Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).
Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).
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DOI：
10.1186/bcr3218
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发表时间：
2012-07-03
期刊：
影响因子：
--
通讯作者：
Andrieu N
中科院分区：
文献类型：
--
作者：
Lecarpentier J;Noguès C;Mouret-Fourme E;Gauthier-Villars M;Lasset C;Fricker JP;Caron O;Stoppa-Lyonnet D;Berthet P;Faivre L;Bonadona V;Buecher B;Coupier I;Gladieff L;Gesta P;Eisinger F;Frénay M;Luporsi E;Lortholary A;Colas C;Dugast C;Longy M;Pujol P;Tinat J;GENEPSO;Lidereau R;Andrieu N
BRCA1和BRCA2突变会导致乳腺癌（BC）的高风险，但这种风险的大小似乎因研究和各种因素而异。尽管存在争议，但有数据支持等位基因风险异质性假说。在法国GENEPSO研究中，我们使用加权Cox回归模型，通过BRCA1和BRCA2均质危险区域的突变位置，根据与妊娠相关的因素评估了BC风险的变化。我们的研究结果证实，在BRCA1和BRCA2突变携带者中，不断增加的足月妊娠（FTPs）对BC的保护作用存在(≥3 vs 0 FTPs：风险比（HR) = 0.51, 95%可信区间(CI) = 0.33至0.81）。此外，HR显示不完全妊娠与更高的BC风险之间存在关联，与没有不完全妊娠的妇女相比，至少有三次不完全妊娠的妇女的风险达到2.39 （95% CI = 1.28至4.45）。这种增加的风险似乎仅限于第一次FTP前发生的不完全妊娠（HR = 1.77, 95% CI = 1.19至2.63）。我们定义了TMAP评分（定义为妊娠期间乳房有丝分裂活动时间），以同时考虑足月妊娠和妊娠中断的相反影响。与TMAP评分小于0.35的女性相比，TMAP评分升高与BC风险增加有统计学意义（P趋势= 0.02），TMAP评分为>.5（与TMAP≤0.35相比）的女性BC风险增加达到1.97 （95% CI = 1.19 ~ 3.29）。所有这些结果在BRCA1和BRCA2中似乎是相似的。然而，我们的结果表明，根据BRCA1突变的位置，BC风险与胎次相关。事实上，只有在BRCA1中心区域（低风险区域）发生突变的女性中，胎次似乎与BC风险的显著降低有关（FTP: HR = 0.27, 95% CI = 0.13至0.55）（p相互作用<10-3）。我们的研究结果表明，考虑到环境和生活方式的改变因素，突变位置可能对BRCA1和BRCA2突变携带者的临床管理很重要，也可能有助于理解BRCA1和BRCA2基因如何参与BC。
Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model. Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3). Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.
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