臺灣博碩士論文加值系統

維生素D與乳癌之關係尚未有定論，且沒有相關研究在亞熱帶地區如台灣進行。本研究就飲食、陽光曝曬以及血液三方面探討維生素D與乳癌之關係。研究採取配對式病例對照研究，病例組與對照組的比例為1:1，總共有200對研究對象納入分析【配對條件為停經狀態、收案時間(±1個月)及抽血禁食時間(±4小時)】。以結構式問卷及半定量式飲食頻率問卷收集研究對象之基本資料、陽光曝曬資料及過去一年平均飲食攝取狀況。在校正年齡、教育程度、生產次數、女性荷爾蒙使用情形、BMI、總熱量攝取量以及每日陽光曝曬時間後，比較病例組與對照組之飲食維生素D攝取量及維生素D總攝取量，200 (IU/天) VS. 100 (IU/天)的乳癌OR值分別為0.51 (95% CI = 0.26- 0.98)及0.52 (95% CI=0.27-0.99) ，飲食部分並顯示出有劑量效應存在 (p for trend=0.04) 。以停經狀態及BMI進行分層，則發現飲食維生素D攝取量及維生素D總攝取量(含補充劑) ，均顯示對停經前婦女較具保護作用，在停經前的飲食維生素D攝取量並有劑量效應存在；血漿中25(OH)D濃度則對停經後婦女較具有保護作用，上述均未達統計顯著意義。以BMI分層，結果顯示飲食維生素D攝取量、維生素D總攝取量及血漿25(OH)D在相同四分位下，對BMI<24 kg/m2者較有保護作用。其中飲食維生素D攝取量Q4 VS. Q1之OR值為0.27 (95% CI=0.11-0.62) ，如果以Q2+Q3+Q4與Q1相比其OR值為0.46 (95% CI=0.23-0.90) ；維生素D總攝取量Q2+Q3+Q4其OR為0.51 (95% CI=0.26-0.99) ，皆指出對BMI<24的婦女而言，維生素D狀況與乳癌可能有閾值效應存在。陽光曝曬方面，發現每日待在室外時間超過60分鐘或工作時會曝曬到陽光者，其罹患乳癌機率較每日待在室外少於60分鐘或工作時不會曝曬到陽光者低。進一步以陽光曝曬時間分層去探討維生素D攝取量與乳癌相關性，結果指出每日維生素D攝取量超過200 IU並且每日陽光曝曬30分鐘以上者，罹患乳癌機率是較維生素D攝取量少於200 IU同時每日陽光曝曬30分鐘以下者低。本研究發現，即使在亞熱帶地區如台灣維生素D對於乳癌仍具有保護作用，尤其是在每日維生素D攝取量≧200 IU時。

The association between vitamin D and breast cancer is inconsistent and there is no relevant research in sub-tropical areas like Taiwan. The aim of the present hospital-based case-control study was to examine the relationship between breast cancer and vitamin D status assessed by diet, sun exposure and plasma 25(OH)D (in latitude 25°N). Two hundred women with newly diagnosed breast cancer in Taipei, Taiwan, and 200 controls were matched for menopausal status, blood drawing time ( 1 month) and fasting time before blood was drawn ( 4 hours). An interviewer-administered risk questionnaire was used to assess factors postulated as linked to breast cancer. Dietary intake one year prior to interview was assessed by a semi-quantitative questionnaire. After simultaneously controlling for age, education, parity, hormone replacement therapy, BMI, energy intake and daily sunlight exposure, the risk of breast cancer of those whose dietary or total vitamin D intake more than 200 IU/D was significantly lower than less 100 IU/d, the OR=0.51 (95% CI=0.26-0.98) and OR=0.52 (95% CI=0.27-0.99), respectively. After stratifying for menopausal status and BMI, both dietary and total vitamin D (with supplementation) intakes showed more evident protective effect among premenopausal women than among postmenopausal women. A significant linear trend, for breast cancer risk, in the dietary vitamin D intakes of premenopausal women was found. Plasma 25(OH)D concentration of postmenopausal women showed a similar protective effect against breast cancer though it was not significant. Among those women BMI was less than 24kg/m2, better vitamin D statuses (dietary, total vitamin D intake and plasma 25(OH)D) were inversely related to breast cancer risk. The OR of Q4 dietary vitamin D intake vs. Q1 was 0.27 (95% CI=0.11-0.62) and the OR of comparing quartile 2 through 4 together with subjects in the first quartile 1 was 0.46 (95% CI=0.23-0.90). The OR of Q2-Q4 total vitamin D intakes vs. Q1 was 0.51 (95% CI=0.26-0.99). Thus, a threshold effect of vitamin D status among subjects whose BMI was <24 was suggested. In terms of sunlight exposure, a lower risk of breast cancer was found among those who stayed outdoors more than 60 minutes per day. Those whose sunlight exposure was more than 30 min/day and vitamin D intake more than 200 IU/day had the lowest breast cancer risk of any other possible combination of these variables. In conclusion, a protective effect of vitamin D against breast cancer was evident in subtropical Taiwan, especially for vitamin D intake more than 200 IU/d.

