PTEN Promoter Variants Are Not Associated With Common Cancers: Implications for Multigene Panel Testing

Abstract

Purpose PTEN mutations are associated with breast, colon, endometrial, kidney, and thyroid cancers. Most PTEN promoter alterations, however, are characterized as variants of unknown significance, and their contribution to cancer risk is unclear. Materials and Methods Personal and family histories of 88,333 patients undergoing PTEN analysis as part of multigene panel testing (MGPT) were retrospectively reviewed. Cases (n = 59,784) were individuals with personal history of PTEN-related cancer. Controls (n = 28,549) had no personal history of cancer. Individuals were categorized as positive for one or more mutations (PATHO), without mutations but carrying one or more promoter variant (PROM), or negative for alterations (WT). Multivariable logistic regression was used to assess PTEN associations with phenotypes, adjusted for race/ethnicity, age, sex, and MGPT. Results Overall, 79 (0.09%) patients were PATHO and 791 (0.9%) were PROM carriers. Compared with WT, PATHOs were 2.30 (95% CI, 1.19 to 4.72) times as likely to have breast, 7.23 (95% CI, 2.74 to 19.14) times as likely to have bilateral/multiple primary breast, and 7.56 (95% CI, 1.97 to 23.98) times as likely to have uterine/endometrial cancer. PROMs were not significantly more likely than WT to have cancer (all 0.84 < odds ratio < 1.15; P > .05). Conclusion PTEN promoter variants were not associated with cancer. These results do not support the inclusion of PTEN promoter sequencing in MGPT.