Our study provides an evidence-based, consistent assessment of numbers of cancer deaths and cases in China in the year 2005, which could be attributable to reproductive factors and exogenous hormone (OCs and HRT). Compared with counterfactual exposure distribution, there was 8.4% attributable to reduced duration of breastfeeding, 6% to nulliparity and 4.6% to decreased number of children for breast cancer, and 12.4% for ovarian cancer in 2001. Greatly influenced by government policy and economic development, reproduction behavior in China has significantly changed in recent decades. Therefore, RF changes over 20 years contribute to approximately 7% of breast cancer occurrence and mortality. The estimated overall prevalence of HRT and OC use in 2005 was 6.72% and 1.74%, respectively, with about 0.2% of breast cancer cases and deaths attributable to each agent usage. OC and HRT use account for a very small fraction of the burden of breast cancer due to the unpopularity of their use.
For sensitivity analysis, we used PAF change due to RF change estimated between 1982 and 2001 to calculate changes in cancer incidence and mortality. There is a considerable difference between sample sizes of the prevalence data of RFs collected in 1982 and 2001. In 1982, a large survey regarding fertility and reproduction was conducted involving 60% of the Chinese female population at that time. About 297 million women were surveyed in order to determine the prevalence of several important RFs including parity data in China. However, despite a growing population in 2001, the national survey on family planning and reproduction health in 2001 only sampled 39,586 women, a number which is ten thousand times less than the number surveyed in 1982. Since both studies were based on representative samples of the population and response rates were high, incomparability between datasets due to sample size difference can be minimized. It is worth noting that current prevalence data for PAF calculation was limited to women aged 15-49 years, but most breast cancer cases occur after 40 years old and among women not at parous age. The same concern applies to ovarian cancer. Since there is lack of reproductive data among women in wider age ranges, the overall percentage of breast cancer cases or deaths attributable to RF change might be underestimated. Thus, there is a significant need for large surveys structured to include older women to represent reproduction status for the entire population.
Family planning policy began to be implemented in China in late 1970s. As a result of this policy, though the percentage of parous women has been increasing over the years, there has been a decreasing trend in the number of children averaged per woman or parous woman, as seen by our collected data from 1982 to 2004 (data not shown). Consequently, this significant decrease contributes the greatest change in PAF (29.5%) for breast cancer in the sensitivity analysis. Correspondingly, PAF change due to the decreasing mean number of children per woman for ovarian cancer also accounted for 13.2%. Furthermore, recent data has shown an even lower mean number of children per parous woman or woman, which might contribute to greater PAF change and more cancer cases or deaths attributable after 2001. On the other hand, when comparing the 2001 data with ideal exposure, the exposure difference shrank, and the PAF to breast cancer was only 4.6%. PAF to ovarian cancer, however, remained close to the result of the sensitivity analysis.
The effect of family planning policy on reproduction in China was also seen in regard to age at first birth. Recommendations by the government on late marriage and birth have allowed more women to choose to have their first child at a time of their own choice. Taking into account the strides in education and career development, more and more women, especially from urban areas, have decided to delay having children to a later time in their lives. The percentage of age at first birth greater than or equal to 30 years old has, as expected, been on the increase over the past several years. PAF change for breast cancer due to this factor is, however, not as significant as due to parity for breast cancer. However, a comparison of the 2001 data, with its small sample size (1,008 women), against the 1982 data, which surveyed 191,629 women, might yield conservative estimates, since other source data from around 2005 suggest a bigger proportion of women having their first birth after 30 years old. In accordance with delayed age at first birth among Chinese women, the number of breastfeeding months was also reduced. Further- more, as we used 15 months to roughly estimate the mean number of months of pure breastfeeding longer than 8 months (see method section), it is possible that the duration of breastfeeding is conservatively estimated at each time point. More studies should be conducted to provide more accurate estimates on duration of breastfeeding.
found that OC use is associated with different levels of risk for breast cancer in younger and older women. However, most studies use 40- or 45-year old women as a parameter to separate younger and older age groups, while our data surveyed women from 15 to 49 years old in China. PAF calculation in our study assumes the same risk for different age groups. We found more women aged 15-19 years use OC for contraception, whereas only about 2% of women 20 years old or older rely on OC for birth control. It is logical that younger women, especially when they have not yet had a child, would choose to use OC, while older women most commonly tend to undergo tubal ligation or use an intrauterine device (IUD) for birth control. Overall, PAF increase in breast cancer due to OC use is very low, as are cancer cases and deaths attributable to OC use. This is largely because of the very low prevalence of OC use in China.
Our study showed that HRT prevalence is lower than in Europe and North America. The prevalence of HRT use in China is 6.7% (excluding women for whom there was no information on the duration of using HRT), compared with 20.7% in the USA in 1995
, 18.4% in Denmark in 1997
and 19% in the UK in 1990
. The major reason might be that the majority of Chinese perimenopausal women did not have enough knowledge about the perimenopause syndrome. Less than 20% of perimenopausal women seek advice on perimenopause syndrome from their gynecologist
. The percentage of perimenopausal women aware of HRT was as low as 7.9%
. The data makes clear that not all Chinese women select HRT, regardless of the presence of symptoms, while only a small number of women take HRT because of serious symptoms. Also, most perimenopausal women in China often discontinue HRT after their symptoms have been effectively brought under control
. That explained the reason that the prevalence of HRT use for over 5 years is very low in China. This led to the total PAF of breast cancer attributable to HRT in China of 0.31%, clearly lower than that reported in developed countries such as France (0.4% for ERT users and 18.8% for ERT and EPRT users)
Bernstein reviewed that many other RFs, such as early age at menarche or late age at menopause, are identified as risk factors for breast cancer
and that tubal ligation protects against ovarian cancer
. These RFs were not studied in this paper, but they might have effect on cancer incidence and mortality as well. Other risk factors of breast cancer and ovarian cancer include family history, obesity, dietary factor, cigarette smoking, alcohol drinking and genetics[7, 10, 55].
Also, the time interval we chose in the sensitivity analysis is relatively short since long-term change in cancer incidence and mortality due to RF change is more obvious. The shortage of data, especially before 1980, can not allow for a longer-term interval. Nevertheless, prevalence data of RFs and OC use are from national surveys and based on relatively big sample size, which guaranteed good data quality. Prevalence data of HRT use and RR estimates for RFs and OC use were from either meta-analyses results or literature based on a representative sample in China. This ensured good data used and robust conclusions made in this study. The value of our study is that we used national data instead of local data in PAF calculation, which could be applied to general population.
As the study on PAF of breast and ovarian cancer to RFs, OCs and HRT in China, our report provides an estimation of the number and percentage of cancer cases and deaths attributable to these factors, which may serve as a basis for future research in cancer prevention and control. It suggests that in the process of implementing family planning policy, health considerations should be taken into account and related health programs might be offered for disease prevention and control.