BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.
METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.
RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.
CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
p53 is the most commonly mutated tumour-suppressor gene in human cancers. Unlike other tumour-suppressor genes, most p53 cancer mutations are missense mutations within the core domain, leading to the expression of a full-length mutant p53 protein. Accumulating evidence has indicated that p53 cancer mutants not only lose tumour suppression activity but also gain new oncogenic activities to promote tumourigenesis.
Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence.
Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.
Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.
Cancer incidence during 1972-90 in Asian migrants to New South Wales, Australia, is described. Overall cancer incidence was lower than in the Australia born in most migrant groups, and this reached significance in migrants born in China/Taiwan, the Philippines, Vietnam and India/Sri Lanka, and in male migrants born in Indonesia. For the majority of cancers, rates were more similar to those in the Australia born than to those in the countries of birth. For cancers of the breast, colorectum and prostate, rates were relatively low in the countries of birth, but migrants generally exhibited rates nearer those of the Australia born. For cancers of the liver and cervix and, in India/Sri Lanka-born migrants, of the oral cavity, incidence was relatively high in the countries of birth but tended to be lower, nearer Australia-born rates, in the migrants. For these cancers, environmental factors related to the migrant's adopted country, and migrant selection, appeared to have a major effect on the risk of cancer. For certain other cancers, incidence was more similar to that in the countries of birth. Nasopharyngeal cancer, and lung cancer in females, had high rates in both the countries of birth and in migrants to Australia. Nasopharyngeal cancer rates were highest in China/Taiwan and Hong Kong-born migrants, and were also significantly high in migrants from Malaysia/Singapore, Vietnam and the Philippines. Rates of lung cancer were significantly high in women born in China/Taiwan, and the excess was greater for adenocarcinoma than for squamous cell carcinoma. Melanoma had low rates in both the migrants and in the countries of birth. For these cancers, it was probable that genetic factors, or environmental factors acting prior to migration, were important in causation.
Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.
Herbal medication has been practised by the rural Malaysian Malays for a long time. However, the long-term side-effects have never been studied. In the present study, 48 species of Euphorbiaceae were screened for tumour-promoter activity by means of an in vitro assay using a human lymphoblastoid cell line harbouring the Epstein-Barr virus (EBV) genome. Twenty-seven per cent (13 out of 48) of the species tested were found to be positive, and in four species, namely Breynia coronata Hk.f, Codiaeum variegatum (L) Bl, Euphorbia atoto and Exocoecaria agallocha, EBV-inducing activity was observed when the plant extracts were tested at low concentrations of between 0.2 and 1.2 micrograms ml-1 in cell culture. This observation warrants attention from the regular users of these plants because regular use of plants with tumour-promoting activity could well be an aetiological factor for the promotion of tumours among rural Malaysian Malays.
HLA associations were observed in unrelated Malay patients with nasopharyngeal carcinoma (NPC). HLA-B18 was observed in 18/45 (40%) Malay NPC patients compared to 22/167 (13%) Malay normals (P = 0.0001; Pc = 0.0027, RR = 4.4). The frequency of HLA-B17, one of the antigens associated with Chinese NPC, was also increased among Malay NPC (13/45 29%) compared to controls (18/167 11%; P = 0.003, Pc = 0.07 RR = 3.4). Similar to the findings among Chinese NPC, the frequency of B17 was higher in early onset (less than or equal to 30 years) Malay NPC resulting in a higher relative risk (RR = 5.0).
A record of all known cases of nasopharyngeal carcinoma in Malaysia is complete for 10 years from 1968 to 1977. Special efforts in case-finding were made in the State of Selangor where conditions are optimal. Age-adjusted incidence rates among Chinese males and females were 16.5 and 7.2 per 100,000, among Malay males and females 2.3 and 0.7 and among Indian males, 1.0. There were no significant changes in incidence rates over the 10-year period for sex and ethnic groups, or for Chinese subethnic groups. In Chinese subethnic groups, rates were highest among Cantonese, moderate among Khek and lowest among Hokkien and Teochiu. Standardized incidence ratios using Selangor as the standard population indicate considerable under-reporting in the less urban states of Malaysia, particularly among females. In Selangor, incidence rates were similar for urban and rural residents, but the frequency of cases was higher among Chinese working in industry and living in poor neighbourhoods.
Sixty-two "leukoplakias" from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the "intensity" of the habit.
Changes in the buccal mucosa of 296 Indian and Malay betel-nut chewers in Perak, West Malaysia, were studied clinically. 167 out of 212 Indian subjects incorporated tobacco in their quids, while 45 out of 84 Malay subjects incorporated. "Gambir". The Indians appeared to show a higher proportion of mucosal changes, particularly when tobacco was used. "Gambir" did not appear to be potent in the production of mucosal changes. Comparison with studies in other parts of the world suggested comparable findings with respect to both tobacco and non-tobacco chewing samples, and there would appear to be some evidence that tobacco-containing quids are likely to produce a higher proportion of mucosal changes as compared to non-tobacco-containing quids. An attempt to demonstrate a dose-effect relationship by dividing the subjects into "slight" and "heavy" chewers did not yield significant differences between these two categories in each of the groups.