Results

The study Cohort
The database relative to the players in series A and B that were born in Italy and actively playing during the period of 1970-2001 includes 7,325 players. For all of the players in the cohort, the date of birth, the football career in series A and/or B including the first year of professional activity, the principal role of the player, the eventual date of death or the status of life during the ultimate days of the follow-up (31 December 2001) were noted. The number of years-overall people during the period of observation, considering the deceased is 137,078.

Observed cases
The total number of ALS cases which arose during period of 1970-2001 among the players from series A or B active during the period of examination is 5. (a sixth case was excluded because the player was born outside of Italy.) The cases are not distributed homogeneously during the period of observation because there were no cases registered during the period of 1970-1979, while there were 2 cases during the period of 1980-1989 and three during the period of 1990-2001. The average age of the onset of ALS was 43.4 years (DS 9.1; range, 33-56) (it should be noted that the sixth case, excluded from the total, had an onset age of 36 years).

Calculation of the SMR

The total number of expected cases during the period of 1970-2001, using as a reference the data from two regional Italian registries, is equal to 0.77. The calculated SRM in as much is equal to 6.49  (i.c. at 95%, 2.10-15.12) (p<0,0001 ). The SMR by age classification is listed in Table 1. A significant increase in the risk of onset of ALS prior to age 49 is observed, while the risk for an age equal to or greater than 50 years is not significantly advanced.
In Table 2, the SMR is reported according to the role of the player.  The SMR for the role of midfielder, equal to 11.0, is significantly increased.  The SMR for the role of defender is increased (4.1) but not in a significant manner.
No cases of ALS among the forwards or goalkeepers were verified.
In Table 3, the SRM for the number of years played as a professional are reported. For a number of years  <6, the risk is increased but not in a significant manner.  For a superior number of years >6, the risk is significantly increased.

Table 1.
SMR for ALS according to age classification

Table 2.
SMR for ALS according to the player’s position

Table 3.
SMR for ALS according to the number of years of activity as a professional football player

Comment

The overall calculated SMR (risk) is significantly increased, indicating that in the cohort examined, there is a definite excess of ALS with respect to expectations.
Moreover, is should be considered that the assessment presented is extremely cautious, both because the reference population utilised (epidemiological registries of Piedmont and Puglia) has incidence rates that are among the highest in the world as well as because the reference registries are referring to a very recent period of time (second half of the ‘90s) in the course of which the incidences of ALS may be increased with respect to the years of the ‘70s and ‘80s.
Furthermore, a systematic research was not implemented among the subjects included in the cohort to exclude the diagnosis of ALS but only for identifying the cases which was based on a series of sources that may not have allowed for identifying all of the cases, above all those arising during the ten-year period of the study. 
The data of this evaluation that confirms the observation of the preliminary study on death certificates, indicated that the excess of risk is above all assigned to the subjects of an age inferior to 50 years, a very young age for ALS, that in the most reliable epidemiological studies presents an average age of onset at between 63 and 65 years.
Moreover, it should be recalled that 10 year average of onset of the five cases included in the study is 43 years.
The excess of risk observed appears to be significant in the period successive to 1980, while no cases were identified in the prior ten-year period.  Very interesting and suggestive is the relationship of quantity-effect verified with a significant increase in the risk only among the subjects that had played as a professional for a period superior to 5 years.  Finally, an increase in risk is observed only among the football players with the position of midfielder.  For the other positions, either the increase in risk is not significant (defender), or the risk is not able to be calculated because no cases were identified. The significance of this observation is uncertain.   
In conclusion, the gathered data indicates that the number of players of professional football that have developed ALS is significantly greater than expected and that there is a quantity-effect trend between the risk of ALS and the number of years played as a professional football player.
The excess of risk observed (6.5) is net superior to the excess of risk generically connected to sporting activity deduced by the metanalysis of the controlled case published in literature (1,4).
This may indirectly indicate that the risk of developing ALS among the professional football players is not exclusively connected to the intense physical activity or to the effect of trauma or micro-trauma but appears specifically connected to the activity of football itself.
At the current time, it is not yet possible to define the nature of the factor/s that determine such risk.  It is possible to develop some hypotheses: (1) contact with substances used such as herbicides or fertilisers on the playing or training fields; (2) use of substances for the purpose of doping or legal pharmaceuticals, eventually with a superior dose or a prolonged period with respect to that normally used by the general population;  (3) metabolic alterations of the muscle or motoneurons correlated to specific methods of training or playing; (4) traumatisms/micro-traumatisms specifically repeated in the game of football.
Also taking into consideration the young age of onset of the major part of the ALS cases among the football players, it could be further hypothesised that the toxic environmental factors responsible for the onset of ALS induces an anticipation in the age of the onset of the disease in subjects that are “genetically” predisposed.

Taken from the book-testimonial "ALS, the drama and the hope"
by Ludovico Perrone.