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Indicator Number of oral contraceptive users among Relative risk (95% confidence interval) androgen receptor with a four times higher affinity than testosterone [18]. One determinant of intra-prostatic dihydrotestosterone formation may be variation in the activity of intraprostatic (type II) 5-α-reductase (SRD5A2), that catalyses the testosterone-dihydrotestosterone conversion. Another possible determinant, which could provide a physiological link between prostate cancer risk and nutritional lifestyle factors, is an increase in circulating levels of bioavailable testosterone unbound to sex hormone binding globulin, that can freely diffuse into the prostatic cells. The androgen hypothesis originated from 80 The causes of cancer Ovarian cancer cases Controls Age (years) < 45 48 221 0.6 (0.3-1.0) 45-54 30 92 0.5 (0.3-1.0) 55-64 2 11 0.6 (0.4-0.9) Parity 0 21 67 0.6 (0.4-0.8) 1 15 75 0.6 (0.4-0.9) ≥ 2 44 182 0.3 (0.1-1.4) Table 2.22 Estimated relative risk of ovarian cancer for women who have used oral contraceptives at any period in their lives, given for different ages and number of births. S. Franceschi et al. (1991) Int J Cancer, 49: 61-65. observations that surgical or medical castration can often dramatically improve the clinical course of advanced metastatic prostate cancer patients. Furthermore, Japanese and Chinese migrants to the USA have lower incidence rates of prostate cancer than men of African or European ancestry, and at the same time have been found to have lower 5-α-reductase activity; there are positive associations of prostate cancer risk with specific genetic polymorphisms in the SRD5A2 gene. Finally, polymorphisms in the androgen receptor gene causing increased receptor transactivation have also been found associated with an increase in prostate cancer risk [12,19]. On the basis of the above observations, one can predict an increase in prostate cancer risk in men with elevated blood levels of bioavailable testosterone, as well as with levels of androstanediol-glucuronide, a major breakdown product of dihydrotestosterone and a possible marker of intraprostatic androgen activity. These predictions, however, have received only very limited support from epidemiological studies [20]. There is little evidence as yet for any association between circulating estrogen levels and prostate cancer risk.
REFERENCES 1. Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev, 15: 36-47. 2. Weiss NS, Cook LS, Farrow DC, Rosenblatt KA (1996) Ovarian cancer. In: Schottenfeld D, Fraumeni JF, eds, Cancer Epidemiology and Prevention, New York, Oxford University Press, 1040-1057. 3. Secreto G, Zumoff B (1994) Abnormal production of androgens in women with breast cancer. Anticancer Res, 14: 2113-2117. 4. Thomas HV, Reeves GK, Key TJ (1997) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control, 8: 922-928. 5. Thomas HV, Key TJ, Allen DS, Moore JW, Dowsett M, Fentiman IS, Wang DY (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer, 76: 401-405. 6. Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW (1994) A prospective study of endogenous hormones and breast cancer. Cancer Detect Prev, 18: 79-85. 7. Rosenberg CR, Pasternack BS, Shore RE, Koenig KL, Toniolo PG (1994) Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle. Am J Epidemiol, 140: 518-525. 8. IARC (1998) Hormonal Contraception and Post- Menopausal Hormonal Therapy (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 72), Lyon, IARCPress. 9. Moreno V, Bosch FX, Muñoz N, Meijer CJLM, Shah KV, Walboomers JMM, Herrero R, Franceschi S (2002) Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multi-centric case-control study. Lancet, 359: 1085-1092. 10. Ross RK, Paganini-Hill A, Wan PC, Pike MC (2000) Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst, 92: 328-332. 11. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA, 283: 485-491. 12. Bosland MC (2000) The role of steroid hormones in prostate carcinogenesis. J Natl Cancer Inst Monogr, 39-66. 13. Grady D, Ernster VL (1996) Endometrial cancer. In: Schottenfeld D, Fraumeni JF, eds, Cancer Epidemiology and Prevention, New York, Oxford University Press, 1058-1089. 14. Key TJ, Pike MC (1988) The dose-effect relationship between “unopposed” oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer, 57: 205-212. 15. Bernstein L, Ross RK (1993) Endogenous hormones and breast cancer risk. Epidemiol Rev, 15: 48-65. 16. Cramer DW, Welch WR (1983) Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst, 71: 717-721. 17. Fathalla MF (1971) Incessant ovulation -- a factor in ovarian neoplasia? Lancet, 2: 163. 18. Bosland MC (1996) Hormonal factors in carcinogenesis of the prostate and testis in humans and in animal models. Prog Clin Biol Res, 394: 309-352. 19. Ross RK, Pike MC, Coetzee GA, Reichardt JK, Yu MC, Feigelson H, Stanczyk FZ, Kolonel LN, Henderson BE (1998) Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res, 58: 4497-4504. 20. Eaton NE, Reeves GK, Appleby PN, Key TJ (1999) Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. Br J Cancer, 80: 930- 934. WEBSITE The Endocrine Society: http://www.endo-society.org/about/index.cfm Reproductive factors and hormones 81
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WORLD HEALTH ORGANIZATION WHO OMS I
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WORLD CANCER REPORT Editors Bernard
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CONTENTS Foreword 9 1 The global bu
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The global burden of cancer Cancer
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Fig. 1.2 Incidence and mortality of
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Central and Southern Europe differ
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Incidence of cancer in South Centra
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from documentation of disease to a
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TOBACCO SUMMARY >In addition to lun
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Fig. 2.3 Smoking by children is inc
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Cancers positively Sex Standardized
