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1 Clinical Article The Korean Journal of Sports Medicine 2018;36(4): pissn eissn 울트라마라톤이뇌하수체전엽및갑상선호르몬에미치는영향 신성대학교임상병리과 1, 성신여자대학교운동재활복지학과 2 신경아 1 ㆍ김영주 2 Effect of Ultramarathon on the Anterior Pituitary and Thyroid Hormones Kyung-A Shin 1, Young-Joo Kim 2 1 Department of Clinical Laboratory Science, Shinsung University, Dangjin, 2 Department of Exercise Rehabilitation Welfare, Sungshin University, Seoul, Korea Purpose: The purpose of this research is to study changes in pituitary hormone in anterior lobe and thyroid hormone before, after, and during recovery time in severe 100 km ultramarathon. M ethods: Healthy middle-aged runners (age, 52.0±4.8 years) participated in the test. Grade exercise test is done, and then blood is taken from those participants before and after completing 100 km ultramarathon at the intervals of 24 hours (1 day), 72 hours (3 days), and 120 hours (5 days) to analyze their luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free thyroxine (Free T4). Results: For LH, it decreased more significantly at 100 km than pre-race. However, after 1 day result increased more than that of 100 km. At 3 days, it was significantly higher than pre-race and 100 km, recovering at 5 days. In terms of FSH, it decreased at 100 km, 1 day, and 3 days more than pre-race but recovered at 5 days. TSH was higher at 1 day and 5 days compared to pre-race. T3 was only higher at 100 km than pre-race. T4 was higher till 5 days at 100 km than pre-race. Free T4 increased more significantly at 100 km than pre-race. Conclusion: In terms of severe long distance running, LH and FSH which belong to hormone from anterior lobe as well as T3, T4, and Free T4 which belong to thyroid hormone showed their variation within the standard range. However, TSH showed abnormal increase from enhanced concentration of blood after marathon becoming hyper-activation even during the recovery period. Keywords: Follicle-stimulating hormone, Luteinizing hormone, Thyroid hormones, Triiodothyronine, Running Received: October 15, 2018 Revised: November 23, 2018 Accepted: November 26, 2018 Correspondence: Young-Joo Kim Department of Exercise Rehabilitation Welfare, Sungshin University, Bomun-ro 34da-gil, Seongbuk-gu, Seoul 02844, Korea Tel: , Fax: , kyj87@sungshin.ac.kr *This work was supported by the Sungshin University research grant of Copyright 2018 The Korean Society of Sports Medicine CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 214 대한스포츠의학회지

