Ramachandran Dhanya, Dörk Thilo
Gynaecology Research Unit, Department of Gynaecology and Obstetrics, Comprehensive Cancer Center, Hannover Medical School, D-30625 Hannover, Germany.
Cancers (Basel). 2021 Oct 13;13(20):5137. doi: 10.3390/cancers13205137.
Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while many reports of associations with variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (), 17q12 (), and 5p15.33 () as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.
宫颈癌是全球女性中第四大常见癌症。在大多数情况下,高危型人乳头瘤病毒感染是必要条件,但并不足以引发浸润性宫颈癌。尽管预测其遗传度与其他妇科癌症相当,但迄今为止仅鉴定出少数基因组易感位点。多项病例对照关联研究已在6p21.3位点(HLA)发现了多个独立风险变异的佐证证据,而许多关于HLA区域以外变异的关联报道仍有待在其他队列中验证。在此,我们回顾了近期全基因组关联研究和大型队列荟萃分析中出现的宫颈癌易感变异,并提出2q14()、17q12()和5p15.33()作为经一致重复验证的非HLA宫颈癌易感位点。我们还进一步讨论了这些位点的现有证据、知识空白、未来展望,以及这些发现对对抗宫颈癌的精准医学策略的潜在影响。