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PHARMACOLOGICAL APPROACHES TO SMOKI
Page 26 and 27: level the dose—response relations
Page 28 and 29: lipoprotein-associated cholesterol,
Page 30 and 31: Agent Cancer site/cancer Main indus
Page 32 and 33: Industry, occupation Cancer site/ca
Page 34 and 35: to occupational exposures in develo
Page 36 and 37: Air pollutant WHO Air Quality Guide
Page 38 and 39: der cancer of the order of 50% is p
Page 40 and 41: AFLATOXIN B 1 HEPATITIS VIRUS (chro
Page 42 and 43: Fig. 2.30 Correlation between regio
Page 44 and 45: MEDICINAL DRUGS SUMMARY > Certain d
Page 46 and 47: Drug or drug combination Cancer IAR
Page 48 and 49: Agent or substance Cancer site/canc
Page 50 and 51: sources of electromagnetic fields [
Page 52 and 53: CHRONIC INFECTIONS SUMMARY > Infect
Page 54 and 55: Infection Subclinical Mutagenic fac
Page 56 and 57: TUMOURS ASSOCIATED WITH HIV/AIDS Ap
Page 58 and 59: DIET AND NUTRITION SUMMARY > Up to
Page 60 and 61: Fig. 2.54 The age-adjusted mortalit
Page 62 and 63: OVERWEIGHT, OBESITY AND PHYSICAL AC
Page 64 and 65: IMMUNOSUPPRESSION SUMMARY >Persiste
Page 66 and 67: Fig. 2.64 Cancer following immunosu
Page 68 and 69: Syndrome Gene Location Cancer site/
Page 70 and 71: viduals, confirmation of a gene def
Page 72 and 73: REPRODUCTIVE FACTORS AND HORMONES S
Page 74 and 75: PHYTO-ESTROGENS AND CANCER PEVENTIO
Page 79 and 80: Mechanisms of tumour development Th
Page 81 and 82: The stages in tumorigenesis have be
Page 83 and 84: PRECURSOR LESIONS IN CHEMOPREVENTIO
Page 85 and 86: CARCINOGEN ACTIVATION AND DNA REPAI
Page 87 and 88: adducts, a few weeks or months for
Page 89 and 90: I Reactive oxygen species Methylati
Page 91 and 92: which remove the mismatched bases,
Page 93 and 94: Common human oncogenes Many common
Page 95 and 96: product of the RB1 gene (pRb) and a
Page 97 and 98: ates a molecular bridge between p53
Page 99 and 100: potential cancer genes altered thro
Page 101 and 102: One of the earliest genes to be ide
Page 103 and 104: Regulation of the cell cycle and co
Page 105 and 106: CELL-CELL COMMUNICATION SUMMARY > C
Page 107 and 108: Connexin genes and tumour suppressi
Page 109 and 110: APOPTOSIS SUMMARY > The term apopto
Page 111 and 112: Caspase-8 Caspase-3 c-FLIP Procaspa
Page 113 and 114: ways. Several options are under inv
Page 115 and 116: INVASION AND METASTASIS SUMMARY > T
Page 117 and 118: laminin, entactin and also heparan
Page 119 and 120: Target Example of agent Comments Ad
Page 121 and 122: organs, and to respond to local gro
Page 123 and 124: TOBACCO CONTROL SUMMARY > Tobacco-i
Page 125 and 126: Region Deaths due to % of total dea
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ipated, is primarily attributable t
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smoke. This may be achieved in part
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there is no evidence for the effica
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industries, processes and occupatio
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stoves arises in rural areas of dev
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Climbing plants on trellis at end r
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HEPATITIS B VACCINATION SUMMARY > P
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Fig. 4.17 Chronic active HBV-associ
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HUMAN PAPILLOMAVIRUS VACCINATION SU
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Vaccine Site of trial Number of pat
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prolonged use. Similar drugs, that
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aspirin and other non-steroidal ant
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SCREENING FOR BREAST CANCER SUMMARY
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Fig. 4.35 Cumulative mortality from
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SCREENING FOR PROSTATE CANCER SUMMA
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Fig. 4.39 Poster designed for an an
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is around 10% for cancer (out of ev
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45 with one positive rehydrated FOB
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eing based on (i) time trends in th
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Fig. 4.48 Women at a clinic in Indi
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SCREENING FOR ORAL CANCER SUMMARY >
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India will provide useful informati
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cer incidence following cure of inf
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100 50 25 10 5 2.5 1 Japan Males Fe
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Human cancers by organ site Maligna
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tobacco smoking: age at start, aver
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diagnosis is usually confirmed by h
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is frequent and survival rates are
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Fig. 5.14 Physician reading digital
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Markers of prognosis in breast canc
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cer in the contralateral breast (Ch
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100 50 25 10 5 2.5 1 Japan Chile Po
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depends on staging. Small intramuco
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Fig. 5.30 A diet rich in fresh frui
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ane protein involved in cell adhesi
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LIVER CANCER SUMMARY > About 560,00
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Fig. 5.39 A woman in the Gambia pre
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REFERENCES 1. Ferlay J, Bray F, Par
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Certain Possible Uncertain Age Andr
