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Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer
Sakamoto, Hiromi,Yoshimura, Kimio,Saeki, Norihisa,Katai, Hitoshi,Shimoda, Tadakazu,Matsuno, Yoshihiro,Saito, Daizo,Sugimura, Haruhiko,Tanioka, Fumihiko,Kato, Shunji,Matsukura, Norio,Matsuda, Noriko,Na Nature Pub. Co 2008 Nature genetics Vol.40 No.6
Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89, P = 1.11 × 10<SUP>−9</SUP>). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r<SUP>2</SUP> = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33, P = 8.01 × 10<SUP>−11</SUP>). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.
Sharon J.B. Hanley,Hiromasa Fujita,Satomi Aoyama-Kikawa,Mitsunori Kasamo,Toshihiko Torigoe,Yoshihiro Matsuno,Sakuragi Noriaki 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.6
Objective: While cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV+ women to avoid over-referral to colposcopy may be setting specific. We compared absolute and relative risk (RR) of >CIN2/3 within 12 months of a negative cytologic result in women HPV16/18+ compared to those with a 12-other high-risk HPV (hrHPV) genotype to identify women at greatest risk of high-grade disease and permit less aggressive management of women with other hrHPV infections. Methods: Participants were 14,160 women aged 25–69 years with negative cytology participating in the COMparison of HPV genotyping And Cytology Triage (COMPACT) study. Women who were HPV16/18+ were referred to colposcopy. Those with a 12-other hrHPV type underwent repeat cytology after 6 months and those with >abnormal squamous cells of undetermined significance went to colposcopy. Results: Absolute risk of >CIN2 in HPV16/18+ women was 19.5% (95% CI=12.4%–29.4%). In women 25–29 years and HPV16+ it was 40.0% (95% CI=11.8%–76.9%). Absolute risk of >CIN3 in women HPV16/18+ was 11.0% (95% CI=5.9%–19.6%). For women 30–39 years and HPV16+ it was 23.1% (95% CI=5.0%–53.8%). Overall risk of >CIN2, >CIN3 in women with a 12-other hrHPV HPV type was 5.6% (95% CI=3.1%–10.0%) and 3.4% (95% CI=1.6%–7.2%) respectively. RR of >CIN2, >CIN3 in HPV16/18+ vs. 12-other hrHPV was 3.5 (95% CI=1.7–7.3) and 3.3 (95% CI=1.2–8.8), respectively. Conclusion: Primary HPV screening with HPV16/18 partial genotyping is a promising strategy to identify women at current/future risk of >CIN2 in Japan without over-referral to colposcopy. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000013203