2 신경아외. 울트라마라톤이뇌하수체전엽및갑상선호르몬에미치는영향 서론적당한운동은비만, 제 2형당뇨병, 고혈압, 심혈관질환과같은대사성질환의예방및치료에효과적인것으로알려져있다 1. 그러나과도한운동은선수들에게피로및 overtraining 증후군에의한부상을초래하며, 스트레스로인한호르몬불균형을유발하는것으로보고된다 2. 호르몬은인체에국소적으로뿐만아니라전신의자율신경계를조절하고통합하는기능을가지며, 외부자극에신속하게반응하기때문에운동상황에서중요한역할을한다 3. 급성운동은카테콜라민 (catecholamine), 성장호르몬, 글루카곤 (glucagon), 테스토스테론 (testosterone), 부신피질자극호르몬 (adrenocorticotropic hormone), 코티졸 (cortisol) 및프로락틴 (prolactin) 의생성과분비를증가시키는것으로알려져있다 4,5. 특히갑상선호르몬은거의모든조직에서산소소비를촉진하고지질과탄수화물대사조절에관여하는등대사와발달에결정적인역할을한다 6. 운동에의해갑상선자극호르몬 (thyroid stimulating hormone [TSH]) 의방출량이증가하고그에따른갑상선호르몬분비가촉진되는것으로알려져있으나 7, 장기간훈련에의한갑상선자극호르몬과갑상선호르몬변화는일관된결과를보이고있지않다 8. 또한운동에의해시상하부-뇌하수체-성선축 (hypothalamus-pituitary-gonadal axis) 의변화가나타나며, Lehmann 등 9 은지구력트레이닝에의해난포자극호르몬 (follicle-stimulating hormone [FSH]) 이증가한다고보고하였다. 그러나 Wheeler 등 10 은지구력트레이닝후에테스토스테론은감소한반면, 황체형성호르몬 (luteinizing hormone [LH]) 과 FSH 농도는변화가없다고보고하였다. 이러한호르몬과관련된지표들의생리적기능과임상적중요성에대한정의는잘확립되어있지만, 일과성및계절에따른변동성을제외한다른생물학적변수의영향에대해서는연구가부족하다 11. 운동에대한호르몬반응은운동강도, 지속기간, 운동방식, 피험자의훈련상태등여러요인에따라달라지며 12,13, 운동과호르몬변화에대한기전은아직명확하게밝혀지지않고있다. 울트라마라톤은지난 30년동안전세계적으로많은참가자들이즐기는경기로우리나라에서도마라톤동호인들의참여가증가하고있으나, 육체적한계에도달하는울트라마라톤이내분비계항상성조절에미치는영향에대해정확한결과를제시하지못하고있다. 또한뇌하수체전엽호르몬과갑상선호르몬은내분비세포활성및생체대사조절에중요한호르몬이지만, 울트라마라톤에의한영향은일관된결과를보이고 있지않다. 따라서본연구에서는극심한 100 km 울트라마라톤경기에서시작전과 100 km 완주직후의변화와함께, 완주 24시간 (1 day) 후, 완주 72시간 (3 days) 후, 완주 120시간 (5 days) 후의회복기까지뇌하수체전엽호르몬 (LH, FSH, TSH) 과갑상선호르몬 (T3, T4, Free T4) 의생리학적변화를조사하여 100 km 울트라마라톤이내분비계항상성유지에미치는영향을알아보고자하였다. 연구방법 1. 연구대상자및절차본연구의참여자격은남자 40세이상 60세이하의중년으로 100 km 울트라마라톤을 1회이상완주한경험자로하였고연구제외대상자는안정시혈압이 140/90 mm Hg인자, 심혈관질환, 당뇨, 만성신장질환및간질환을진단받은자, 고혈압약물복용자및 15시간 (100 km 대회완주제한시간 ) 이내로완주하지못한자로하였다. 대상자들은출발 2시간전, 100 km 완주직후, 24시간 (1 day), 72시간 (3 days), 120 시간 (5 days) 에채혈하였다. 본연구는인제대학교상계백병원연구윤리위원회승인을받은계획서에따라시행되었다 (NO ). 연구대상자는자발적인참여의사를밝혔고충분한설명에근거하여연구참여에동의하였다. 신체계측은운동부하검사전에실시하였으며운동부하검사는대회 1개월전부터수행하였다. 2. 운동부하검사운동부하검사는트레드밀 (Medtrack ST 55; Quinton Instrument Co., Boston, MA, USA) 을이용하여 Bruce protocol에따라시행하였다. 호흡가스분석은 Quinton metabolic cart (QMC; Quinton Instrument Co., Boston, MA, USA) 를이용하였고, mixing chamber mode로 15초간격으로시행하여최대산소섭취량 (VO 2max ), 호흡교환률 (respiratory exchange ratio) 을측정하였으며, 실시간심전도감시를위하여 12채널 Quinton stress test system (Q4500, Quinton Instrument Co.) 을이용하였다. 안정시혈압은자동혈압측정기 (Me-del 412, Quinton Instrument Co.) 를이용하여의자에앉아 5분간눈을감고안정된후 3분간격으로두번측정하여얻어진값중가장낮게측정된혈압을사용하였으며, 운동중혈압은자동혈압측정기를이용하여각운동단계 2분에측정하였다. 제 36 권제 4 호