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Management The dramatic division be
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TUMOUR NORMAL Gastrula PGC 2n Impri
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CANCERS OF THE FEMALE REPRODUCTIVE
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Fig. 5.62 Five-year relative surviv
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Inheritance of high-penetrance gene
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invasive malignant. Malignant germ
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OESOPHAGEAL CANCER SUMMARY >Cancer
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Fig. 5.76 A radiographic view of an
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with a stent; laser recannulation,
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Fig. 5.82 Risk of bladder cancer am
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Partial cystectomy is appropriate f
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poorly known since hypopharyngeal c
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Fig. 5.92 Oral leukoplakia with mil
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LYMPHOMA SUMMARY > Malignant lympho
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T Fig. 5.101 Nuclear magnetic reson
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Fig. 5.106 Five-year relative survi
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Fig. 5.109 The immediate aftermath
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A B Fig. 5.113 Acute myeloid leukae
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Fig. 5.118 Five-year relative survi
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Fig. 5.120 Age-specific incidence a
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Hereditary condition Mode of inheri
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MELANOMA SUMMARY > Approximately 13
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Fig. 5.131 Primary melanoma with a
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THYROID CANCER SUMMARY > Cancer of
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Papillary carcinoma RET/PTC TRK BRA
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KIDNEY CANCER SUMMARY > Cancer of t
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Stage Clear cell carcinoma Papillar
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TUMOURS OF THE NERVOUS SYSTEM SUMMA
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ing the optic tract, brain stem and
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mut = mutant p53 wt = wildtype p53
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SURGICAL ONCOLOGY SUMMARY > Surgica
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Year Radical mastectomy (%) Modifie
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TELEMEDICINE The prospects for tele
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Equipment Energy 50% depth dose App
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CANCER EDUCATION IN MEDICAL COURSES
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Fig. 6.10 Crystals of cisplatin: mo
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Responsiveness Cancer (in decreasin
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Most of the world’s most common c
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treatment of cancer. The problems l
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duction. It is clear that tumour ce
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REHABILITATION SUMMARY > Rehabilita
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cer and its associated disability.
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REFERENCES 1. Garden FH, Gillis TA
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Cancer pain relief varies and in so
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EMERGING ISSUES IN PALLIATIVE CARE
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Cancer control The negative impact
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priority to cancer control activiti
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Prevention of cancer Every country
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- Assessing the magnitude of the ca
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high-risk women. Further details on
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ecords departments are either rudim
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THE INTERNATIONAL AGENCY FOR RESEAR
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in the capitals/urban areas of four
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in the overall cancer strategy. WHO
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68% 1955 1975 1995 2025 32% 40% by
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Fig. 7.15 A grandfather at work in
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Fig. 7.17 Main causes of death in d
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Contributors and Reviewers Sources
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Dr Vera Luiz da Costa e Silva Tobac
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Georgia Moore Centers for Disease C
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REVIEWERS Dr Sandra E. Brooks 405 W
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2.53 T. Norat and E. Riboli, IARC 2
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Gastroenterology, 118(2 Suppl 1): S
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5.106 & 5.107 IARC/SEER/Osaka Cance
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4.17 R. Lambert, IARC/Adapted from
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Brain cancer, see nervous system tu
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Fibroblast growth factor (FGF), 117
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Microarray, 240 Micronutrients, 65,
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S Saccharin, 64, 85 Salicin, 153 Sa
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