Effect modification of smoking status and menopausal status on the association between die- tary intake of acrylamide and risk of breast cancer

Introduction Acrylamide is a probable human carcinogen 1 that occurs natu- rally in starchy foods during cooking processes at high tempera- tures 2. Aside from occupational exposures and smoking 3, main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee 4 5. High acrylamide intake has been associated with altered sex-steroid hormone concen- trations and increased risk of hormone-dependent cancers, such breast neoplasm with inconsistent findings 6-9. Since this cancer type represent a major cause of death among both premenopau- sal and postmenopausal women 10, investigating its environmen- tal and life-style risk factors, including for instance acrylamide intake, is of key relevance under a public health perspective. Materials and methods We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast cancer. Using PubMed, we performed a systematic search for non-experimental studies published through October 20, 2019 and we first performed a meta-analysis of the overall measure of association. Subsequently, we carried out a dose-response meta- analysis of these associations using restricted cubic spline models which allow to estimate the summary relative risk (sRR) across a large exposure range of acrylamide intake alongside with their approximate pointwise 95% confidence interval (CI) 11 12. Results We identified 10 papers covering 8 different study populations: 9 cohorts and 1 case-control studies, with a total of 18100 cases of breast cancer. Acrylamide dietary intake ranged from 3.6 μg/ day to 44 μg/day, with both mean and median values of 21 μg/ day (range 6.3 to 29.8 μg/day). In the meta-analysis summarizing the RR in the highest category of exposure versus the lowest, we found no evidence of cancer risk at any levels of acrylamide ex- posure. After restricting the analysis to never smokers, we found similar results, if not a reverse correlation. In analyses stratified by menopausal status, we found no appreciable association be- tween exposure and risk of breast cancer among premenopau- sal women, and an inverse association in postmenopausal par- ticipants. Results among never-smoking premenopausal women was available only for one study, which reported a positive as- sociation between acrylamide intake and breast cancer risk. Con- versely, among postmenopausal women, we found no associa- tion for breast cancer in never-smokers. In the dose-response me- ta-analysis, we found evidence of a null or even inverse relation between exposure to dietary acrylamide and breast cancer risk, particularly in never smokers and in post-menopausal women. Interestingly, in subgroup analysis limited to pre-menopausal women, breast cancer risk linearly increased starting from 20 μg/ day of acrylamide intake. Conclusions In conclusion, there was limited evidence for an association between acrylamide intake and breast cancer risk, with the ex- ception of increased risks at the highest levels of acrylamide exposure among premenopausal women, which warrants further investigation.