Role of Socioeconomic Status and Reproductive Factors in Breast Cancer: A Case-Control Study

Rintasyövän sosioekonomiset ja lisääntymisterveyteen liittyvät vaaratekijät Intiassa Tämän tutkimuksen tarkoituksena oli selvittää sosioekonomisen aseman ja lisääntymisterveyteen liittyvien tekijöiden merkitystä rintasyövän vaaratekijöinä Intiassa. Tutkimus toteutettiin Kidwai Memorial Institute of Oncologyssa, joka on paikallinen syövänhoito- ja tutkimuslaitos Bangaloren kaupungissa Karnatakan osavaltiossa eteläisessä Intiassa. Intia on nopeasti teollistumassa ja kaupungistumassa, jonka vuoksi elämäntavat muuttuvat. Naiset menevät naimisiin vanhempina ja synnyttävät myöhemmin ja vähemmän lapsia. Heidän sosioekonominen asemansakin on paranemassa. Väestönlaskentatietojen perusteella koko Intiassa naisten keskimääräinen avioitumisikä nousi 12,5 ikävuodesta vuosina 1921-31 vuosiin 1961-71 mennessä 17,2 ikävuoteen ja vastaavasti Mumbaissa (ent. Bombay) 18,5 ikävuodesta 20,1 vuoteen vuosien 1960 ja 1965 välillä. Näiden muutosten vaikutuksesta rintasyövän ilmaantuvuus on hiljalleen suurentunut Intiassa. Vaikka rintasyövän ilmaantuvuusluvut ovat edelleen matalat Intian maaseudulla, ne ovat kaupungeissa korkeammat. Rintasyöpä on naisten yleisin syöpä Mumbaissa, Delhissä, Bangaloressa ja Bhopalissa ja toiseksi yleisin Chennaissa ja Barshissa. Rintasyövän ikävakioitu ilmaantuvuus vaihteli näissä kaupungeissa välillä 24,5-30,8 100 000 naista kohden vuosina 1997-1998. Poikkeuksena oli vain Barshi, jossa vastaava ilmaantuvuus oli vain 8,1. Vertailun vuoksi vastaava ilmaantuvuus Suomessa oli 77,0. Kidwain sairaalan syöpärekisteri kerää tiedot noin 500 rintasyöpäpotilaasta vuosittain. Tätä tapaus-verrokkitutkimusta varten kerättiin tiedot 360 histologisesti varmistetulta rintasyöpäpotilaalta ja vastaavalta määrältä iän suhteen kaltaistettuja verrokkipotilaita, jotka eivät sairastaneet rinnan, sukuelinten tai hormonaalisia sairauksia. Rintasyövän vaara kuvataan vaarasuhteina (odds ratio, OR). Tässä tiivistelmässä esitetään vain käytettävissä olevien sekoittavien tekijöiden suhteen vakioituja lukuja (monimuuttuja-analyysi käyttäen ehdollista logistista regressiomallitusta). Tuloksissa vertailuryhmän rintasyöpävaara on asetettu luvuksi yksi. Tärkeimmät tulokset olivat seuraavat: Koulutustason kohoamisen myötä rintasyövän vaara suureni: Lukutaidottomien naisten rintasyöpävaaraan verrattuna oppikoulun käyneiden naisten vaara oli noin kolminkertainen (OR 3,14) ja yliopistokoulutuksen saaneiden naisten rintasyöpävaara oli vastaavasti 2,5-kertainen (OR 2,49). Molemmat tulokset olivat tilastollisesti merkitseviä. Kun naiset jaettiin kahteen tuloluokkaan, varakkaampien naisten rintasyöpävaara oli suurempi kuin vähemmän ansaitsevien (OR 1,46). Myös kaupungeissa asuvien naisten vaara oli suurempi kuin maaseudulla asuvien naisten (OR 1,47). Kun rintasyöpävaaraa verrattiin kolmen uskonnollisen ryhmän välillä, sekä muslimien (OR 1,92) että kristittyjen vaara (OR 1,63) oli suurentunut hinduihin verrattuna. Naimattomien naisten rintasyöpävaara oli voimakkaasti suurentunut naimisissa oleviin verrattuna (OR 8,74). Synnyttämättömien naisten vaara oli suurentunut synnyttäneisiin verrattuna (OR 2,14) ja vielä enemmän suurentunut verrattuna yli kuusi lasta synnyttäneisiin naisiin (OR 2,96). Yli 30-vuotiaiden ensisynnyttäjien rintasyöpävaara oli suurentunut (OR 2,32) samoin kuin 20-24-vuotiaiden ensisynnyttäjienkin vaara (OR 1,67) verrattuna alle 20-vuotiaana synnyttäneisiin. Jos nainen ei ollut koskaan imettänyt, rintasyöpävaara oli suurentunut imettäneisiin naisiin verrattuna (OR 1,75). Pitkään imettämisellä vaikutti olevan suojavaikutusta, joka ei riippunut muista sekoittavista tekijöistä. Alle kuusi kuukautta imettäneiden naisten rintasyöpävaara oli suurentunut yli 18 kuukautta imettäneisiin naisiin verrattuna (OR 8,59). Tässä tutkimuksessa imettäminen näytti suurelta osalta selittävän lapsilukuun liittyvät vaarasuhteiden erot. Vaihdevuodet ohittaneiden naisten rintasyöpävaara oli suurentunut verrattuna naisiin, joilla vielä oli kuukautiset (OR 1,58). Kuukautisten alkamisiällä, iällä viimeisen synnytyksen aikaan ja vaihdevuosi-iällä ei näyttänyt olevan merkitystä rintasyöpävaaran suhteen tässä tutkimuksessa. Tässä aineistossa sukulaisella