the same oncogenic microRNA - miR-21, what would at least partially explain observed correlation. No de novo mutations in the GRHL genes were detected in the examined tumor samples. However, some single nucleotide polymorphisms in the GRHL genes occur at significantly altered frequencies in the examined group of NMSC patients.ConclusionsNon-melanoma skin cancer growth is accompanied by coordinated reduced expression of epidermal differentiation genes: GRHL1 and GRHL3, which may be regulated by miR-21-3p and -5p, respectively. Some potentially damaging single nucleotide polymorphisms in GRHL genes occur with altered frequencies in NMSC patients, and they may in particular impair the expression of GRHL3 gene or functioning of encoded protein. The presence of these polymorphisms may indicate an increased risk of NMSC development in affected people.

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ASIP genetic variants and the number of non-melanoma skin cancers.

Publications

ASIP genetic variants and the number of non-melanoma skin cancers.

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