第一章 背景及目的
第一節 前言
第二節 研究目的
第二章 文獻探討
第一節 乳癌之危險因子
壹、荷爾蒙相關因素
貳、體位
叁、飲食習慣
肆、其他
第二節 維生素D與乳癌
壹、維生素D的合成與代謝
貳、維生素D與癌症發生之相關機制
叁、維生素D與乳癌的關係
第三節 總結
第三章 研究假設
第四章 研究材料與方法
第一節 研究架構
第二節 研究設計
第三節 研究對象
壹、病例組選取方法
貳、對照組選取方法
第四節 研究工具
壹、問卷
貳、血液採集
第五節 資料處理及統計方法
壹、問卷信效度測試
貳、營養素計算分析
叁、統計方法
第五章 結果
第一節 人口學變項
第二節 體位資料
第三節 其他乳癌危險因子
第四節 維生素D營養狀況與乳癌之關係
壹、維生素D攝取量
貳、陽光曝曬情形
叁、血漿25(OH)D濃度
肆、分層分析
第六章 討論
第一節 乳癌危險因子
第二節 維生素D營養狀況與乳癌
壹、維生素D攝取量
貳、陽光曝曬情形
叁、血漿25(OH)D濃度
第三節 本研究之研究特性與限制
壹、研究特性
貳、研究限制
第七章 結論
參考文獻

1.Ainsleigh, H. G. (1993). Beneficial effect of sun exposure on cancer mortality. Prev Med, 22, 132-140.
2.Armas, L. A. G., Hollis, B. W., and Heaney, R. P. (2004). Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab, 89, 5387-5391.
3.Bertone-Johnson, E. R., Chen, W. Y., Michael, F. H., Bruce, W. H., Colditz, G. A., Willett, W. C., and Hankinson, S. E. (2005). Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev, 14, 1991-1997.
4.Blot, W. J., Fraumeni, J. F., and Stone, B. J. (1977). Geographic pattern of breast cancer in the United States. J Natl Cancer Inst, 59, 1407-1411.
5.Calvo, M. S., Whiting, S. J., and Barton, C. N. (2005). Vitamin D intake: a global perspective of current status. J Nutr, 135, 310-316.
6.Chapuy, M. C., Prezuosi, P., Maamer, M., Arnaud, S., Galan, P., Hercberg, S., and Meunier, P. J. (1997). Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int, 7, 439-443.
7.Colston, K. W. (2001). Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer, 9, 45-59.
8.Colston, K. W., Berger, U., and Coombes, R. C. (1989). Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet, 1, 188-191.
9.Deapen, D., Liu, L., Perkins, C., Bernstein, L., and Ross, R. K. (2002). Rapidly rising breast cancer incidence rates among Asian-American women. Int J Cancer, 99, 747-750.
10.Du, X., Greenfield, H., Fraser, D. R., Ge, K., Trube, A., and Wang, Y. (2001). Vitamin D deficiency and associated factors in adolescent girls in Beijing. Am J Clin Nutr, 74, 495-500.
11.Ellison, R. C., Zhang, Y., McLennan, C. E., and Rothman, K. J. (2001). Exploring the relation of alcohol consumption to risk of breast cancer. Am J Epidemiol, 154, 740-747.
12.Fournier, A., Berrino, F., Riboli, E., Avenel, V., and Clavel-Chapelon, F. (2005). Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer, 114, 448-454.
13.Freedman, D. M., Dosemeci, M., and McGlynn K. (2002). Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med, 59, 257-262.
14.Freudenheim, J. L., Marshall, J. R., Vena, J. E., Langhlin, R., Brasure, J. R., Swanson, M. K., and Nemoto, T. (1996). Premenopausal breast cancer risk and intake of vegetables, fruits and related nutrients. J Natl Cancer Inst, 88, 340-348.
