Geographic distribution of liver and stomach cancers in Thailand in relation to estimated dietary intake of nitrate, nitrite, and nitrosodimethylamine.

It is our working hypothesis that the high rate of the liver and gastric cancers in North and Northeast Thailand is associated with increased daily dietary intake of nitrate, nitrite, and nitrosodimethylamine (NDMA). Samples of fresh and preserved Thai foods were systematically collected and analyzed from 1988 to 1996 and from 1998 to 2005. Consumption frequencies of various food items were determined on the basis of a dietary questionnaire given to 467 adults (212 males and 255 females) from 1998 to 2005. Food consumption data for the preceding and current year were collected and intakes (day, week, and month) of nitrate, nitrite, and NDMA were calculated. The trends in liver and stomach cancer age-standardized incidence rates (ASR) in four regions of Thailand were compared with the dietary intake of nitrate, nitrite, and NDMA in those same geographic regions. Mean daily intakes of nitrate of 155.7 mg/kg, of nitrite of 7.1 mg/kg, and of NDMA of 1.08 microg/kg per day were found. Significant differences in dietary nitrate, nitrite, and NDMA intakes were seen between various Thai regions (P < 0.0001), and these corresponded to the variations in liver and stomach cancer ASR values between the regions. Dietary factors are likely to play key roles in different stages of liver and stomach carcinogenesis in Thailand.

Contraception and breast cancer.

Oral contraceptive use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. Recent studies indicating that oral contraception may increase the risk of breast cancer more in subjects who are BRCA 1 or BRCA 2 mutation carriers. Features of hormonal contraceptive use, such as duration of use, age at first use, and the dose and type of hormone within the contraceptives, have little effect on breast cancer risk. Women who begin use before age 20 have higher relative risks of having breast cancer diagnosed while they are using combined oral contraceptives and in the 5 years after stopping than do women who begin use at older ages. Given that on influence of oral contraceptives on the breast has been hypothesized to be greatest before the cellular differentiation that occurs with a first pregnancy. A significant trend of increasing risk with first use before age 20 years was observed. Among women diagnosed at ages 30 to 34 years the relative risk associated with recent oral contraceptive use was 1.54 if use began before age 20 years and 1.13 it use began at older ages.

Rising leukemia rates in Thailand: the possible role of benzene and related compounds in cigarette smoke.

Epidemiological studies suggest that cigarette smoking is associated with an increased risk of leukemia and that benzene and related compounds in cigarette smoke may contribute to this elevated risk. This report presents new findings on selected components of cigarette smoke (including benzene and 1,3-butadiene) from major brands of cigarettes sold in Thailand, which represent about 80% of market share. Tested were also two major and popular brands of U.S. cigarettes sold in Thailand, representing about 100% of market share. The cigarettes tested were filter and non-filter, and with high and 'low' tar and nicotine levels. The observed range for benzene, toluene and 1,3-butadiene were found in the range of 25.5-63.7, 36.4-79.8 and 44.6-78.7 microg/cigarette, respectively. The amount of acrolein ranged from 79.9-181 microg/cigarette and for isoprene from 313-694 microg/cigarette. Yields of these substances showed no correlation with tar deliveries in mainstream smoke. Consumption of tobacco products increased in Thailand since 1970. This study also showed increases in leukemia mortality rates in Thailand, and in the relative frequency of leukemia among incident cancers diagnosed at a large hospital in Bangkok. Exposure to benzene and related compounds in cigarette smoke may have contributed to these trends. Analytic epidemiological studies are needed on the relationship between these compounds in smoke from tobacco products used in Thailand. These preliminary findings support the need for voluntary and/or government-regulated reduction in smoke yields of benzene and related compounds in tobacco products, and for expanded smoking prevention and cessation efforts, in Thailand.

Analysis of breast cancer susceptibility genes BRCA1 and BRCA2 in Thai familial and isolated early-onset breast and ovarian cancer.

Here we report the study on BRCA1 and BRCA2 mutations in 12 Thai breast and/or ovarian cancer families and 6 early-onset breast or breast/ovarian cancer cases without a family history of cancer. Five distinct rare alterations were identified in each gene: four introducing premature stop codons, one in-frame deletion, two missense changes, two intronic alterations and one silent rare variant. The BRCA1 or BRCA2 truncating mutations were detected in four of seven patients with familial or personal history of breast and ovarian cancer, in one of four isolated early onset breast cancer cases and in none of seven breast cancer site specific families. The BRCA1 and BRCA2 mutation yield in Thai patients is consistent with that reported from Europe and North America in similar groups of patients, being particularly high in individuals with personal or family history of breast and ovarian cancer. The BRCA1 and BRCA2 alterations found in this series are different from those identified in other Asian studies, and all but two have never been reported before. We report at least three novel deleterious mutations, the BRCA1 3300delA, BRCA1 744ins20 and BRCA2 6382delT. One in-frame deletion was also found, the BRCA2 5527del9, which seggregated within family members of breast-only cancer patients and was thought to be a cancer-related mutation. BRCA1 3300delA and Asp67Glu alterations were detected each in at least two families and thus could represent founder mutations in Thais.

Estrogen receptor-alpha mRNA in primary breast cancer: relationship to estrogen and progesterone receptor proteins and other prognostic factors.

The estrogen receptor (ER)-alpha protein and ER mRNA were measured in 314 primary breast cancer patients by enzyme immunoassay (EIA) and reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. The positivity of ER protein was 53% while of ER mRNA was 37.6%. A significant positive association between ER phenotype and ER mRNA was observed (r = 0.40, p < 0.0001) with a positive-negative agreement between them of 71.8%. The percentage of ER-negative, progesterone receptor (PR)-positive breast tumors was 1.9% by EIA and 7% by RT-PCR assay. This may indicate a difference in ER variants in these studied patients. The ER protein and ER mRNA status were inversely related to tumor size and p53 positivity. Also, ER protein was frequently positive in patients with a higher number of lymph node invasions, well to moderate nuclear differentiated tumor cells and negative c-erbB-2 status. The difference of the ER or ER mRNA status regarding ages, menopausal status, tumor stages and histological types was not shown. In the present study, ER mRNA did not demonstrate a closer relationship to prognostic indicators of breast cancer than ER protein. Before including the ER mRNA assessment in routine investigations of breast cancer, its relationship to prognostic factors and survival outcome should be further assessed with a higher number of patients and a longer follow-up time.