乳腺癌的分子生物学进展(1)

• Breast cancer occurring before age 50 (premenopausal) in first- or second-degree relative(s) • Two or more first- or second-degree relatives with breast or ovarian cancer • One or more first-, second-, or third-degree relative(s) with breast and ovarian cancer or with two separate or independent breast cancers • Male relative(s) with breast cancer • One or more first-, second-, or third-degree relative(s) with BRCA1 and/or BRCA2 gene mutation Note. First-degree relatives are mother, daughter, sister, father, son, and brother. Second-degree relatives are grandmother, aunt, niece, grandfather, uncle, and nephew. Third-degree relatives are greatgrandmother, great-grandfather, great-aunt, great-uncle, and female and male first cousins. Figure 1. Family History That Increases Breast Cancer Risk
Part 1 Epidemiology
Study of cancer patterns in populations, cancer epidemiology, can contribute substantially to knowledge about the origins of cancer.
Factor 5: Nulliparity and older age at first live birth Women with a first full-term pregnancy at younger than full20 years of age have half the risk of nulliparous women or women over the age of 35 at their first birth. Interestingly, women with their first birth after age of 35 are even at higher risk than nulliparous women.
Epidemiology
Factor 2: Age Breast cancer is rarely found before the age of 25 years except in certain familial cases. The incidence rises throughout a woman's lifetime. Seventy-seven per cent of cases occur in women over 50 years of age. The average age at diagnosis is 64 years.
Factor 6: Family history of breast cancer Women with one, two, and three or more firstdegree affected relatives have an increased breast cancer risk when compared with women who do not have an affected relative (risk ratios 1.8, 2.9 and 3.9, respectively)
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Breast cancer risk factors
WellWell-confirmed factors Probable factors
Factor 1: Geographic location
low-risk: Far East, Africa and South America lowhighhigh-risk: North America and Northern Europe areas.
Hereditary Breast Cancer
About 25% of familial breast cancers (or around 3% of all breast cancers) can be attributed to two highly penetrant autosomal dominant genes: BRCA1 and BRCA2. About 10% of familial breast cancers are attributed to p53, PTEN, CHEK2, ATM genes.
Epidemiology
(Adapted from Jemal A, et al: Cancer statistics, 2003. CA Cancer J Clin 53:5, 2003.)
WHO 2007
Worldwide, the most common malignant tumors in males are cancers of lung, stomach, liver, colon/rectum and esophagus. Worldwide, the most common malignant tumors in females are cancers of breast, lung, stomach, colon/rectum and cervix.
Figure: Initiation and promotion of a neoplasm. Polycyclic hydrocarbons (多环烃), which are carcinogens at high doses, cause skin cancer. The action of polycyclic hydrocarbons is enhanced by croton oil (巴豆油), which acts as a promoter. This is best seen by the effect of croton oil in producing cancer when a subcarcinogenic (low) dose of polycyclic hydrocarbon is used. Note that croton oil in any dose does not cause cancer. Many carcinogens act as both initiators and promoters Adapted from Kumar: Robbins and Cotran: Pathologic Basis of Disease
Breast carcinoma
Breast carcinoma is the most common malignancy in women. A woman who lives to age 90 has a one in eight chance of developing breast cancer.
One mechanism may involve a markedly reduced susceptibility of the fully mammary gland to carcinogens, due to in part a decrease in proliferative activity of parous (经产的) epithelium. (经产的) Another possibility is due to the altered hormonal environment during pregnancy (e.g. decrease in circulating growth factor hormone etc).
Factor 3: Early Age of Menarche Women who reach menarche when younger than 12 years of age have a 20% increased risk compared to women who reach menarche when more than 14 years of age. It is probably because of a prolonged exposure of breast epithelium to estrogens and progesterone due to earlier regular ovulatory menstrual cycles.
Breast carcinomas
Cancer and cardiovascular diseases are the leading causes of death around the world. Cancers arising in tissues such as stomach, liver, lung, breast, nasopharynx and bone marrow are very common in China.
Factor 4: Late Age of Menopause Late menopause (>54) also increases risk, but the magnitude of the risk has not been quantified. In contrast, surgically-induced menopause surgically(ovariectomy or hysterectomy) before the age of 35 results in a decrease of breast cancer risk. Even unilateral ovariectomy performed before the age of 45 has been demonstrated to be protective.