3 KA Shin, et al. Effect of Ultramarathon on the Anterior Pituitary and Thyroid Hormones 3. 혈액채혈및분석 연구대상자는 100 km 울트라마라톤출발전, 100 km 완주후, 회복기 24시간 (1 day), 회복기 72시간 (3 days), 회복기 120시간 (5 days) 에주전정맥 (antecubital vein) 에서 CLSI Guidelines (Clinical and Laboratory Standards Institute) 지침에따라채혈을시행하였다. 뇌하수체전엽호르몬과갑상선호르몬은 SST 채혈관 (BD Vacutainer Serum Separator Tube, Franklin Lakes, NJ, USA) 에채혈후 3,400 rpm에서 15분간원심분리후혈청을분리하여 70 C deep freezer에보관하였다가분석하였다. 뇌하수체전엽호르몬인 LH, FSH, TSH 와갑상선호르몬인트리요오드티로닌 (triiodothyronine [T3]), 티록신 (thyroxine [T4]), Free thyroxine (Free T4) 는 Roche Modular Analytics E170 (Roche, Mannheim, Germany) 장비를사용하여전기화학발광면역측정법 (electrochemiluminescence immunoassay) 의원리로측정하였다. 각각의참고범위는 LH miu/ml, FSH miu/ml, TSH uiu/ml, T ng/ml, T μg/dl, Free T ng/dl이다. 각각의검사에대한변동계수 (coefficient of variation) 는 LH 3.5%, FSH 3.8%, TSH 2.5%, T3 5.5%, T4 7.5%, Free T4 5.8% 였다. 탈수에의한 plasma volume changes는헤마토크리트 (hematocrit) 와헤모글로빈 (hemoglobin) 으로계산하였으며 14, 헤마토크리트와헤모글로빈측정은 EDTA 채혈관에채혈후 Beckman Coulter LH750 (Beckman Coulter, Miami, FL, USA) 장비로측정하였다. Table 1. Characteristics of demographics and cardiorespiratory fitness in study participants (n=15) 4. 자료분석대상자의개인적인특성과마커들의분석은 IBM SPSS ver (IBM Corp., Armonk, NY, USA) 를이용하여분석하였다. 모든결과들은평균과표준편차로나타내었다. 시기별차이는 repeated measure analysis of variance로하였으며사후검증은 Bonferroni로하였다. 모든통계적유의수준은 p<0.05 수준으로하였다. 결과연구대상자들의연령, 신장, 체중및 BMI은각각평균 52.0±4.8세, 169.6±3.8 cm, 66.1±5.6 kg 그리고 22.9 kg/m 2 로나타났으며그외운동습관과운동부하검사결과들은 Table 1에나타난바와같다. LH (miu/ml) 는 pre-race, 100 km, 1 day, 3 days 그리고 5 days에서각각 4.5±1.9, 2.5±1.3, 5.4±2.6, 6.2±2.2, 5.7±1.1로나타났다. 즉 100 km는 pre-race보다유의하게감소하였고 (p<0.05), 1 day 는 100 km보다유의하게증가하였으며 (p<0.05), 3 days에서는 pre-race와 100 km보다유의하게높았고 (p<0.05) 5 days는 100 km보다유의하게높았다 (p<0.05) (Fig. 1). FSH (miu/ml) 는각각 5.8±2.2, 4.3±1.2, 4.7±1.7, 5.0±2.2, 5.8±1.9로나타났다. 즉 100 km, 1 day, 3 days는 pre-race보다유의하게감소하였으며 (p<0.05), 5 days는 100 km와 1 day보다유의하게높았다 (p<0.05) (Fig. 2). TSH (ulu/ml) 는각각 2.1±1.4, 2.6±1.6, 4.8±3.0, 4.5±2.6, 3.6±2.5로나타났다. 즉 1 day와 3 days는 pre-race와 100 km보다유의하게증가하였으며 (p<0.05), 5 days는 pre-race보다유의하게높았다 (p<0.05) Variable Mean±SD Age (yr) 52.0±4.8 Height (cm) 169.6±3.8 Weight (kg) 66.1±5.6 BMI (kg/m 2 ) 22.9±1.4 Marathon experience (mo) 126.6±59.1 No. of participated marathons 58.0±48.4 Race completion time (min) 203.0±15.8 VO 2max (ml/kg/min) 50.1±4.4 HR rest (bpm) 67.3±9.0 SBP rest (mm Hg) 119.7±8.5 DBP rest (mm Hg) 75.0±8.2 HR max (bpm) 171.1±9.4 SBP max (mm Hg) 224.7±31.1 DBP max (mm Hg) 68.8±12.4 SD: standard deviation, BMI: body mass index, HR: heart rate, SBP: systolic blood pressure, DBP: diastolic blood pressure. Fig. 1. Change of luteinizing (LH) according to distance and recovery phase in 100 km ultramarathon. Normal range, miu/ml. *Significantly different from the pre-race at p< 대한스포츠의학회지

