Alsbeih Ghazi A, Al-Harbi Najla M, Bin Judia Sara S, Khoja Hatim A, Shoukri Mohamed M, Tulbah Asma M
Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Pathology & Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Cancer. 2017 Jul 1;123(13):2459-2466. doi: 10.1002/cncr.30635. Epub 2017 Apr 10.
Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence.
Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples.
The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003).
Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society.
在全球范围内，宫颈癌主要是由人乳头瘤病毒（HPV）驱动的疾病。然而，在包括沙特阿拉伯在内的西亚地区，其发病率却低得令人费解。基于此范例，我们研究了HPV感染率和宿主遗传易感性在推测会影响癌症发病率的TP53 G72C单核苷酸多态性（SNP）中的作用。
回顾了1990年至2012年间接受治疗的患者，研究了232例浸润性宫颈癌病例，并与313例匹配的无癌对照进行比较。通过直接测序对SNP进行基因分型。采用HPV线性阵列分析检测肿瘤样本中的HPV并进行基因分型。
宫颈癌发病率在42.5岁时呈现双峰峰值，在60.8岁时略有反弹。在所有病例中，77%为HPV阳性，检测到16种HPV基因型，其中大多数为16型（75%）和18型（9%），在年龄、组织学或地理区域方面无差异。虽然TP53 G72C基因型与总体宫颈癌风险无关，但它与HPV阳性显著相关（比值比，0.57；95%置信区间，0.36 - 0.90；P = 0.016）。此外，变异的C等位基因在人群中显著过度传递（P < 0.0003）。
宫颈癌发病率呈双峰曲线，在年轻时达到峰值，在老年时出现二次反弹。相对较低的HPV感染率与变异的TP53 72C等位基因过度传递相结合，为我们人群中宫颈癌发病率较低提供了一个合理的解释。因此，HPV筛查和宿主SNP基因分型可能提供更相关的生物标志物来评估患宫颈癌的风险。《癌症》2017年；123:2459 - 66。© 2017美国癌症协会。
