Background Clinical whole exome sequencing was introduced in an Australian centre in 2017, as an alternative to Sanger sequencing. We aimed to identify predictors of cancer physicians’ somatic mutation test ordering behaviour. Methods A validated instrument assessed somatic mutation test ordering, genomic confidence, perceived utility of tumour molecular profiling, and percent of patients eligible for targeted therapy. A cash incentive was included in 189/244 questionnaires which were mailed to all Queensland cancer specialists in November 2018. Results 110 participated (response rate 45%); 54.7% oncologists, and the remainder were surgeons, haematologists and pulmonologists. Oncologists were more likely to respond (p = 0.008), and cash incentive improved the response rate (p < 0.001). 67/102 (65.7%) of physicians ordered ≥ 5 somatic mutation tests annually. Oncologists saw 86.75 unique patients monthly and ordered 2.33 somatic mutation tests (2.2%). An average of 51/110 (46.1%) reported having little/no genomic confidence. Logistic regression identified two significant predictors of somatic mutation test ordering: being an oncologist (OR 3.557, CI 1.338–9.456; p = 0.011) and having greater confidence in interpreting somatic results (OR 5.926, CI 2.230–15.74; p < 0.0001). Conclusions Consistent with previous studies, the majority of cancer physicians ordered somatic mutation tests. However, the percentage of patients on whom tests were ordered was low. Almost half respondents reported low genomic confidence. Somatic mutation test ordering was higher amongst oncologists and those with increased confidence in interpreting somatic variants. It is unclear whether genomically confident individuals ordered more tests or whether ordering more tests increased genomic confidence. Educational interventions could improve confidence and enhance test ordering behaviour.

Background Population-wide screening for melanoma is not cost-effective, but genetic characterisation could facilitate risk stratification and targeted screening. Common MC1R red hair colour (RHC) variants and MITF E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. Objectives Evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ versus E318K- individuals. Methods Melanoma affection status and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank respectively). Chi-square and logistic regression evaluated RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200,000 general population exomes (UK Biobank). Results The cohort comprised of 1,165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild-type (wt), p&lt;0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (p&lt;0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to wt allele (OR=2.04, 95% CI [1.67, 2.49], p=0.01), while the r allele risk was comparable to wt allele (OR=0.78, 95% CI [0.54,1.14] vs 1.00 respectively). E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt (OR=0.52, 95% CI [0.20,1.38]). Within the E318K+ cohort, R genotypes (R/R, R/r, and R/wt) conferred a significantly higher risk compared to non-R genotypes (r/r, r/wt and wt/wt) (p&lt;0.001). UK Biobank data supporting our findings that r did not increase melanoma risk in E318K+ individuals. Conclusions RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable to wt. These findings could inform counselling and management for MITF E318K+ individuals.

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Background: Clinical whole exome sequencing was introduced in an Australian centre in 2017, as an alternative to Sanger sequencing. We aimed to identify predictors of cancer physicians’ somatic mutation test ordering behaviour. Methods: A validated instrument assessed somatic mutation test ordering, genomic confidence, perceived utility of tumour molecular profiling, and percent of patients eligible for targeted therapy. A cash incentive was included in 189/244 questionnaires which were mailed to all Queensland cancer specialists in November 2018. Results: 110 participated (response rate 45%); 54.7% oncologists, and the remainder were surgeons, haematologists and pulmonologists. Oncologists were more likely to respond (p=0.008), and cash incentive improved the response rate (p<0.001). 67/102 (65.7%) of physicians ordered ≥5 somatic mutation tests annually. Oncologists saw 86.75 unique patients monthly and ordered 2.33 somatic mutation tests (2.2%). An average of 51/110 (46.1%) reported having little/no genomic confidence. Logistic regression identified two significant predictors of somatic mutation test ordering: being an oncologist (OR 3.557, CI 1.338-9.456; p=0.011) and having greater confidence in interpreting somatic results (OR 5.926, CI 2.230-15.74; p<0.0001). Conclusions: Consistent with previous studies, the majority of cancer physicians ordered somatic mutation tests. However, the percentage of patients on whom tests were ordered was low. Almost half respondents reported low genomic confidence. Somatic mutation test ordering was higher amongst oncologists and those with increased confidence in interpreting somatic variants. It is unclear whether genomically confident individuals ordered more tests or whether ordering more tests increased genomic confidence. Educational interventions could improve confidence and enhance test ordering behaviour.