esiintynyt rintasyöpä oli harvinainen.Breast cancer is predominantly a disease of women and has a major impact on the health of women. Globally breast cancer is the most frequent cancer among women accounting for 21% of all cancers in women and ranking third (9.8%) overall when both sexes were considered together (Parkin et al. 1999). It is the most common cancer among women in all the developed areas (except for Japan, where it ranks third), as well as in Northern Africa, South America, East, Southeast and Western Asia and Micronesia/Polynesia. The incidence rates of breast cancer are high in North America and Northern Europe, intermediate in southern Europe and South America and low in Asia and Africa. The age-standardized incidence rates of breast cancer per 100,000 women were over 100 in Montevideo, Uruguay in South America (114.9), among Non-Hispanic Whites in California, North America (109.6) and among Hawaiians, Hawaii in Oceania (101.3). The rate (age-standardized) of breast cancer in Finland was 72.4 per 100,000 women. The lowest incidence rate of breast cancer was seen in The Gambia in Africa (Parkin et al. 2002). Approximately 183,000 women (about 32% of all incident cancers in women) are diagnosed with invasive breast cancer each year in America and nearly 41,000 women die of the disease. In American women, breast cancer is the most frequently diagnosed cancer and second leading cause of cancer death, second only to lung cancer. In women aged 40 to 55, breast cancer is the leading cause of all mortality. However, there has been a slight decline in breast cancer mortality overall, which can be attributed both to the success of early detection programmes and to advances in treatment, particularly development in systemic therapy (Winer et al. 2001). Researchers have postulated that changes in the age of childbearing, alterations in the average ages of menopause and menarche, and/or the widespread use of oral contraceptives and hormone replacement therapy have contributed to the increasing incidence (Honig 1998). Although screening has become widely available, a relatively small percentage of the population takes advantage of it; only 15% of women over 50 years of age in North America were estimated to have had a mammogram in 1984. The risk of developing breast cancer is age related. Breast cancer is uncommon before age 40; only 6.5% of all cases were diagnosed before age 39 (Miller et al. 1994). The risk increases sharply at age 40 and then continues to increase with a median age of breast cancer diagnosis of 64 years (Honig 1998). India is rapidly stepping towards industrialization vis a vis urbanization resulting in a change of life style factors, particularly an increase in age at marriage, delay in age at first birth, reduction in parity, improved socioeconomic conditions etc. Estimates compiled from decennial census surveys indicate that for the whole of India age at marriage increased, on average, from 12.5 years (over the period 1921 31) to 17.2 years (over the period 1961 71). The mean age at marriage in greater Bombay (now Mumbai) for women was 18.5 years in 1960 and 20.1 years in 1965 (Jayant 1986). All these factors have possibly contributed to the gradual increase in the incidence of breast cancer in India. Even though the rates of breast cancer were low in rural areas of India, the rates are higher in urban areas. Breast cancer is the leading site of cancer among women in Bombay (now Mumbai), Delhi, Bangalore and Bhopal and it ranks second at Madras (now Chennai) and Barshi. The age-adjusted rates of breast cancer in these centres were 30.8, 30.8, 25.2, 24.5, 26.7 and 8.1 per 100,000 women respectively during the period 1997 98. (NCRP 2002a). The present study was undertaken in a southern State of India at Kidwai Memorial Institute of Oncology (A Regional Centre for Cancer Research and Treatment), Bangalore, Karnataka with an objective to study the socioeconomic status and reproductive factors associated with the risk of breast cancer. Summary The incidence rates of breast cancer among females are showing a rising trend in all the urban registries of India. Breast cancer is the first leading site of cancer in 4 out of the 5 urban registries Bangalore, Mumbai (Bombay), Delhi and Bhopal. In Chennai (Madras) it is the second leading site of cancer but a tendency of breast cancer to rise over time has been observed. In the hospital based cancer registry at Kidwai Memorial Institute of Oncology (A Regional Center for Cancer Research and Treatment) about 500 cases of breast cancer are registered annually. In order to study the role of socioeconomic status vis a vis standard of living, reproductive factors and risk of breast cancer a hospital-based case control study was undertaken. 