4 신경아외. 울트라마라톤이뇌하수체전엽및갑상선호르몬에미치는영향 (Fig. 3). T3 (ng/ml) 는각각 0.9±0.1, 1.1±0.1, 0.9±0.1, 0.9±0.1, 0.9±0.1로나타났다. 즉 100 km는 pre-race보다유의하게증가하였으며 (p<0.05) 1 day, 3 days, 5 days는 100 km보다유의하게감소하였다 (p<0.05) (Fig. 4). T4 (µg/dl) 는각각 6.9±0.8, 7.8±0.9, 8.2±1.2, 8.9±1.3, 7.5±0.9로나타났다. 즉 100 km, 1 day, 3 days, 5 days는 pre-race보다유의하게증가하였고 (p<0.05), 3 days는 100 km보다증가하였으며 (p<0.05), 5 days는 3 days보다유의하게감소하였다 (p<0.05) (Fig. 5). Free T4 (ng/dl) 는각각 1.15±0.16, 1.29±0.20, 1.13±0.11, 1.18±0.16, 1.12±0.14로나타났다. 즉 100 km는 pre-race보다유의하게증가하였으며 (p <0.05), 1 day와 3 days는 100 km보다유의하게감소하였고 (p <0.05) 5 days는 100 km와 3 days보다유의하게감소하였다 (p <0.05) (Fig. 6). 고찰이연구는 100 km 장거리달리기가체내뇌하수체전엽및갑상선호르몬변화에미치는영향을확인하고자하였다. 그결과 100 km 울트라마라톤후회복기 5일동안갑상선자극호르몬의과활성화가나타났으나, 뇌하수체전엽호르몬인 LH, FSH와갑상선호르몬인 T3, T4, Free T4는참고치 Fig. 2. Change of follicle-stimulating hormone (FSH) according to distance and recovery phase in 100 km ultramarathon. Normal range, miu/ml. *Significantly different from the pre-race at p<0.05; Significantly different from the 100 km at p<0.05; Significantly different from the 1 day at p<0.05. Fig. 4. Change of triiodothyronine (T3) according to distance and recovery phase in 100 km ultramarathon. Normal range, ng/ml. *Significantly different from the pre-race at p<0.05; Significantly different from the 100 km at p<0.05. Fig. 3. Change of thyroid stimulating hormone (TSH) according to distance and recovery phase in 100 km ultramarathon. Normal range, uiu/ml. *Significantly different from the pre-race at p<0.05; Significantly different from the 100 km at p<0.05. Fig. 5. Change of thyroxine (T4) according to distance and recovery phase in 100 km ultramarathon. Normal range, μg/dl. *Significantly different from the pre-race at p<0.05; Significantly different from the 100 km at p<0.05; Significantly different from the 3 day at p<0.05. 제 36 권제 4 호

5 KA Shin, et al. Effect of Ultramarathon on the Anterior Pituitary and Thyroid Hormones Fig. 6. Change of free thyroxine (Free T4) according to distance and recovery phase in 100 km ultramarathon. Normal range, ng/dl. *Significantly different from the pre-race at p<0.05; Significantly different from the 100 km at p<0.05; Significantly different from 3 day at p<0.05. 내에서변화를보였다. 마라톤이나울트라마라톤같은극심한지구성운동에참여하는주자들은일반인보다우수한신체적능력과건강요인을갖고있음에도불구하고신체적과사용에따른심장돌연사, 저나트륨혈증, 내피기능부전에의한동맥경직도증가, 신장기능저하등신체에부정적사건들을초래할수있다고보고된다 장거리달리기에서인체의생리학적변화와관련된선행연구들은전해질대사, 근손상, 염증반응과심장지표의변화를검증한연구가대부분이다 16,18,19. 장기간지구력운동은반복된스트레스로인해내분비계호르몬활성에영향을미쳐신체대사에변화를줄수있다. 뇌하수체전엽호르몬중 LH는난소의에스트로겐과고환에서의테스토스테론형성을자극하는호르몬이다 20. 마라톤과같은장거리운동중 LH는감소하거나변화가없다는결과가보고된다 21,22. 본연구에서는 100 km에서경기전보다 1.8배감소하였으며, 회복기 1일에는경기전보다 1.2배증가하여 5일째까지경기전수준으로회복되지않았다. 