Dataset Information

Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.

ABSTRACT: Genetic factors play an important role in cutaneous squamous cell carcinoma risk. Genome-wide association studies have identified 21 single nucleotide polymorphisms associated with cutaneous squamous cell carcinoma risk. Yet no studies have attempted to quantify the contribution of heritability to cutaneous squamous cell carcinoma risk by calculating the population attributable risk using a combination of all discovered genetic variants. Using an additive multi-locus linear logistic model, we determined the cumulative association of these 21 genetic regions to cutaneous squamous cell carcinoma population attributable risk. We computed a multi-locus population attributable risk of 62%, suggesting that if the effects of all the risk alleles were removed from a population, the cutaneous squamous cell carcinoma risk would drop by 62%. Using stratified analysis, we also examined the impact of sex on polygenic risk score, and found that men have an increased relative risk throughout the spectrum of the polygenic risk score. Quantifying the impact of genetic predisposition on the proportion of cancer cases can guide future research decisions and public health policy planning.

SUBMITTER: Sordillo JE

PROVIDER: S-EPMC6019610 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.

Sordillo Joanne E JE Kraft Peter P Wu Ann Chen AC Asgari Maryam M MM

The Journal of investigative dermatology 20180213 7

Genetic factors play an important role in cutaneous squamous cell carcinoma risk. Genome-wide association studies have identified 21 single nucleotide polymorphisms associated with cutaneous squamous cell carcinoma risk. Yet no studies have attempted to quantify the contribution of heritability to cutaneous squamous cell carcinoma risk by calculating the population attributable risk using a combination of all discovered genetic variants. Using an additive multi-locus linear logistic model, we de ...[more]

PMID: 29452120

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Project description:Importance:No study, to our knowledge, has prospectively investigated a dose-response association between lifetime indoor tanning and risk of cutaneous squamous cell carcinoma (SCC). Objective:To investigate the dose-response association between lifetime indoor tanning and SCC risk, the association between duration of use and age at initiation with SCC risk, and the association between age at initiation and age at diagnosis. Design, Setting, and Participants:This cohort study included data from women born from 1927 to 1963 from the Norwegian Women and Cancer study, established in 1991 with follow-up through December 31, 2015. Baseline questionnaires were issued to participants from 1991 to 2007, with follow-up questionnaires given every 5 to 7 years. Data analysis was performed from January 2, 2018, to March 2, 2019. Exposures:Participants reported pigmentation factors. Sunburns, sunbathing vacations, and indoor tanning were reported for childhood, adolescence, and adulthood. Main Outcomes and Measures:Information on all cancer diagnoses and dates of emigration or death were obtained through linkage to the Cancer Registry of Norway, using the unique personal identification number of Norwegian citizens. Results:A total of 159?419 women (mean [SD] age at inclusion, 49.9 [8.3] years) were included in the study. During follow-up (mean [SD], 16.5 [6.4] years), 597 women were diagnosed with SCC. Risk of SCC increased with increasing cumulative number of indoor tanning sessions. The adjusted hazard ratio (HR) for highest use vs never use was 1.83 (95% CI, 1.38-2.42; P?<?.001 for trend). A significantly higher risk of SCC was found among women with 10 years or less of use (HR, 1.41; 95% CI, 1.08-1.85) and more than 10 years of use (HR,?1.43; 95% CI, 1.16-1.76) and among women with age at initiation of 30 years or older (HR,?1.36; 95% CI, 1.11-1.67) and younger than 30 years (HR,?1.51; 95% CI, 1.18-1.92) vs never users. No significant association was found between age at initiation and age at diagnosis (estimated regression coefficient, -0.09 [95% CI, -1.11 to 0.94] for age at initiation of ?30 years and -0.02 [95% CI, -1.27 to 1.22] for <30 years vs never use). Conclusion and Relevance:The findings provide supporting evidence that there is a dose-response association between indoor tanning and SCC risk among women. The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation. These results support development of policies that regulate indoor tanning.

Dataset Information

Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.

Publications

Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.

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