Recommendations on prevention and screening for colorectal cancer in Hong Kong.

Colorectal cancer is the commonest cancer in Hong Kong. The Cancer Expert Working Group on Cancer Prevention and Screening was established in 2002 under the Cancer Coordinating Committee to review local and international scientific evidence, assess and formulate local recommendations on cancer prevention and screening. At present, the Cancer Expert Working Group recommends that average-risk individuals aged 50 to 75 years and without significant family history consult their doctors to consider screening by: (1) annual or biennial faecal occult blood test, (2) sigmoidoscopy every 5 years, or (3) colonoscopy every 10 years. Increased-risk individuals with significant family history such as those with a first-degree relative diagnosed with colorectal cancer at age ≤60 years; those who have more than one first-degree relative diagnosed with colorectal cancer irrespective of age at diagnosis; or carriers of genetic mutations associated with familial adenomatous polyposis or Lynch syndrome should start colonoscopy screening earlier in life and repeat it at shorter intervals.

Recommendations on prevention and screening for breast cancer in Hong Kong.

In Hong Kong, breast cancer is the most common cancer among women and poses a significant health care burden. The Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) was set up in 2002 by the Cancer Coordinating Committee to review and assess local and international scientific evidence, and to formulate recommendations for cancer prevention and screening. After considering the local epidemiology, emerging scientific evidence, and local and overseas screening practices, the CEWG concluded that it was unclear whether population-based breast cancer screening did more harm than good in local asymptomatic women at average risk. The CEWG considers that there is insufficient evidence to recommend for or against population-based mammography screening for such individuals. Women who consider breast cancer screening should be adequately informed about the benefits and harms. The CEWG recommends that all women adopt primary preventive measures, be breast aware, and seek timely medical attention for suspicious symptoms. For women at high risk of breast cancer, such as carriers of confirmed BRCA1/2 deleterious mutations and those with a family history of breast cancer, the CEWG recommends that they seek doctor's advice for annual mammography screening and the age at which the process should commence. Additional annual screening by magnetic resonance imaging is recommended for confirmed BRCA1/2 mutation carriers or women who have undergone radiation therapy to the chest between the age of 10 and 30 years. Women at moderate risk of breast cancer should discuss with doctors the pros and cons of breast cancer screening before making an informed decision about mammography screening every 2 to 3 years.

The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.

BACKGROUND: The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance. METHODS: C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment. RESULTS: The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73. CONCLUSION: Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

Oct4 is epigenetically regulated by methylation in normal placenta and gestational trophoblastic disease.

Oct4 is a transcription factor that plays a crucial role in maintaining pluripotency of embryonic stem cells. Down-regulation of Oct4 is associated with the differentiation of trophectoderm cell lineage, from which the normal placenta derives. We investigated the methylation and expression status of Oct4 in normal placenta and gestational trophoblastic disease (GTD) as attempts to investigate the role of Oct4 in the pathogenesis of GTD. By methylation-specific PCR, we observed both methylated and unmethylated Oct4 alleles in all 25 first trimester and 10 term placentas while 33% (18/54) of hydatidiform moles, and two choriocarcinoma cell line (JEG3 and JAR), only displayed methylated Oct4 allele. By quantitative TaqMan real-time PCR, Oct4 mRNA was significantly reduced in hydatidiform moles (P=0.04), JEG3 and JAR (P=0.024) when compared with normal placentas. Oct4 methylation was significantly correlated with Oct4 mRNA expression in placenta and GTD (P=0.012). Hypermethylation in minimal promoter and exon 1 region of Oct4 were confirmed in JEG3 and JAR by bisulfite genomic sequencing. The Oct4 mRNA expression in JEG3 and JAR increased after treatment with 5-aza-2'-deoxycytidine and/or trichostatin A. Our findings suggest that Oct4 is down-regulated by hypermethylation in normal placenta and GTD and such process is important in pathogenesis of GTD.