Replacement of Fhit in cancer cells suppresses tumorigenicity

The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5′,5-P¹,P³-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase “dead” Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5′,5-P¹,P³-triphosphate hydrolysis is not required for tumor suppression.     

Iatrogenic mitral stenosis following transcatheter aortic valve replacement (TAVR)

A 57 year old female underwent transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. Mild iatrogenic mitral stenosis was noted intraoperatively. Attempts to reposition the device were hampered by aortic angulation. One year later, severe mitral stenosis was confirmed on transoesophageal echocardiography. It is important to recognise that iatorgenic mitral stenosis due to TAVR may progress over time. Care should be taken to minimise the risk of this rare complication     

Lifestyle and reproductive risk factors associated with anal cancer in women aged over 50 years

Background:

Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear.

Methods:

In all, 1.3 million women were recruited in 1996–2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors.

Results:

Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59–6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24–1.80); previous use of oral contraceptives (RR=1.51, 1.24–1.83); nulliparity (RR=1.61, 1.24–2.07); tubal ligation (RR=1.39, 1.13–1.70) and not living with a partner (RR=1.82, 1.40–2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04).

Conclusions:

History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas.