Browsing by Author "Brewer, Jerry D."

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    Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer
    (Oxford University Press, 2021-08-30) Besson, Caroline; Moore, Amy; Wu, Wenting; Vajdic, Claire M.; de Sanjose, Silvia; Camp, Nicola J.; Smedby, Karin E.; Shanafelt, Tait D.; Morton, Lindsay M.; Brewer, Jerry D.; Zablotska, Lydia; Engels, Eric A.; Cerhan, James R.; Slager, Susan L.; Han, Jiali; Berndt, Sonja I.; Medical and Molecular Genetics, School of Medicine
    Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
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    Systematic Review and Meta-Analysis of Local Recurrence Rates of Head and Neck Cutaneous Melanomas after Wide Local Excision, Mohs Micrographic Surgery, or Staged Excision
    (Science Direct, 2021-09-01) Bittar, Peter G.; Bittar, Julie M.; Etzkorn, Jeremy R.; Brewer, Jerry D.; Aizman, Leora; Shin, Thuzar M.; Sobanko, Joseph F.; Higgins, Harold W.; Giordano, Cerrene N.; Cohen, Justine V.; Pride, Renee; Wan, Marilyn T.; Leitenberger, Justin J.; Bar, Anna A.; Aasi, Sumaira; Bordeaux, Jeremy S.; Miller, Christopher J.; Dermatology, School of Medicine
    Background Prospective trials have not compared local recurrence rates for different excision techniques for cutaneous melanomas on the head and neck. Objective To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. Methods A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies and randomized controlled trials that reported local recurrence rates after surgery of cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. Results Among one-hundred manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE; 34.5% (4,826) by MMS; and 14.5% (2,034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95%CI, 0.1%-1.4%); followed by staged excision (1.8%; 95%CI, 0.1%-2.9%) and WLE (7.8%; 95%CI, 6.4%-9.3%). Limitations Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. Conclusion Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.