控制环境因素可有效降低乳腺癌的发病率
导读：一项研究确认，遗传因素和环境因素对乳腺癌发病风险的影响是相互独立的，控制环境因素可有效降低乳腺癌的发病率。相关研究成果发表在最近一期的《柳叶刀》杂志上。
乳腺癌的风险因素包括环境（生活方式和行为等）因素和遗传因素两大类，其中环境因素，如激素替代疗法的使用、生育历史、肥胖、饮酒等，是引发乳腺癌的主要原因。而遗传因素是否会与环境因素相互作用，从而进一步增加患病风险，学界一直没有明确。
牛津大学癌症疫学所的研究人员对英国7160名乳腺癌患者和10196名健康妇女的基因和环境因素信息进行了研究。通过对12个和乳腺癌相关的常见基因变异与10个乳腺癌环境风险因素，包括生育次数、生育第一胎时的年龄、是否母乳喂养、是否使用激素替代疗法、肥胖、饮酒等，进行比较研究后确认，这两类风险因素之间并不存在相互作用的情况，即使是激素替代疗法也不会对遗传因素产生影响。也就是说，基因变异与不良生活方式都会增加罹患乳腺癌的风险，但二者互不相干。
需要指出的是，12个变异基因中不包括罕见的乳腺癌易感基因BRCA1和BRCA2。这两个基因携带者罹患乳腺癌的风险很高，但有此基因变异的人也很少。
研究人员指出，确认遗传因素和环境因素这两种风险因素间的关系可使医生更好地理解它们对乳腺癌的影响。在罹患乳腺癌的妇女中，受遗传因素影响发病的比例并不大，大多数妇女患病的原因要归罪于环境因素，而这些因素是可以人为控制的。因此，通过对环境风险因素的控制，就可以在很大程度上降低乳腺癌的发病率。(生物谷Bioon.com)
生物谷推荐原文出处：
The Lancet doi:10.1016/S0140-6736(10)60636-8
Gene—environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study
Dr Ruth C Travis DPhil a , Gillian K Reeves PhD a, Jane Green MD a, Diana Bull a, Sarah J Tipper MSc a, Krys Baker a, Prof Valerie Beral FRS a, Prof Richard Peto FRS b, Prof John Bell FRS c, Diana Zelenika PhD d, Prof Mark Lathrop PhD d, for the Million Women
Background
Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene—environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study.
Methods
We tested gene—environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption).
Findings
After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene—environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1—162·7] vs 163·1 cm [162·9—163·2]; p=0·01 after allowance for multiple testing).
Interpretation
Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors.
Funding
Cancer Research UK and the UK Medical Research Council.
牛津大学癌症疫学所的研究人员对英国7160名乳腺癌患者和10196名健康妇女的基因和环境因素信息进行了研究。通过对12个和乳腺癌相关的常见基因变异与10个乳腺癌环境风险因素，包括生育次数、生育第一胎时的年龄、是否母乳喂养、是否使用激素替代疗法、肥胖、饮酒等，进行比较研究后确认，这两类风险因素之间并不存在相互作用的情况，即使是激素替代疗法也不会对遗传因素产生影响。也就是说，基因变异与不良生活方式都会增加罹患乳腺癌的风险，但二者互不相干。
需要指出的是，12个变异基因中不包括罕见的乳腺癌易感基因BRCA1和BRCA2。这两个基因携带者罹患乳腺癌的风险很高，但有此基因变异的人也很少。
研究人员指出，确认遗传因素和环境因素这两种风险因素间的关系可使医生更好地理解它们对乳腺癌的影响。在罹患乳腺癌的妇女中，受遗传因素影响发病的比例并不大，大多数妇女患病的原因要归罪于环境因素，而这些因素是可以人为控制的。因此，通过对环境风险因素的控制，就可以在很大程度上降低乳腺癌的发病率。(生物谷Bioon.com)
生物谷推荐原文出处：
The Lancet doi:10.1016/S0140-6736(10)60636-8
Gene—environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study
Dr Ruth C Travis DPhil a , Gillian K Reeves PhD a, Jane Green MD a, Diana Bull a, Sarah J Tipper MSc a, Krys Baker a, Prof Valerie Beral FRS a, Prof Richard Peto FRS b, Prof John Bell FRS c, Diana Zelenika PhD d, Prof Mark Lathrop PhD d, for the Million Women
Background
Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene—environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study.
Methods
We tested gene—environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption).
Findings
After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene—environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1—162·7] vs 163·1 cm [162·9—163·2]; p=0·01 after allowance for multiple testing).
Interpretation
Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors.
Funding
Cancer Research UK and the UK Medical Research Council.
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