Analysis of breast cancer susceptibility genesBRCA1 andBRCA2 in Thai familial and isolated early-onset breast and ovarian cancer

Abstract

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.

Founder mutation in the BRCA1 gene in Malay breast cancer patients from Singapore

“…There are numerous reports on founder mutations of the BRCA1 gene in Ashkenazi Jews and Caucasian populations (Iau et al, 2001). In Asia, possible founder mutations in BRCA1 in breast cancer patients have been reported in Japanese (Ikeda et al, 2001), Pakistanis , Thais (Patmasiriwat et al, 2002) and Filipinos (De Leon Matsuda et al, 2002). The BRCA1 5454delC mutation was detected in two Filipino patients of Malay/Hispanic ancestry (De Leon Matsuda et al, 2002), but it was not seen in Malay patients in this study.…”

“…In Asia, founder mutations of the BRCA1 gene have been reported in breast or ovarian cancer patients in Japanese (Ikeda et al, 2001, Sekine et al, 2001, Chinese , Pakistanis , Thais (Patmasiriwat et al, 2002), and Filipinos (De Leon Matsuda et al, 2002), but none yet for Malays.…”

Evidence for an ancient BRCA1 mutation in breast cancer patients of yoruban ancestry

“…BRCA1 and BRCA2 founder mutations have been identified in different European populations, including Belgian [7], French-Canadian [8], German [9], Spanish [10] and Swedish [11] populations. Several studies have also reported BRCA1 and BRCA2 founder mutations in Asian populations including Chinese [12], Japanese [13], Malay [14], Thai [15] and Filipino [16] populations. However, thus far, only one mutation (BRCA1 943ins10) has been identified as a potential founder mutation in patients of West African ancestry [17], and the frequency of this mutation in breast cancer patients of African ancestry has not been determined.…”

Breast Cancer Associated Mutations Reported Among Malaysian Malay, Chinese and Indian Patients

“…Y856H mutation has been previously reported in cancer-free individuals of Chinese descent in Hong Kong [22] and Shanghai [26] , suggesting that the variant is neutral and unlikely to contribute to breast cancer risk. However, this mutation was found to cause high risk of breast/ovarian cancer in Thailand [31] .…”