Familial risk of early and late onset cancer: nationwide prospective cohort study
BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e8076 (Published 20 December 2012) Cite this as: BMJ 2012;345:e8076
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I would like to praise the authors of the study on the familial risk of early and late onset cancer.1 It is well demonstrated that the highest familial risk of colorectal cancer is seen in the offspring of parents who were diagnosed of the same cancer at an early age. I would also like to add that there is a definite need to identify those at high risk, in order to establish an early diagnosis, to hopefully go some way in improving prognosis and reducing mortality.
Yet how to achieve this is not necessarily clear. Turning now specifically to colorectal cancer, the incidence of which has increased over the last three decades amongst young adults.2 There seems to be two pertinent factors. Firstly, as colorectal surgeons we see more young adults who have been reluctant to seek medical help often waiting for months before presenting to their general practitioner. Consequently, young adults are likely to present at stage III or IV at the time of the diagnosis. In comparison, patients 50 years or older typically present at an earlier stage, possibly due to greater health awareness.3 Secondly, younger adults have poorer prognosis due to a higher incidence of poorly differentiated mucinous carcinoma, which is characterized by rapid cell division, greater lymph node metastasis, venous and lymphatic invasions, local recurrence, and distant metastasis.4 Although the overall five-year survival of patients with colorectal cancer has improved over the past three decades, the mortality risk of colorectal cancer amongst young adults remains significantly high, even ten years after the diagnosis and with disease free at five years.1 This might be explained by cellular mechanisms of the cancer in young adults that we are yet to understand.
Currently, the invitation to join the Bowel Cancer Screening Programme in the UK is every two years to all men and women aged 60 to 69. This programme would clearly be inadequate for those who are at risk of developing colorectal cancer at an early age. Although it is important to identify modifiable risk factors such as smoking and obesity, clearly those at higher risk need appropriate screening. In addition to this, younger people if at risk need to be convinced of the importance of recognising the risk and seeking medical help at an early stage.
1. Kharazmi E, Fallah M, Sundquist K, Hemminki K. Familial risk of early and late onset cancer: nationwide prospective cohort study. BMJ 2012;345:e8076.
2. Forbes SS, Sutradhar R, Paszat LF, Rabeneck L, Urbach DR, Baxter NN. Long- Term Survival in Young Adults With Colorectal Cancer: A Population-Based Study. Dis Colon Rectum 2010;53:973-8.
3. Singh Y, Vaidya P, Hemandas AK, Singh KP, Khakurel M. Colorectal carcinoma in Nepalese young adults: presentation and outcome. Gan To Kagaku Ryoho 2002;29:223-9.
4. Ko EY, Ha HK, Kim AY, Yoon KH, Yoo CS, Kim HC, et al. CT differentiation of mucinous and nonmucinous colorectal carcinoma. AJR Am J Roentgenol 2007;188(3):785-91.
Competing interests: No competing interests
Re: Familial risk of early and late onset cancer: nationwide prospective cohort study
While discussing weaknesses of their study, Kharazmi E et al. surprisingly omitted the potential of detection bias. The increased risk of concordant cancers among offspring could, at in least in part, be attributable to an increase use of cancer screening by the concerned offspring; offspring whose parents are diagnosed with a specific cancer are more likely to be screened. A positive family history for both patients and primary care physicians is likely to be a screening facilitator, notably when guidelines are unclear (e.g. prostate cancer)[1]. The fact that the highest risks reported by Kharazmi E et al. were related to cancers for which screening tests and/or programs are available supports the potential of detection bias. Also in line with the authors’ findings, the younger the parents are diagnosed, the more likely the offspring might be screened.
Given the increasing concern of overdiagnosis related to screening (e.g prostate cancer)[2], the possibility of detection bias should be explored. At least two approaches can be suggested to the authors. First, if information on the circumstance of cancers detection (screening-detected versus clinically detected cancers) is available, stratified analysis by the type of detection should be conducted. The magnitude of the family risk for clinically detected cancers and screening-detected cancers among the offspring should be presented. 2) If this information is not available, analyses should be conducted by cancer stages (a information likely to be collected in the Swedish Cancer registry). Indeed, screening and its related concept of lead time typically produce cancer stage shift. A higher proportion of cancers at early stages among offspring of parents with cancers than offspring of parents without cancers (or other appropriate reference population) would suggest a meaningful influence of screening on the increased risk reported by Kharazmi E et al.
1. Tudiver F, Guibert R, Haggerty J, Ciampi A, Medved W, et al. What influences family physicians' cancer screening decisions when practice guidelines are unclear or conflicting? J Fam Pract. 2002;51(9):760.
2. Moynihan R, Doust J, Henry D. Preventing overdiagnosis: how to stop harming the healthy BMJ. 2012 28;344:e3502.
Competing interests: No competing interests