15.Gannagé-Yared, M-E. Chemali, R., Yaacoub, N., and Halabym G. (2000). Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res, 15, 1856-1862.
16.Garland, C. F., Garland, F. C., Gorham, E. D., and Lipkin, M. (2006). The role of vitamin D in cancer prevention. Am J Public Health, 96, 252-261.
17.Garland, F. C., Garland, C. F., Gorham, E. D., and Young, J. F. (1990). Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med, 19, 614-622.
18.Giovannucci, E. (2005). The epidemiology of vitamin D and cacner incidence and mortality: a review (United States). Cancer Causes Control, 16, 83-95.
19.Giovannucci, E., Liu, Y., Rimm, E. B., Hollis, B. W., Fuchs, C. S., Stampfer, M. J., and Willett, W. C. (2006). Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst, 98, 451-459.
20.Gorham, E. D., Garland, F. C., and Garland, C. F. (1990). Sunlight and breast cancer incidence in the USSR. Int J Epidemiol, 19, 820-824.
21.Grant, W. B. (2002). An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer, 94, 272-281.
22.Harvie, M., and Howell, A. H. (2003). Central obesity and breast cancer risk: a systematic review. Obes Rev, 4, 157-173.
23.Hiatt, R. A., Krieger, B. L., Drezner, M. K., Vogelman, J. H., and Orentreich, N. (1998). Prediagnostic serum vitamin D and breast cancer. J Natl Cancer Inst, 90, 461-463.
24.Hilakivi-Clarke, L., Wang, C., Kalil, M., Riggins, R., and Pestell, R. G. (2004). Nutritional modulation of the cell cycle and breast cancer. Endocr Relat Cancer, 11, 603-622.
25.Holick, M. F. (1999). Vitamin D: physiology, molecular biology, and clinical applications. New Jersey: Humana.
26.Holick, M. F. (2004). Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr, 79, 362-371.
27.Hulka, B. S., and Moorman, P. G. (2001). Breast cancer: hormones and other risk factors. Maturitas, 38, 103-116.
28.Janowsky, E. C., Lester, G. E., Weinberg, C. R., Millikan, R. C., Schildkraut, J. M., Garrett, P. A., and Hulka, B. S. (1999). 29.Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr, 2, 283-291.
30.John, E. M., Schwartz, G. G., Dreon, D. M., and Koo, J. (1999). Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. Cancer Epidemiol Biomarkers Prev, 8, 399-406.
31.Kragballe, K. (2000). Vitamin D in dermatology. New York: Marcel Dekker.
32.Lee, W. P., Lin, L. W., Yeh, S. H., Liu R. H., and Tseng, C. F. (2002). Correlations among serum calcium, vitamin D and parathyroid hormone levels in the elderly in southern Taiwan. Journal of Nursing Research, 10, 65-70.
33.Lipkin, M., and Newmark, H. L. (1999). Vitamin D, calcium and prevention of breast cancer: a review. J Am Coll Nutr, 18, 392S-397S.
34.McCullough, M. L., Rodriguez, C., Diver, W. R., Feigelson, H. S., Stevens, V. L., Thun, M. J., and Calle, E. E. (2005). Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev, 14, 2898-2904.
35.Nakamura, K., Nashimoto, M., Hori, Y., and Yamamoto, M. (2000). Serum 25-hydroxyvitamin D concentrations and related dietary factors in peri- and postmenopausal Japanese women. Am J Clin Nutr, 71, 1161-1165.
36.Nakamura, K., Nashimoto, M., Matsuyama, S., and Yamamoto, M. (2001). Low serum concentrations of 25-hydroxyvitamin D in young adult Japanese women:a cross-sectional study. Nutrition, 17, 921-925.
Need, A. G., Morris, H. A., Horowitz, W., and Nordin, B. C. (1993). Effects of skin thickness, age, body fat, and sunligh on serum 25-hydroxyvitamin D. Am J Clin Nutr, 58, 882-885.
37.Parikh, S. J., Edelman, M., Uwaifo, G. I., Freedman, D. M., Semega-Janneh, M., Reynolds, J., and Yanovska, J. A. (2004). The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab, 89, 1196-1199.
38.Rahman, S. A., Chee, W., Yassin, Z., and Chan, S. (2004). Vitamin D status among postmenopausal Malaysian women. Asia Pac J Clin Nutr, 13, 255-260.
