Thompson Deborah, Szabo Csilla I, Mangion Jon, Oldenburg Rogier A, Odefrey Fabrice, Seal Sheila, Barfoot Rita, Kroeze-Jansema Karin, Teare Dawn, Rahman Nazneen, Renard Hélène, Mann Graham, Hopper John L, Buys Saundra S, Andrulis Irene L, Senie Ruby, Daly Mary B, West Dee, Ostrander Elaine A, Offit Ken, Peretz Tamar, Osorio Ana, Benitez J, Nathanson Katherine L, Sinilnikova Olga M, Olàh Edith, Bignon Yves-Jean, Ruiz Pablo, Badzioch Michael D, Vasen Hans F A, Futreal Andrew P, Phelan Catherine M, Narod Steven A, Lynch Henry T, Ponder Bruce A J, Eeles Ros A, Meijers-Heijboer Hanne, Stoppa-Lyonnet Dominique, Couch Fergus J, Eccles Diana M, Evans D Gareth, Chang-Claude Jenny, Lenoir Gilbert, Weber Barbara L, Devilee Peter, Easton Douglas F, Goldgar David E, Stratton Michael R
CRC Genetic Epidemiology Unit, Strangeways Research Laboratories, University of Cambridge, Cambridge CB1 4RN, United Kingdom.
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):827-31. doi: 10.1073/pnas.012584499. Epub 2002 Jan 15.
The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (alpha) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (alpha = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at alpha = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.
已知的乳腺癌易感基因，包括BRCA1和BRCA2，仅占该疾病家族聚集性的一小部分。最近一项针对来自斯堪的纳维亚半岛的77个多病例乳腺癌家族的研究发现，该疾病与13号染色体q21区域的多态性标记之间存在连锁证据。我们评估了这个候选的“BRCA3”基因座对128个西欧血统的高危乳腺癌家族乳腺癌易感性的贡献，这些家族未检测到BRCA1或BRCA2突变。未发现连锁证据。在D13S1308（由凯努等人[(2000)《美国国家科学院院刊》97, 9603 - 9608]估计的位置）与易感基因座连锁的家族的估计比例（α）为0（95%置信上限为0.13）。对因基于BRCA2的连锁证据选择家族可能导致的偏差进行校正，并未实质性改变这一结果（α = 0，95%置信上限为0.18）。我们的数据集中以高度置信度排除了凯努等人报告的连锁家族比例（0.65）[α = 0.65时的异质性对数优势比（HLOD）为 -11.0]。我们得出结论，即使该基因座存在一个易感基因，它也只能解释一小部分非BRCA1/2的早发性乳腺癌多病例家族。