360 cases of breast cancer confirmed microscopically (excluding cases with prior history of treatment, those too advanced for treatment, non-microscopic confirmation, dropouts before diagnosis and in-situ carcinomas) and an equal number of controls without a history of any disease in the breast, gynecological organs or endocrine glands matched for age (plus or minus 5 years in the WHO age group) formed the subjects of the study. The results are reported based on univariate (unadjusted) and multivariate (conditional logistic regression model) odds ratios after adjusting for socioeconomic, reproductive and other risk factors. The major findings of the study are: The risk of breast cancer increased as the level of education increased. Compared to illiterate women (no schooling) women with secondary education (up to 10 years of schooling) had a significantly more than three- fold risk (adj. OR 3.14, unadj. OR 4.09) and women with an educational level of college and above (11 15 or more years of schooling) had a two and a half-fold (adj. OR 2.49, unadj. OR 4.15) significant risk of developing breast cancer. Women with higher income are at an elevated risk (adj. OR 1.46, unadj. OR 3.06) compared with women with lower income. Compared to women living in rural areas, women living in urban areas appeared to be at increased risk. (adj. OR 1.47, unadj. OR 2.05) Among the three major religions Hinduism, Islam and Christianity Muslims were found to be at an elevated risk (adj. OR 1.92; unadj. OR 1.67) of developing breast cancer (significant) followed by Christians (adj. OR 1.63, unadj. OR 2.60) compared with Hindus. Compared with ever-married women, never-married women are at increased risk (adj. OR 8.74, unadj. OR 10.00) of developing breast cancer. Nulliparous women had a two-fold risk (adj. OR 2.14, unadj. OR 1.31) of developing breast cancer compared with parous women. Compared with parous women with more than six children, the risk among nulliparous women was found to be about three-fold (adj. OR 2.96, unadj. OR 2.14). Women who delayed their first childbirth were at elevated risk of developing breast cancer. Compared with women whose age at first child- birth was below 20 years, women whose age at first childbirth was above 30 years were at more than two-fold risk (adj. OR 2.32, unadj. OR 4.75) and women whose age at first childbirth was between 20 24 years were at almost two-fold risk (adj. OR 1.67, unadj. OR 1.89) of developing breast cancer. The risk of developing breast cancer was found to be high in women who had never lactated (adj. OR 1.75, unadj. OR 1.75) compared with ever lactated. Breastfeeding for a longer duration emerged as an apparent protective factor for the risk of breast cancer independent of age at first birth, parity and other potential confounding factors. Compared with women who breastfed for more than 18 months women who breastfed for less than 6 months are at significantly more than eight-fold risk (adj. OR 8.59, unadj. OR 11.26). Ultimately it may be that breastfeeding accounted for much of the effect due to parity in this study. This is what relatively consistent in other studies as well. Postmenopausal women are at an elevated risk compared to pre- menopausal women (adj. OR 1.58, unadj. OR 1.41). Age at menarche, parity, age at last birth and age at menopause appear to have no association with the risk of breast cancer in the present study. Family history was rare in this material and most of the effects could be accounted for by socioeconomic status, hence genetic inheritance in the aetiology of breast cancer appears to be not of importance in India, at least given the current distribution of risk factors. This may change if the environment changes and gene expression changes