39.Robsahm, T. E., Tretli, S., Dahlback, A., and Moan, J. (2004). Vitamin D from sunligh may improve the prognosis of breast-, colon-, and prostate cancer (Norway). Cancer Causes and Control, 15, 149-158.
40.Scharla, S. H. (1998). Prevalence of subclinical vitamin D deficiency in different European countries. Osteoporos Int, 8, S7-S12.
41.Shin, M. H., Holmes, M. D., Hankinson, S. E., Wu, K., Colditz, G. A., and Willett, W. C. (2002). Intake of dairy products, calcium, and vitamin D and risk of breast cancer. J Natl Cancer Inst, 94, 1301-1311.
42.Tamimi, R. M., Hankinson, S. E., Campos, H., Spiegelman, D., Zhang, S., Colditz, G. A., Willett, W. C., and Hunter, D. J. (2005). Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol, 161, 153-160.
43.Tsai, K. S., Hsu, S. H. J., Cheng J. P., and Yang, R. S. (1997). Vitamin D stores of urban women in Taipei: effect on bone density and bone turnover, and seasonal variation. Bone, 20, 371-374.
44.van den Brandt, P. A., Spiegelman, D., Yaun, S. S., Adami, H. O., Besson, L., Folsom, A. R., Fraser, G., Goldbohm, R. A., Graham, S., Kushi, L., Marshall, J. R., Miller, A. B., Rohan, T., Smith-Warner, S. A., Speizer, F. E., Willett, W. C., Wolk, A., and Hunter, D. J. (2000). Pooled anaysis of prospective cohort studies on height. Am J Epidemiol, 152, 514-527.
45.Welsh, J. (2003). Vitamin D-3 receptor as a target for breast cancer prevention. J Nutr, 133, 2425S-2433S.
46.Welsh, J. (2004). Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr, 80, 1721S-1724S.
Willett, W. C. (1998). Nutritional epidemiology (2nd ed.). New York: Oxford University.
47.Willett, W. C. (2001). Diet and breast cancer. J Intern Med, 249, 395-411.
48.Wortsman, J., Matsuoka, L. Y., Chen, T. C., Lu, Z., and Holick, M. F. (2000). Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr, 72, 690-693.
49.Yager, J. D, and Davidson, N. E. (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med, 354, 270-82.
50.Yost, K., Perkins, C., Cohen, R., Morris, C., and Wright, W. (2001). Socioeconomic status and breast cancer incidence in California for different race/ethnic groups. Cancer Causes Control, 12, 730-711.
51.日本文部科學省。五訂增補日本食品標準成分表。日本文部科學省，2005。
http://www.mext.go.jp/b_menu/shingi/gijyutu/gijyutu3/toushin/05031802.htm
52.台北農產運銷股份有限公司。果菜運銷統計年報。台北農產運銷股份有限公司，2003。http://www.tapmc.com.tw/index1.asppic=3&change_frame=3&toolkey=F0302
53.行政院衛生署。91年癌症登記年報。行政院衛生署，2005。 http://crs.cph.ntu.edu.tw/crs_c/annual.html
54.行政院衛生署。1993~1996年國民營養健康狀況變遷調查報告。行政院衛生署，1998。http://www.ibms.sinica.edu.tw/~pan/nahsit/nahsit1/nahsit1.htm
55.行政院衛生署。國人飲食營養素參考攝取量。行政院衛生署食品衛生處，2002。
http://food.doh.gov.tw/chinese/libary/libary2_2_2.htm
56.行政院主計處。中華民國統計年鑑。行政院主計處，2004。 http://www.dgbas.gov.tw/public/data/dgbas03/bs7/yearbook/ch1/1-9&10.xls
57.行政院農委會。 漁獲供銷量統計年報，行政院農委會漁業署，2004。
http://www.fa.gov.tw/chn/index.php
58.行政院農委會，家畜產銷統計。行政院農委會畜牧處，2004。 http://bulletin.coa.gov.tw/view.php?catid=894
59.吳彩邑。葉酸與乳癌關係之病例對照研究。國防大學防國防醫學院公共衛生學研究碩士論文，2005。
60.美國農業部，增訂維生素D食物成分表，美國農業部，1991。
http://www.nal.usda.gov/fnic/foodcomp/search/
61.陳秀瑩、陳曉華、傅偉光。台灣地區食品營養成分資料庫（二）。食品工業發展研究所，2002。