具乳癌家族病史婦?之乳癌危險因子探討

Risk factors of breast cancer for women with family history

黃昭仁(Chao-Jen Huang)

指導教授 ： 洪清霖 ； 陳秀熙

臺北醫學大學/公共衛生暨營養學院/公共衛生學研究所/碩士(2005年)

摘要

研究背景 女性乳癌是台灣地區目前發生率第二高的癌症，雖然在過去已經有許多研究致力於瞭解乳癌發生的危險因子；然而，如何在同時受內在遺傳因子暴露的當中去釐清鑑別外在環境因子對於乳癌發生危險性的影響，仍有待相關的研究探討。相較於西方國家，臺灣地區的乳癌發生率的高峰出現在較為年輕的族群--45 歲左右。乳癌家族病史已被證實對於較年輕女性的族群具有增加乳癌發生的危險性，因此，闡明其他乳癌危險因子(例如：生殖學因子)可能會造成的影響，對於本身具有乳癌家族病史的女性而言就顯得更加重要了。本論文的目的欲藉由一個以醫院為主體所蒐集的乳癌高危險族群篩檢世代追蹤資料，探討具有乳癌家族病史女性族群之乳癌危險因子。 研究材料 與研究工具本研究的樣本皆來自於一個以醫院為主體的篩檢計畫--TAMCAS(臺灣多中心癌症篩檢計畫)中具有乳癌家族病史的受檢女性，個案邀請自臨床女性乳癌病患之ㄧ等親及二等親女性親屬接受篩檢，收案期間為1994~1998 年間，共4867 名女性接受篩檢。來自同一個家系的參與者視為具有同一組家戶編碼，先以羅吉式迴歸模式調查具有統計上顯著意義的危險因子(假定所有參與者皆不具家系相關聯性的獨立個體)，再進一步以廣義估計方程式模式進行分析調查，以考慮參與者的家族相依特性。結果經由羅吉式迴歸多變項分析的結果，具有統計上顯著相關者有：年齡的增加、月經規則者、較少的生產次數或從未生產、高教育程度以及無職業者。由於年齡與BCMA 彼此具有相關，因此在排除年齡變項的影響後，可以獲得另一個模式，其變項包括：終生BCMA、月經規則者、較少的生產次數或從未生產、已停經者以及家族中具有三名以上一等親乳癌患者。同樣的發現也出現在廣義估計方程式模式當中。在廣義估計方程式模式中危險因子包括：年齡增加、月經規則者；另外初經年齡的增加與曾經避孕則呈現保護作用。在排除年齡變 項後，另一模式為：終生BCMA 越長者、月經規則者、已停經、較少的生產次數或從未生產以及家族中具有三名以上一等親乳癌患者。 結論 在本研究當中，我們證實了遺傳因子與生殖學因子對於具有乳癌家族病史之女性族群其乳癌發生的危險性皆扮演著相當重要的角色。建立這樣一個預測模型或許能對於具有乳癌家族病史之女性族群這樣的高危險群，在於乳癌防治上有所助益。

關鍵字

乳癌 ； 乳癌家族病史 ； 高危險群 ； 廣義估計方程式 ； 相依特性

並列摘要

Background Female breast cancer was the second leading incidence of malignant tumors and of female cancers in Taiwan. Although there were a great deal of investigations focusing on the elucidation of risk factors of developing breast cancer, the distinguishing of environment factors from genetic factors still attracts great interests. In addition, as the peak of incidence rate in Taiwan is around 45 years of age, which is earlier compared with western countries. As familial effects have been recognized as increasing in younger women, the elucidation of risk factors such as reproductive factors for the risk of breast cancer in women with positive family history of breast cancer is therefore of paramount important. In the current thesis, we aimed to investigate the risk factors for breast cancer among women with family history from a hospital-based high-risk cohort with breast cancer screening with consideration of correlation in the cohort. Materials and methods A total of 4867 women in the current study was included from a hospital-based screening program, Taiwan Multicentre Cancer Screening Project (TAMCAS), for women with female breast cancer within second-degree relatives underwent breast cancer screening between 1994 and 1998. Subjects from the same family were treated as in one family proband. Logistic regression models were firstly used to investigate the effect of different risk factors assuming independency among participants regardless family probands. Generalized estimating equation (GEE) model was used to consider correlation among participants from the same family proband. Results The results of multi-variate analysis of logistic regression recognized risk factors of breast cancer included age, regularity of menses, smaller number of child birth or nullparity, higher level of education, and not employed. Since the correlation between age and period of lifetime CBMA, after excluding age the final model included lifetime BCMA, regularity of menses, smaller number of child birth or nullparity, menopause, and three or more first-degree relatives with breast cancer. The similar findings of univariate analysis from GEE model were found in both models with autoregressive and unstructured working correlation matrix. The GEE model included age, age at menarche, regularity of menses, and contraception as recognized risk factors. When excluding age from the multi-variate model, the significant factors retained in the model was lifetime BCMA, regularity of menses, number of child birth, menoparuse, and three or more first-degree relatives with breast cancer. Conclusion In the present study, we confirmed genetic factors and reproductive factors play respective important roles in the risk for developing breast cancer even in Taiwanese women with positive family history. The built-in predictive model may be helpful for prevention of women with family history.

並列關鍵字

Breast cancer ； GEE model ； family history ； proband

參考文獻

Andrieu N, Prevost T, Rohan TE, Luporsi E, Le MG, Gerber M, et al. Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality. Int J Epidemiol 2000; 29: 214-223.

Armstrong K, Eisen A, Weber B. Assessing the risk of breast cancer. NEJM. 2002; 342(8);564-71.

Andrieu N, Clavel F, Auquier A, Le MG, Gairard B, Piana L, et al. Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors. J Clin Epidemiol. 1993;46:973-80.

Andrieu N, Smith T, Duffy SW, Zaridze DG, Renaud R, Rohan T. The effects of interaction between familial and reproductive factors on breast cancer risk: a combined analysis of seven case-control studies. BJC 1998; 77: 1525-1536.

Bain C, Speizer FE, Rosner B, Belanger C, Hennekens CH. Family history of breast cancer as a risk indicator for the disease. Am J Epidemiol. 1980;111:301-8.