Seybolt L M, Vachon C, Potter K, Zheng W, Kushi L H, McGovern P G, Sellers T A
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, 55454-1015, USA.
Genet Epidemiol. 1997;14(1):85-95. doi: 10.1002/(SICI)1098-2272(1997)14:1<85::AID-GEPI7>3.0.CO;2-4.
Systematic errors, or bias, can arise at several stages of a study, including selection of subjects, measurement of exposure and disease, and data analysis. Little attention appears to have been paid to potential sources of bias in genetic epidemiologic studies, despite the fact that the study of units (families) and members (relatives) within those units produces unique opportunities for bias to be introduced. The ability to evaluate whether selection bias has occurred is rare. In 1944, a case-control family study of breast cancer was initiated at the Dight Institute for Human Genetics at the University of Minnesota. A follow-up study of these 544 families is currently being conducted on sisters, daughters, nieces, and granddaughters of the probands, and a control group of women who are spouses of male first- and second-degree relatives. Updated data are collected on females who are 18 years or older through telephone interviews and questionnaires. The availability of detailed family history information on these families at baseline provided an opportunity to evaluate several potential sources of bias. Analyses were performed to determine if families lost to follow-up differed from those who were successfully located or excluded (ineligible), and whether participation rates within a family differed by relationship to proband, age, and family history of cancer. The latter participation rates for individuals were examined with respect to a telephone interview, a mailed questionnaire, and screening mammography. There were no statistically significant differences in the cancer histories of families that were excluded, those that were lost to follow-up, and those that participated. Within families, degree of relationship to the breast cancer proband was significantly associated with age-adjusted participation rates on mailed questionnaires (P < 0.005) and mammography (P < 0.005), but not telephone interviews (P = 0.29). After adjustment for age, marry-ins with a family history of breast cancer were not significantly more likely than marry-ins without a family history to undergo mammography (P = 0.11) or return mailed questionnaires (P = 0.74). Although non-participation is a potentially serious source of bias to a genetic epidemiologic study and the effect of variable participation rates should be explored when investigating the genetic component of a disease, it does not appear to be a problem for this particular study.
系统误差或偏倚可能在研究的多个阶段出现，包括研究对象的选择、暴露和疾病的测量以及数据分析。尽管基因流行病学研究中单位（家庭）及其成员（亲属）的研究会带来引入偏倚的独特机会，但对潜在偏倚来源的关注似乎很少。评估是否发生选择偏倚的能力很罕见。1944年，明尼苏达大学迪特人类遗传学研究所启动了一项乳腺癌病例对照家庭研究。目前正在对这些544个家庭的先证者的姐妹、女儿、侄女和孙女以及男性一级和二级亲属的配偶组成的对照组进行随访研究。通过电话访谈和问卷调查收集18岁及以上女性的最新数据。这些家庭在基线时可获得详细的家族史信息，这为评估几个潜在的偏倚来源提供了机会。进行分析以确定失访家庭与成功找到或排除（不符合条件）的家庭是否不同，以及家庭内部的参与率是否因与先证者的关系、年龄和癌症家族史而异。针对电话访谈、邮寄问卷和乳腺钼靶筛查，检查了个体的后一种参与率。被排除的家庭、失访的家庭和参与的家庭在癌症病史方面没有统计学上的显著差异。在家庭内部，与乳腺癌先证者的关系程度与邮寄问卷（P<0.005）和乳腺钼靶检查（P<0.005）的年龄调整后参与率显著相关，但与电话访谈（P = 0.29）无关。在调整年龄后，有乳腺癌家族史的嫁入者接受乳腺钼靶检查（P = 0.11）或返还邮寄问卷（P = 0.74）的可能性并不比没有家族史的嫁入者显著更高。尽管不参与是基因流行病学研究中一个潜在的严重偏倚来源，并且在研究疾病的遗传成分时应探讨可变参与率的影响，但对于这项特定研究而言，这似乎不是一个问题。
