A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.

Summary To investigate risk factors for breast cancer in Taiwan, a low-incidence area, a case-control study was conducted. This comprised 244 subjects with diagnosed and pathologically confirmed breast cancer (age range 20-80 years) and 450 female ophthalmology outpatients as controls. Univariate and multiple logistic regression analysis suggests that breast cancer in Taiwan is aetiologically similar to breast cancer in high to moderate-incidence areas. A family history of breast cancer appears to be the most important factor contributing to the risk of breast cancer (odds ratio = 4.69). The effect of reproductive hormones (represented by the years of history of menses in premenopausal women, odds ratio = 3.35; or the age at menarche in post-menopausal women, odds ratio = 2.67) plays a significant role in tumorigenesis. Breast feeding appears to be a particularly important protective factor in Taiwanese women (odds ratio = 0.57).Keywords: breast cancer; cancer predisposition; reproductive hormone; breast feeding; risk factor; epidemiology Breast cancer is similar to other human cancers in that it arises from a multifactorial process. Recent attention has focused both on genetic predisposition to breast cancer (Sattin et al, 1985;Fisher et al, 1993) and on its association with factors relating to modem affluence, including diet and alcohol consumption (Hunter and Willett, 1993;Rosenberg et al, 1993). Furthermore, the effect of reproductive factors strongly supports a hormonal role in its aetiology Pike et al, 1993). Early menopause, for example, whether occurring naturally or through oophorectomy, has been shown to reduce risk significantly (Trichopoulos et al, 1973;Pike et al, 1981).While numerous studies have been conducted in Western countries to assess the epidemiology of breast cancer, there have been few studies of Asian populations. Such studies are of interest because their different risk profiles may help to explain the lower occurrence of the disease. Although breast cancer in Taiwanese women is the second most common form of cancer (Cancer Registry Annual Report in Taiwan, 1987-91) and the fourth leading cause of cancer mortality (based on Public Health Annual Report in Taiwan, 1993), compared with many Western countries Taiwan is considered to be a low-incidence area for breast cancer with an estimated age-adjusted incidence 15-20 per 100 000, which is much lower than the 60-90 per 100 000 in the UK or USA (Parkin et al, 1993 On the basis of hospital chart number, the cases were 244 women randomly selected from subjects with newly diagnosed (incident) and pathologically confirmed breast carcinoma in the age range 20-80 years. The histopathological profile included 227 cases of infiltrating ductal carcinoma and 17 cases of intraductal or intralobular carcinoma. This sample of female patients constituted about 30% of all the women with breast cancer attending our breast cancer clinic during the study period.To serve as comparable and representative controls, 450 (unmatched) women of the same age dist...