그러나이러한변화는참고치내에서의변화였다. LH는성선자극호르몬방출호르몬 (gonadotropin-releasing hormone [GnRH]) 의자극에의해합성ㆍ분비되는데, 장거리마라톤에서 LH의감소는 GnRH의분비를조절하는시상하부조절중추에변화로 LH의분비횟수 (pulse frequency) 감소에따른것으로추정되고있다 20. 또한 LH는혈장유리형테스토스테론 (free testosterone) 의낮은농도와관련이있으므로 LH의늦은회복기반응을해석하는데유리형테스토스테론을측정하는것이필요하겠다 20. 또한 Kupchak 등 23 의연구에따르면 161 km trail run에서 LH와테스토스테론이감소하며, 이는시상하부-뇌하수체-부신축의억제에의한것이라고보고하였다. FSH는난소의여포를성숙시키며, 에스트로겐의분비를촉진한다 24. Lehmann 등은 9 지구성트레이닝에의해 FSH가증가한다고보고하였다. 지구력훈련에의한 FSH의상승은장기간격렬한훈련에의한생식기능저하증의보상으로설명될수있다 24. 그러나본연구결과는 FSH가경기전보다 100 km와회복기 1일, 3일에참고치내에서 1.3배감소를보였고회복기 5일에경기전수준으로회복되었다. 비록그농도의차이는크지않았으나통계적으로운동중 LH와 FSH 의감소에대해서어떤요인들이작용했는지는시상하부-뇌하수체- 부신축에대한구체적인생리학적규명이필요하겠다. 갑상선은생체항상성유지에필수적인내분비계의중요한부분이다 25. 갑상선에의해분비되는주요호르몬은 T3, T4로유리형또는결합형태로순환한다 25. 혈액중 T3와 T4의분비는시상하부에갑상샘자극호르몬분비호르몬의분비로뇌하수체전엽에서 TSH 분비에의해직접적으로조절되며, 일부말초조직에서 T4는 T3로전환된다 25. 몇몇의연구는운동에의해 T3, T4, TSH의유의한감소를보고하였다 26,27. 그러나또다른연구는운동이갑상선호르몬농도에영향을미치지않거나또는갑상선호르몬수치를증가시킨다고보고하였다 28,29. 이러한일관되지않은결과는연구방법및절차, 운동프로토콜, 연구대상의차이때문으로여겨진다 25. 본연구결과 TSH는경기전보다회복기 1일에 2.3배증가하였으며, 회복기 5일에도경기전수준으로회복되지않았다. Miller 등 7 은운동에의해 TSH의방출량이증가하고그로인해갑상선호르몬분비가촉진된다고보고하고있다. 그러나본연구결과에서 TSH는회복기 1일에유의하게증가하였으나, T3, T4, Free T4는경기직후부터증가하는것으로나타나 TSH의직접적인조절에의해갑상선호르몬분비가촉진된것으로보기는어렵다. 또한 T3, T4, Free T4의상승은참고범위내에서이루어졌으나, TSH는회복기 1일, 3일에참고치를벗어나과활성화되었다. 이는과도한지구력달리기에의한대사량항진에따른변화로생각되며, 시상하부-뇌하수체-갑상선축의잠재적억제제로코티졸이기능을하는것으로알려지고있어추가적인연구를통해기전을밝힐필요성이있겠다 25,30. 본연구는다음과같은제한점을가지고있으므로향후연구에서보완이요구된다. 첫째, 연구대상자 15명으로 100 km 울트라마라톤완주자들을대표하기에는그대표성이부족 218 대한스포츠의학회지

6 신경아외. 울트라마라톤이뇌하수체전엽및갑상선호르몬에미치는영향 하다. 둘째, 선수개인의식생활, 체력조건, 신체적, 정신적스트레스및그외의유전적특성을반영하지못하였다. 셋째, 가벼운조깅운동자와같은대조군을설정하지않아울트라마라톤주자의호르몬변화추이를비교할수없었다. 넷째, 운동후근육뿐아니라간세포의물리적인손상에대해서는알수없었다. 이런점을고려할때향후대조군과비교해울트라마라톤주자들에서의다양한생리화학적반응에차이를확인하는연구가필요하리라생각된다. 그러나본연구는 100 km 장거리울트라마라톤대회완주자들을대상으로경기시점별및회복기에호르몬변화를연구하였다는데의의가있다고하겠다. Conflict of Interest No potential conflict of interest relevant to this article was reported. Acknowledgements We would like to thank the ultramarathon runners participating in this research. References 1. Bluher M, Zimmer P. Metabolic and cardiovascular effects of physical activity, exercise and fitness in patients with type 2 diabetes. Dtsch Med Wochenschr 2010;135: Bobbert T, Mai K, Brechtel L, et al. Leptin and endocrine parameters in marathon runners. Int J Sports Med 2012;33: Geyssant A, Geelen G, Denis C, et al. Plasma vasopressin, renin activity, and aldosterone: effect of exercise and training. Eur J Appl Physiol Occup Physiol 1981;46: Galbo H. Integrated endocrine responses and exercise. In: DeGroot LJ, editor. Endocrinology. 3rd ed. Philadelphia (PA): W.B. Saunders; p Ball D. Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle. J Endocrinol 2015;224:R Melmed S, Park J, Hershman JM. Triiodothyronine induces a transferable factor which suppresses TSH secretion in cultured mouse thyrotropic tumor cells. Biochem Biophys Res Commun 1981;98: Miller PB, Forstein DA, Styles S. Effect of short-term diet and exercise on hormone levels and menses in obese, infertile women. J Reprod Med 2008;53: Weiss EP, Villareal DT, Racette SB, et al. Caloric restriction but not exercise-induced reductions in fat mass decrease plasma triiodothyronine concentrations: a randomized controlled trial. Rejuvenation Res 2008;11: Lehmann M, Dickhuth HH, Gendrisch G, et al. Trainingovertraining: a prospective, experimental study with experienced middle- and long-distance runners. Int J Sports Med 1991;12: Wheeler GD, Singh M, Pierce WD, Epling WF, Cumming DC. Endurance training decreases serum testosterone levels in men without change in luteinizing hormone pulsatile release. J Clin Endocrinol Metab 1991;72: Scharnhorst V, Valkenburg J, Vosters C, Vader H. Influence of preanalytical factors on the immulite intact parathyroid hormone assay. Clin Chem 2004;50: Tremblay MS, Copeland JL, Van Helder W. Effect of training status and exercise mode on endogenous steroid hormones in men. J Appl Physiol (1985) 2004;96: Tremblay MS, Copeland JL, Van Helder W. Influence of exercise duration on post-exercise steroid hormone responses in trained males. Eur J Appl Physiol 2005;94: Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974;37: Beutler J, Schmid E, Fischer S, Hurlimann S, Konrad C. Sudden cardiac death during a city marathon run. Anaesthesist 2015;64: Noakes T. Hyponatremia in distance runners: fluid and sodium balance during exercise. Curr Sports Med Rep 2002; 1: Vlachopoulos C, Kardara D, Anastasakis A, et al. Arterial stiffness and wave reflections in marathon runners. Am J Hypertens 2010;23: Shin KA, Park KD, Ahn J, Park Y, Kim YJ. Comparison of changes in biochemical markers for skeletal muscles, hepatic metabolism, and renal function after three types of long-distance running: observational study. Medicine (Baltimore) 2016;95:e Kim YJ, Shin YO, Lee JB, et al. The effects of running a 308 km ultra-marathon on cardiac markers. Eur J Sport Sci 2014;14 Suppl 1:S MacConnie SE, Barkan A, Lampman RM, Schork MA, Beitins IZ. Decreased hypothalamic gonadotropin-releasing hormone secretion in male marathon runners. N Engl J Med 1986;315: 제 36 권제 4 호

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전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -